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Conventional bactericides struggle with biofilm barriers and inefficient deposition on hydrophobic leaves, resulting in undesirable control of plant bacterial diseases. To overcome these challenges, an innovative ferrocene‐based small‐molecule (FccA8R) is conceived, featuring biofilm disruption capabilities. Further optimizing FccA8R with seven‐membered oligosaccharide‐involved host–guest supramolecular strategy creates two kinds of biocompatible multifunctional supramolecular nanospheres (FccA8R@β‐CD and FccA8R@HP‐β‐CD). This manipulation efficiently eradicates mature biofilm barriers while enhancing droplet retention on hydrophobic leaves. At a concentration of 56.64 µg mL−1, the two materials remove Xanthomonas‐biofilms by 76.32–76.83%, notably surpassing that of single FccA8R (57.96%). Their versatility extends to the enhanced inhibition of bacterial motility, extracellular enzymes secretion, and exopolysaccharides production, all reducing the bacterial virulence. In vivo pot experiments, FccA8R@β‐CD and FccA8R@HP‐β‐CD demonstrate workable control efficacies of 48.91–52.03% against rice bacterial blight at 200 µg mL−1, superior to the commercial thiodiazole‐copper‐20%SC (36.42%) and FccA8R‐0.1%Tween (39.54%). Furthermore, these supramolecular assemblies disclose broad‐spectrum bactericidal efficacy (71.45–73.19%) against kiwifruit canker, significantly higher than thiodiazole‐copper‐20%SC (43.05%) and FccA8R‐0.1%Tween (57.24%). Besides, supramolecular bactericides are safe for plants and non‐target organisms like zebrafish and earthworms. Briefly, this research builds a key foundation for creating green bactericides from small‐molecule conception to eco‐friendly supramolecular assemblies, realizing the prevention of bacterial diseases and environmental safety. [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammatory disease caused by bacterial biofilms, which leads to the destruction of periodontal tissue. Current treatments, such as mechanical cleaning and antibiotics, struggle to effectively address the persistent biofilms, inflammation, and tissue damage. A new approach involves developing a Janus nanomotor (J-CeM@Au) by coating cerium dioxide-doped mesoporous silica (CeM) with gold nanoparticles (AuNPs). This nanomotor exhibits thermophoretic motion when exposed to near-infrared (NIR) laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs. The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties, allowing it to penetrate biofilms and kill bacteria. Additionally, the nanomotor's ability to scavenge reactive oxygen species (ROS) can modulate the immune response and create a regenerative environment, promoting the healing of periodontal tissue. Overall, this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.

[Display omitted] • A nanoplatform capable of both self-supplying H 2 O 2 and generating NO is designed to enhance the effectiveness of chemodynamic therapy for biofilm eradication. • The nanoplatform can respond to the acidic microenvironment within biofilms to trigger a cascade of reactions that produce reactive species such as NO, hydroxyl radicals, and peroxynitrite. • The nanoplatform shows remarkable antibiofilm efficacy by dispersing the biofilm and reducing bacterial viability. Bacterial biofilms present a profound challenge to global public health, often resulting in persistent and recurrent infections that resist treatment. Chemodynamic therapy (CDT), leveraging the conversion of hydrogen peroxide (H 2 O 2) to highly reactive hydroxyl radicals (•OH), has shown potential as an antibacterial approach. Nonetheless, CDT struggles to eliminate biofilms due to limited endogenous H 2 O 2 and the protective extracellular polymeric substances (EPS) within biofilms. This study introduces a multifunctional nanoplatform designed to self-supply H 2 O 2 and generate nitric oxide (NO) to overcome these hurdles. The nanoplatform comprises calcium peroxide (CaO 2) for sustained H 2 O 2 production, a copper-based metal–organic framework (HKUST-1) encapsulating CaO 2 , and l -arginine (l -Arg) as a natural NO donor. When exposed to the acidic microenvironment within biofilms, the HKUST-1 layer decomposes, releasing Cu2+ ions and l -Arg, and exposing the CaO 2 core to initiate a cascade of reactions producing reactive species such as H 2 O 2 , •OH, and superoxide anions (•O 2 –). Subsequently, H 2 O 2 catalyzes l -Arg to produce NO, which disperses the biofilm and reacts with •O 2 – to form peroxynitrite, synergistically eradicating bacteria with •OH. In vitro assays demonstrated the nanoplatform's remarkable antibiofilm efficacy against both Gram-positive Methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa , significantly reducing bacterial viability and EPS content. In vivo mouse model experiments validated the nanoplatform's effectiveness in eliminating biofilms and promoting infected wound healing without adverse effects. This study represents a breakthrough in overcoming traditional CDT limitations by integrating self-supplied H 2 O 2 with NO's biofilm-disrupting capabilities, offering a promising therapeutic strategy for biofilm-associated infection. [ABSTRACT FROM AUTHOR]

Aims The aim of this work was to evaluate the efficacy of an organosilicon-based, commercially available antimicrobial formulation in the My-shield® product line against bacterial surface contamination. Methods and results The antimicrobial product was tested in vitro for its long-term persistence on surfaces and effectiveness against Staphylococcus aureus biofilms in comparison to 70% ethanol and 0.1% or 0.6% sodium hypochlorite. Field testing was also conducted over 6 weeks at a university athletic facility. In vitro studies demonstrated the log reductions achieved by the test product, 70% ethanol, and 0.1% sodium hypochlorite were 3.6, 3.1, and 3.2, respectively. The test product persisted on surfaces after washing and scrubbing, and pre-treatment with this product prevented S. aureus surface colonization for up to 30 days. In comparison, pre-treatment with 70% ethanol or 0.6% sodium hypochlorite was not protective against S. aureus biofilm formation after seven days. The field test demonstrated that weekly applications of the test product were more effective at reducing surface bacterial load than daily applications of a control product. Conclusions The test product conferred greater long-term protection against bacterial growth and biofilm formation by S. aureus than ethanol and sodium hypochlorite. Even with less frequent applications, the test product maintained a high level of antimicrobial activity. [ABSTRACT FROM AUTHOR]

AbstractBiofilms represent resilient microbial communities responsible for inducing chronic infections in human subjects. Given the escalating challenges associated with antibiotic therapy failures in clinical infections linked to biofilm formation, a peptide-based approach emerges as a promising alternative to effectively combat these notoriously resistant biofilms. Contrary to conventional antimicrobial peptides, which predominantly target cellular membranes, antibiofilm peptides necessitate a multifaceted approach, addressing various "biofilm-specific factors." These factors encompass Extracellular Polymeric Substance (EPS) degradation, membrane targeting, cell signaling, and regulatory mechanisms. Recent research endeavors have been directed toward assessing the potential of peptides as potent antibiofilm agents. However, to translate these peptides into viable clinical applications, several critical considerations must be meticulously evaluated during the peptide design process. This review serves to furnish an all-encompassing summary of the pivotal factors and parameters that necessitate contemplation for the successful development of an efficacious antibiofilm peptide. [ABSTRACT FROM AUTHOR]

Biofilms, particularly those formed by multiple bacterial species, pose significant economic and environmental challenges, especially in the context of medical implants. Addressing the urgent need for effective treatment strategies that do not exacerbate drug resistance, we developed a novel nanoformulation, Ce6&PMb@BPN, based on black phosphorus nanosheets (BPN) for targeted treatment of mixed-species biofilms formed by Acinetobacter baumannii (A. baumannii) and methicillin-resistant Staphylococcus aureus (MRSA).The formulation leverages polymyxin B (PMb) for bacterial targeting and chlorin e6 (Ce6) for photodynamic action. Upon near-infrared (NIR) irradiation, Ce6&PMb@BPN efficiently eliminates biofilms by combining chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), reducing biofilm biomass significantly within 30 min. In vivo studies on mice infected with mixed-species biofilm-coated catheters demonstrated the formulation's potent antibacterial and biofilm ablation effects. Moreover, comprehensive biosafety evaluations confirmed the excellent biocompatibility of Ce6&PMb@BPN. Taken together, this intelligently designed nanoformulation holds potential for effectively treating biofilm-associated infections, addressing the urgent need for strategies to combat antibiotic-resistant biofilms, particularly mixed-species biofilm, in medical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of wound infections, often progressing into serious invasive bloodstream infections. MRSA disproportionately affects Indigenous peoples in Canada with higher rates of skin and wound infections, an example of persistent gaps in health outcomes between Indigenous and non-Indigenous peoples precipitated by the legacy of colonialism. Conversely, Indigenous peoples have long used natural remedies for infections and other diseases; however, their knowledge was rarely considered for modern medicine. The stagnant antibiotic discovery pipeline and alarming rise of resistance to current antibiotics prompted us to turn to Indigenous medicine as an untapped source of antimicrobials. As such, we collected and prepared 85 extracts of medicinal plants of value to Indigenous peoples spanning the Canadian Prairies. We explored the antimicrobial potential of these extracts against MRSA under wound infection-mimetic conditions compared with culture media typically used to study bacterial antibiotic responses and biofilms but not adequately representative of infection sites. We identified extracts with MRSA growth inhibitory [e.g., bergamot, dock, gaillardia, and dandelion extracts] and biofilm prevention and eradication [e.g., gumweed extracts] activities. Extracts, including those of chokecherry, hoary puccoon, and Northern bedstraw, were only active under wound infection-mimetic conditions, highlighting the benefit of antibiotic discovery under host-relevant conditions. Testing growth inhibitory extracts against an S. aureus cross-resistance platform suggested that they act through mechanisms likely distinct from known antibiotic classes. Together, through an interdisciplinary partnership leveraging Western approaches and traditional Indigenous knowledge, we identified plant extracts with promising antimicrobial potential for drug-resistant MRSA wound infections.IMPORTANCEWe explored the antimicrobial potential of traditional Indigenous remedies against MRSA under wound infection-mimetic conditions. We chose to tackle MRSA wound infections because they constitute an Indigenous health priority, ensuring mutual benefits and reciprocity, which are important principles in partnerships between Indigenous and non-Indigenous researchers. Our partnerships strive to serve as steps towards reconciliation with Indigenous peoples in Canada and a roadmap inspiring similar interdisciplinary collaborations to tackle other healthcare priorities. We identified extracts with promising antibacterial growth inhibitory, biofilm prevention, and eradication activities against MRSA. The antimicrobial potential of some extracts was only observed under wound infection-mimetic conditions, a proof-of-concept that screening under infection-mimetic conditions reveals novel activity undetected under standard conditions. The natural product antimicrobial extracts discovered herein warrant further investigation into their mode of action and chemical composition; they may address the dire need for new antimicrobial and anti-biofilm activity to counter the AMR crisis.

Bacterial biofilms present a significant challenge in treating drug-resistant infections, necessitating the development of innovative nanomedicines. In this study, we introduce triclosan-conjugated, lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery platform. The micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization of ε-caprolactone (CL) and triclosan-containing cyclic trimethylene carbonate (MTC-Tri). Poly(ethylene glycol) (PEG-OH) acted as the macro-initiator, resulting in micelles with a PEG shell that facilitated their penetration into bacterial biofilms. An important advantage of our micelles lies in their interaction with local bacterial lipases within biofilms. These lipases triggered rapid micelle degradation, releasing triclosan in a controlled manner. This liberated triclosan effectively eliminated bacteria embedded in the biofilms. Notably, the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts, indicating their biocompatibility and safety. This finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial biofilms. Our triclosan-conjugated, lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial biofilms. By harnessing biofilm properties and implementing a responsive drug delivery system, we seek to provide an effective solution in the fight against drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Recurrent bacterial infections, impenetrable microbial biofilms, and irremediable antibiotic resistance are the most perilous threats in orthopedic implant‐associated infections (IAIs). Recently, chemodynamic therapy (CDT) has been considered a promising therapy, while the clinical practices for existing CDT agents are limited by the low therapeutic efficiency in physiological circumstances. Herein, it is demonstrated that silica‐copper nanosheets (Si@Cu NSs) exhibit a combined therapeutic photothermal‐chemodynamic strategy for IAIs treatment with superior capacity and biocompatibility. This unique design endows the nanostructure with enhanced copper‐based Fenton‐like properties via p‐d orbital hybridization by incorporating copper nanoclusters (Cu NCs) on silicene nanosheets (Si NSs) matrix, integrating inherent photothermal performance of Si NSs with specific catalytic anti‐infection of Cu NCs against planktonic bacteria and biofilms both in vitro and in vivo. This study not only reveals the promising bio‐application prospects of 2D nanocatalytic biomaterials but also demonstrates the feasibility of constructing novel CDT agents by orbital hybridization for the catalytic treatment of IAIs. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 µg/mL, MBC = 8 µg/mL) and its persistent biofilms (=99%, MBEC = 8 µg/mL). TFBZ manifested significant irreversible timedependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections. [ABSTRACT FROM AUTHOR]

Cobaloximes of the type [Co(X)(dmgH)2B], where dmgH = Dimethylglyoxime monoanion, X = Cl−, Br−, SCN− and B = 4-Aminophenylacetic acid (4-APAA) and4-Aminobenzoic acid (4-ABA), have been synthesized. Better yield was obtained when bromide ion was used as an axial ligand. The synthesized cobaloximes were characterized by IR, UV spectroscopy and cyclic voltammetry. The structures of the two cobaloximes [Co(Cl)(dmgH)2(4-ABA)] and [Co(Br)(dmgH)2(4-ABA)] have been characterized by X-ray Crystallography. The complexes were screened for their antibacterial activity against gram positive Methicillin Resistant Staphylococcus aureus (MRSA) MTCC 1430 and gram negative Acinetobacter baumannii MTCC 1425 bacteria using Agar well diffusion method, Tube method and Biofilm eradication on biomaterial methods. It has been found that all the cobaloxime complexes exhibited inhibition against both the test microorganisms. Cobaloximes have been found to be more active against the gram negative bacteria compared to gram positive bacteria. [ABSTRACT FROM AUTHOR]

Fomes fomentarius and Daedaleopsis tricolor produced significant amounts of water-insoluble melanins, and our previous study successfully enhanced their water solubility by arginine modification. This research aimed to investigate the anti-ultraviolet, antibacterial, and biofilm eradication activities of both the melanins and arginine-modified melanin (melanin derivatives) from these two fungi against an acne-causing bacterium (Cutibacterium acnes). Apart from these, the cytotoxicity of the melanins and melanin derivatives on human skin cells was also evaluated. Melanin derivatives of both two fungi showed significantly higher antibacterial and biofilm eradication activities compared with their original forms. Specifically, the MIC50 values of the melanin derivatives (1,000 μg/mL) are the same as those of erythromycin. Regarding biofilm eradication capacity, the MBEC50 value of D. tricolor melanin derivative (250 μg/mL) was just half of both erythromycin and F. fomentarius melanin derivative. However, it required a 2-fold higher concentration of melanin derivatives than erythromycin to inhibit 90% of the bacterial population and eradicate 90% of their biofilm. Regarding anti-ultraviolet activity, blending melanins or melanin derivatives with a moisturizer/sunscreen enhanced their UV light absorption and the sun protection factor (SPF) values. In addition, melanins showed better effects than their derivatives, and those of D. tricolor were better than F. fomentarius. Remarkably, adding D. tricolor melanin (10%) to a Nivea pure cream could turn this cream into a broad-spectrum sunscreen, with its SPF value and critical wavelength increasing from 7.74 and 338.67 to 14.02 and 377.0, respectively. In addition, adding melanin or a melanin derivative of D. tricolor to an Olay sunscreen enhanced the SPF and the critical wavelength of the sunscreen from 17.25 and 371.67 to 23.82 and 374 and 23.38 and 372, respectively. Notably, melanins and melanin derivatives showed no toxicity in human fibroblasts. The obtained data suggest that arginine modification significantly enhanced the antibacterial and biofilm eradication activities of melanins from D. tricolor and F. fomentarius. However, this is not the case when it comes to their anti-ultraviolet activities. In addition, melanin and melanin derivatives from D. tricolor are potential candidates for anti-acne sunscreen products and are worth further investigation. [ABSTRACT FROM AUTHOR]

Fomes fomentarius and Daedaleopsis tricolor produced significant amounts of water-insoluble melanins, and our previous study successfully enhanced their water solubility by arginine modification. This research aimed to investigate the anti-ultraviolet, antibacterial, and biofilm eradication activities of both the melanins and arginine-modified melanin (melanin derivatives) from these two fungi against an acne-causing bacterium (Cutibacterium acnes). Apart from these, the cytotoxicity of the melanins and melanin derivatives on human skin cells was also evaluated. Melanin derivatives of both two fungi showed significantly higher antibacterial and biofilm eradication activities compared with their original forms. Specifically, the MIC50 values of the melanin derivatives (1,000 μg/mL) are the same as those of erythromycin. Regarding biofilm eradication capacity, the MBEC50 value of D. tricolor melanin derivative (250 μg/mL) was just half of both erythromycin and F. fomentarius melanin derivative. However, it required a 2-fold higher concentration of melanin derivatives than erythromycin to inhibit 90% of the bacterial population and eradicate 90% of their biofilm. Regarding anti-ultraviolet activity, blending melanins or melanin derivatives with a moisturizer/sunscreen enhanced their UV light absorption and the sun protection factor (SPF) values. In addition, melanins showed better effects than their derivatives, and those of D. tricolor were better than F. fomentarius. Remarkably, adding D. tricolor melanin (10%) to a Nivea pure cream could turn this cream into a broad-spectrum sunscreen, with its SPF value and critical wavelength increasing from 7.74 and 338.67 to 14.02 and 377.0, respectively. In addition, adding melanin or a melanin derivative of D. tricolor to an Olay sunscreen enhanced the SPF and the critical wavelength of the sunscreen from 17.25 and 371.67 to 23.82 and 374 and 23.38 and 372, respectively. Notably, melanins and melanin derivatives showed no toxicity in human fibroblasts. The obtained data suggest that arginine modification significantly enhanced the antibacterial and biofilm eradication activities of melanins from D. tricolor and F. fomentarius. However, this is not the case when it comes to their anti-ultraviolet activities. In addition, melanin and melanin derivatives from D. tricolor are potential candidates for anti-acne sunscreen products and are worth further investigation.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health concern. The propensity of MRSA to form biofilms is a significant contributor to its pathogenicity. Strategies to treat biofilms often involve small molecules that disperse the biofilm into planktonic cells. Linezolid and, by extension, theoxazolidinones have been developed to treat infections caused by Gram-positive bacteria such as MRSA. However, the clinical development of these antibiotics has mainly assessed the susceptibility of planktonic cells to the drug. Previous studies evaluating the anti-biofilm activity of theoxazolidinones have mainly focused on the biofilm inhibition of Enterococcus faecalis and methicillin-sensitive Staphylococcus aureus, with only a few studies investigating the activity of oxazolidinones for eradicating established biofilms for these species. Very little is known about the ability of oxazolidinones to eradicate MRSA biofilms. In this work, five oxazolidinones were assessed against MRSA biofilms using a minimum biofilm eradication concentration (MBEC) assay. All oxazolidinones had inherent antibiofilm activity. However, only ranbezolid could completely eradicate MRSA biofilms at clinically relevant concentrations. The susceptibility of the MRSA biofilms to ranbezolid was synergistically enhanced by coadministration with the nitroxide biofilm dispersal agent C-TEMPO. We presume that ranbezolid acts as a dual warhead drug, which combines the mechanism of action of the oxazolidinones with a nitric oxide donor or cytotoxic drug. [ABSTRACT FROM AUTHOR]

Periodontitis is a biofilm-related disease characterized by damage to the periodontal tissue and the development of systemic diseases. However, treatment of periodontitis remains unsatisfactory, especially with deep-tissue infections. This study describes rationally designed multifunctional photothermocatalytic agents for near-infrared-II light-mediated synergistic antibiofilm treatment, through modification of Lu-Bi 2 Te 3 with Fe 3 O 4 and poly(ethylene glycol)-b-poly(l-arginine) (PEG- b -PArg). Notably, 1064-nm laser irradiation led to photothermal/thermocatalytic effects, resulting in the synergistic generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consequent damage to the biofilm. This treatment was based on the thermoelectric and photothermal conversion properties of Lu-Bi 2 Te 3 , the peroxidase-like catalytic capacity of Fe 3 O 4 , and the guanidinium polymer, PEG- b -PArg. Oxidative damage to biofilm was further enhanced by H 2 O 2 , resulting in the effective elimination of biofilm both in vitro and in vivo. These findings suggest that this synergistic therapeutic strategy is effective for the clinical treatment of periodontitis. The current treatment for periodontitis involves time-consuming and labor-intensive clinical scaling of the teeth. The present study is the first to assess the efficacy of a photothermal catalyst for periodontitis treatment. This used near-infrared-II light at 1064 nm to induce oxidative damage in the biofilm, resulting in its degradation. The synergistic photothermal/thermoelectric effect produced deep tissue penetration and was well tolerated, and can kill the biofilm formed by periodontitis pathogens up to 5 orders of magnitude, effectively treating the biofilm-induced periodontitis. [Display omitted] [ABSTRACT FROM AUTHOR]

One of the serious threats to global public health is the bacterial biofilm, which results in numerous persistent and recurrent infections. Herein, we proposed a near-infrared (NIR) light-triggered "nano-domino" system with "dispersing and killing" functionality for biofilm eradication. The nanoplatform was fabricated by the self-assembly of chitosan conjugated with L-arginine (L-Arg, a natural nitric oxide (NO) donor) and indocyanine green (ICG, a phototherapy agent). Using an NIR irradiation "trigger", a series of reactive oxygen species (ROS) including singlet oxygen (1O 2), hydrogen peroxide (H 2 O 2), and superoxide anions (·O 2 −), as well as heat were generated from ICG aggregates. Subsequently, 1O 2 and H 2 O 2 catalyzed L-Arg to produce NO, which dispersed the biofilm and reacted with ·O 2 − to form peroxynitrite to kill bacteria with ROS collaboratively. Meanwhile, the generated heat increased the permeability of bacterial membranes, aggravating the damage to biofilm bacteria. The experiments on biofilm eradication demonstrated that this "nano-domino" system was capable to eradicate over 99.99% of biofilms formed by Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa under 5-min NIR irradiation. Notably, these integrated benefits allowed the system to promote the healing of MRSA biofilm-infected wounds in vivo with negligible toxicity. Overall, this reported NIR-triggered "nano-domino" system holds great promise for addressing the difficulties associated with bacterial biofilm eradication. Novel agents for biofilm eradication are urgently needed due to the alarming rise in antimicrobial resistance to conventional antibiotics and the critical shortage of new drugs. In this study, we created a nano-domino system that uses near-infrared (NIR) light as a trigger to eradicate mature biofilms. In response to a short-term NIR irradiation, the proposed nanoplatform could generate nitric oxide and peroxynitrite to disperse the biofilm and kill the bacteria inside, respectively, leading to efficient eradication of Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms with minimal cytotoxicity. The findings, therefore, indicate that this nanoplatform with enhanced antibiofilm performance might provide a reliable and promising solution to biofilm-related problems. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Enterococci participate in cheese production, either spontaneously or when added to milk as starter cultures. These bacteria contribute to the development of the flavor, aroma, and texture of the cheese, as well as to its preservation. Despite their potential, some strains of E. faecium and E. faecalis, normal inhabitants of the intestinal tract, can cause infections. Therefore, their presence in food and water has been used as an indicator of fecal contamination. The results presented here show high levels of resistance to the antibiotic vancomycin and multidrug resistance. Some of these strains had virulence genes. These same enterococci were also capable of producing biofilms resistant to the disinfectant benzalkonium chloride. These findings highlight the potential risk of the presence of E. faecium and E. faecalis in cheese and the importance of implementing efficient control measures to guarantee the safety of dairy products. This study aimed to investigate enterococci recovered from eight Portuguese cheeses made with raw ewe's milk, regarding antibiotic resistance, virulence genes, minimum inhibitory concentration (MIC) of benzalkonium chloride (BAC), biofilm formation capacity, and biofilm eradication (MBEC) by BAC. Antimicrobial resistance against seven antibiotics of five groups was evaluated using the disk diffusion method. The presence of the genes that encode resistance to the antibiotics penicillin (blaZ), erythromycin (ermA, ermB, and ermC), vancomycin (vanA and vanB), aminoglycoside (aac(6′)-Ie-aph(2″)-Ia), and β-lactam (pbp5) and the genes that encode virulence factors, frsB, cylA, gelE, esp, and agg, were investigated via multiplex PCR. The susceptibility of planktonic cells to BAC was evaluated by the MIC and MBC values of the isolates, using the broth microdilution method. To assess the biofilm-forming ability and resistance of biofilms to BAC, biofilms were produced on stainless steel coupons, followed by exposure to BAC. The results showed a high resistance to the antibiotics vancomycin (87.5%), erythromycin (75%), tetracycline (50%), and penicillin (37.5%). Multidrug resistance was observed in 68.8% of the isolates. Genes encoding the virulence factors FrsB (frsB) and gelatinase E (gelE) were detected in all isolates. The esp and cylA genes were found in 56.3% and 37.5% of the isolates, respectively. All isolates exhibited a biofilm-forming ability, regardless of incubation time and temperature tested. However, after 72 h at 37 °C, E. faecium and E. faecalis biofilms showed significant differences (p ≤ 0.05). Although most isolates (62.5%) were susceptible to BAC (MIC ≤ 10 mg/L), biofilms of the same isolates were, generally, resistant to the higher concentration of BAC (80 mg/mL) tested. This study using Enterococcus isolates from a ready-to-eat food, such as cheese, reveals the high percentages of vancomycin resistance and multidrug resistance, associated with the presence of virulence genes, in isolates also capable of producing biofilms resistant to BAC, an important active ingredient of many disinfectants. These results emphasize the need for effective control measures to ensure the safety and quality of dairy products. [ABSTRACT FROM AUTHOR]

Aims: The use of phytochemicals to improve the effectiveness of antibiotics is a promising strategy for the development of novel antimicrobials. In this study, the antibiofilm activity of perillyl alcohol and hydrocinnamic acid, both phytochemicals present in several plants, and two antibiotics from different classes (amoxicillin and chloramphenicol) was tested, alone and in combination, against Escherichia coli. Methods and results: Each molecule was tested at the minimum inhibitory concentration (MIC), 5 × MIC, and 10 × MIC, and characterized concerning biomass removal, metabolic inactivation, and cellular culturability. The highest percentages of metabolic inactivation (88.5% for 10 × MIC) and biomass reduction (61.7% for 10 × MIC) were obtained with amoxicillin. Interestingly, for 5 × MIC and 10 × MIC, phytochemicals provided a total reduction of colony-forming units (CFUs). Dual and triple combinations of phytochemicals and antibiotics (at MIC and 5 × MIC) demonstrated high efficacy in metabolic inactivation, moderate efficacy in terms of biomass reduction, and total reduction of cellular culturability for 5 × MIC. Conclusions: The results demonstrated the antibiofilm potential of phytochemicals, highlighting the advantage of phytochemical/antibiotic combinations for biofilm control. [ABSTRACT FROM AUTHOR]

European Union (EU) countries strive to improve the quality and safety of food of animal origin. Food production depends on a good microbiological quality of fodder. However, feed can be a reservoir or vector of pathogenic microorganisms, including Salmonella or Escherichia coli bacteria. Salmonella spp. and E. coli are the two most important food-borne pathogens of public health concern. Contamination with these pathogens, mainly in the poultry sector, can lead to serious food-borne diseases. Both microorganisms can form biofilms on abiotic and biotic surfaces. The cells that form biofilms are less sensitive to disinfectants, which in turn makes it difficult to eliminate them from various surfaces. Because the usage of formaldehyde in animal feed is prohibited in European countries, the replacement of this antibacterial with natural plant products seems very promising. This study aimed to assess the inhibitory effectiveness of Vaccinium vitis-idaea extract against biofilm produced by model Salmonella enterica and E. coli strains. We found that formaldehyde could effectively kill both species of bacterial cells in biofilm, while the lingonberry extract showed some antibiofilm effect on S. enterica serovar Senftenberg. In conclusion, finding natural plant products that are effective against biofilms formed by Gram-negative bacteria is still challenging. [ABSTRACT FROM AUTHOR]

The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties. [ABSTRACT FROM AUTHOR]

Biofilms are the primary source of contamination linked to nosocomial infections by promoting bacterial resistance to antimicrobial agents, including disinfectants. Using essential oils, this study aims to inhibit and eradicate the biofilm of enterobacteria and staphylococci responsible for nosocomial infections at Guelma Hospital, northeastern Algeria. Thymbra capitata, Thymus pallescens and Artemesia herba-alba essential oils were evaluated against clinical strains of Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The antimicrobial activity of the essential oils under consideration was assessed using an agar disc diffusion assay and the determination of minimum inhibitory concentrations (MICs). In addition, the crystal violet method and scanning electron microscopy (SEM) evaluated biofilm inhibition and eradication by those antimicrobial agents. The results indicate that T. pallescens essential oil was the most effective antimicrobial agent against pathogenic bacteria, with large zones of inhibition (up to 50 mm against S. aureus), low MICs (0.16 to 0.63 mg/mL), and powerful biofilm eradication up to 0.16 mg/mL in both 24 h and 60-min exposure times. Thus, Algerian thyme and oregano could be used in various ways to combat the biofilm that causes nosocomial infection in local hospitals. [ABSTRACT FROM AUTHOR]

Background: Pyocyanin is a secondary metabolite secreted by P. aeruginosa. It is a redox-active blue/green phenazine pigment that has various beneficial applications. The present study aims at screening the production of pyocyanin among clinical and environmental P. aeruginosa isolates in Dakahlya governorate, Egypt. Thereafter, large-scale production, purification, structure elucidation, and assessment of the biological activity of the highest pyocyanin producers were targeted. Results: Pyocyanin from the highest clinical (PsC05) and environmental (PsE02) producers were subjected to large-scale production, followed by purification using silica gel column. Pyocyanin was characterized using TLC, UV-Vis, 1 H NMR, and FTIR spectroscopy to confirm its structure and purity. Purified pyocyanin showed remarkable antimicrobial efficacy against all tested food-borne pathogens, MDR/XDR clinically isolated bacteria and C. albicans. Furthermore, it showed a substantial effect on biofilm inhibition and eradication of pre-formed biofilm against strong biofilm producing bacterial pathogens. However, it had limited antibiofilm activity against C. albicans. Pyocyanin from PsC05 had higher antioxidant and radicals scavenging activity than that from PsE02 as determined by FRAP, DPPH, and ABTS assays. Likewise, pyocyanin from PsC05 was more active against tested cancer cell lines, especially human Breast Cancer (MCF-7) and Colorectal Carcinoma (HCT-116), than that from PsE02. More importantly, it showed minimal cytotoxicity to normal cells. Conclusions: P. aeruginosa clinical and environmental isolates produce pyocyanin pigment in varying amounts. Pyocyanin exhibits substantial anti-bacterial, and anti-fungal activity; thus, enhancing its medical applicability. It could be used to inhibit and/or eradicate biofilm from the surfaces of medical devices which is a chief source of nosocomial infections. Its antioxidant along with cytotoxic activity against cancer cell lines, make it a promising contender for use as a substitute for synthetic agents in cancer treatment. [ABSTRACT FROM AUTHOR]

Aims We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain. Methods and results PgTeL showed a minimum inhibitory concentration of 172.0 μg ml−1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0–256.0 μg ml−1 reduced biofilm biomass by 31.0%–64.0%. Furthermore, 32.0–256.0 μg ml−1 PgTeL decreased the metabolic activity of the biofilm by 32.0%–93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0–256.0 μg ml−1, PgTeL reduced metabolic activity in C. neoformans by 36.0%–92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions. Conclusions PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent. [ABSTRACT FROM AUTHOR]

Cholinium-based ionic liquids are compounds increasingly studied in pharmaceutics and biomedicine to enhance bioavailability in drug delivery systems and as bioactive ingredients in pharmaceutical formulations. However, their potential as antimicrobial agents has scarcely been investigated. Herein, we explored the antimicrobial activity of a series of surface-active cholinium-based ionic liquids (Chol-ILs). For this purpose, Chol-ILs with alkyl chains of 10–16 carbon atoms were synthesized and their self-assembly in aqueous medium was investigated. Subsequently, their antimicrobial activity against a panel of clinically relevant bacteria and their ability to eradicate MRSA and P. aeruginosa PAO1 biofilms was evaluated. Finally, we analyzed the ecotoxicological profile of Chol-ILs in terms of susceptibility to aerobic biodegradation and acute aquatic toxicity against D. magna and V. fisheri. Our results reveal that cholinium-based ILs with alkyl chain lengths ≥12 C show a broad spectrum of antibacterial activity. Their antimicrobial efficacy depends on their hydrophobicity, with the C14–C16 homologs being the most effective compounds. These ILs exhibit antimicrobial activity similar to that of imidazolium ILs and quaternary ammonium antiseptics. Moreover, the longer alkyl chain Chol-ILs are able to eradicate established biofilms at concentrations as low as 16–32 µg/mL. The biodegradation rate of cholinium-based ILs decreases with alkyl chain elongation. Our results reinforce the suitability of Chol-ILs as promising multifunctional compounds for application in pharmaceutical and biomedical formulation. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant Acinetobacter baumannii infections among patients in hospital settings are rising at an alarming rate. The World Health Organization has designated carbapenem-resistant A. baumannii as a priority pathogen for drug discovery. Based on the open drug discovery approach, we screened 400 compounds provided as a Pandemic Response Box by MMV and DNDi to identify compounds with antibacterial and antibiofilm activity against two A. baumannii reference strains using a highly robust resazurin assay. In vitro screening identified thirty compounds with MIC ≤ 50μM having growth inhibitory properties against the planktonic state. Five compounds, with MMV IDs MMV396785, MMV1578568, MMV1578574, MMV1578564, and MMV1579850, were able to reduce metabolically active cells in the biofilm state. Of these five compounds, MMV396785 showed potential antibacterial and antibiofilm activity with MIC, MBIC, and MBEC of 3.125 μM, 12.5, and 25–100 µM against tested A. baumannii strains, respectively, showing biofilm formation inhibition by 93% and eradication of pre-formed biofilms by 60–77.4%. In addition, MMV396785 showed a drastic reduction in the surface area and thickness of biofilms. Further investigations at the molecular level by qRT-PCR revealed the downregulation of biofilm-associated genes when exposed to 50 µM MMV396785 in all tested strains. This study identified the novel compound MMV396785 as showing potential in vitro antibacterial and antibiofilm efficacy against A. baumannii. [ABSTRACT FROM AUTHOR]

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.

Biofilms of sporeformers found in the dairy industry are the major contaminants during processing, as they withstand heat and chemical treatment that are used to control microbes. The present work is aimed to remove these resistant forms of bacterial community (biofilm) present in dairy production lines using ecofriendly agents based on proteinase K (Prot-K) coupled with Zinc oxide nanoparticles (ZnO-NPs). Some metal/metal oxide (Ag, CuO and ZnO) NPs were prepared microbially, and ZnO-NPs were characterized as the most effective ones among them. The produced ZnO-NPs were 15–25 nm in size with spherical shape, and FTIR analysis confirmed the presence of proteins and alkanes surrounding particles as capping agents. Application of Prot-K for eradication (removal) of a model biofilm of mixed sporeformers on food-grade stainless steel resulted in an 83% reduction in the absorbance of crystal violet-stained biofilm. When Prot-K was mixed with the biosynthesized NPs ZnO_G240, the reduction increased to 99.19%. This finding could contribute to an efficient cleaning approach combined with CIP to remove the recalcitrant biofilms in dairy production lines.

Bacterial infections exacerbate the formation of bacterial biofilms, leading to resistance to traditional drugs, persistent infection, and even threatening patient's life. Efficient antimicrobial materials against drug-resistant bacterial biofilms are highly desired. In this study, a photodynamic nanodrug with bacterial targeting was constructed by cooperative coordination of zinc ion with an antimicrobial peptide with hydrophobic tripeptides on the side chains and the photosensitizer chlorin e6. The supramolecular nanodrug with a uniform spherical structure possessed high photosensitizer loading capacity and enhanced photodynamic efficacy, which could deep penetrate and eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms upon 655 nm laser irradiation. Furthermore, in vivo experiments verified the efficient elimination of MRSA biofilms on implanted catheters. This study provides a novel strategy to fabricate metalloprotein-inspired supramolecular photodynamic nanodrugs against drug-resistant bacterial biofilms-associated infections in vivo. [ABSTRACT FROM AUTHOR]

Aim: This work aimed to synthesize magnesium-doped zinc oxide, silver and gold nanoparticles (Nps) and to evaluate their potential to prevent and eradicate Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa biofilms. Materials & methods: The Nps were synthesized by precipitation and metallic reduction techniques. Physicochemical and biological characterization of Nps was performed. Results: All the Nps tested were able to inhibit the formation of E. coli, P. mirabilis, S. aureus and A. baumannii biofilms. The effects on the eradication of preformed biofilms were variable, although all the Nps tested were able to eradicate A. baumannii biofilms. Conclusion: The observed effects make the Nps suitable for coating surfaces and/or antibiotic carriers with medical interest. [ABSTRACT FROM AUTHOR]

Bacterial biofilms generally contribute to chronic infections, including wound infections. Due to the antibiotic resistance mechanisms protecting bacteria living in the biofilm, they are a serious problem in the wound healing process. To accelerate the wound healing process and avoid bacterial infection, it is necessary to select the appropriate dressing material. In this study, the promising therapeutic properties of alginate lyase (AlgL) immobilised on BC membranes for protecting wounds from Pseudomonas aeruginosa infection were investigated. The AlgL was immobilised on never dried BC pellicles via physical adsorption. The maximum adsorption capacity of AlgL was 6.0 mg/g of dry BC, and the equilibrium was reached after 2 h. The adsorption kinetics was studied, and it has been proven that the adsorption was consistent with Langmuir isotherm. In addition, the impact of enzyme immobilisation on bacterial biofilm stability and the effect of simultaneous immobilisation of AlgL and gentamicin on the viability of bacterial cells was investigated. The obtained results showed that the AlgL immobilisation significantly reduced the amount of polysaccharides component of the P. aeruginosa biofilm. Moreover, the biofilm disruption by AlgL immobilised on BC membranes exhibited synergism with the gentamicin, resulting in 86.5% more dead P. aeruginosa PAO-1 cells. [ABSTRACT FROM AUTHOR]

Lactoferrin is an innate glycoprotein with broad antibacterial and antibiofilm properties. The autonomous antibiofilm activity of lactoferrin against Gram-positive bacteria is postulated to involve the cell wall and biofilm components. Thus, the prevention of biomass formation and eradication of preformed biofilms by lactoferrin was investigated using a methicillin-resistant Staphylococcus epidermidis (MRSE) strain. Additionally, the ability of lactoferrin to modulate the expression of the biofilm-associated protein gene (bap) was studied. The bap gene regulates the production of biofilm-associated proteins responsible for bacterial adhesion and aggregation. In the in vitro biofilm assays, lactoferrin prevented biofilm formation and eradicated established biofilms for up to 24 and 72 h, respectively. Extensive eradication of MRSE biofilm biomass was accompanied by the significant upregulation of bap gene expression. These data suggest the interaction of lactoferrin with the biofilm components and cell wall of MRSE, including the biofilm-associated protein. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that offer protection and safe hiding, allowing bacteria to evade host defenses and hide from the reach of antibiotics. Inside biofilm communities, bacteria show an increased rate of horizontal gene transfer and exchange of resistance and virulence genes. Additionally, bacterial communication within the biofilm allows them to orchestrate the expression of virulence genes, which further cements the infestation and increases the invasiveness of the infection. These facts stress the necessity of continuously updating our information and understanding of the etiology, pathogenesis, and eradication methods of this growing public health concern. This review seeks to understand the role of biofilm formation in recurrent urinary tact infections by outlining the mechanisms underlying biofilm formation in different uropathogens, in addition to shedding light on some biofilm eradication strategies. [ABSTRACT FROM AUTHOR]

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds. GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel released nanoparticles for biofilm penetration and eradication, followed by efficient bacteria killing and long-term repair promotion, which achieved a phased treatment to chronic wound. [Display omitted] [ABSTRACT FROM AUTHOR]

Candida auris is a rapidly spreading virulent pathogen frequently resistant to multiple antifungal drugs that can form biofilms and infect wounds. Hence, there is a need for C. auris wound treatments not posing risks for developing antifungal resistance. We tested the ability of a polygalacturonic and caprylic acid ointment (PG+CAP) to rapidly eradicate C. auris biofilms within 2-hour exposures in an in vitro model. Medical-grade honey (MediHoney) wound ointment was used as a comparator. Nine different C. auris strains were tested. PG+CAP eradicated biofilms of 8 of the 9 tested strains and produced a > 5-log 10 reduction of the ninth. MediHoney produced reductions ranging from 2 to 4 log 10 without fully eradicating any strains. The differences between PG+CAP and MediHoney were statistically significant (p < 0.05). These results suggest that PG+CAP is a promising antimicrobial ointment warranting further in vivo study in wounds which may be colonized by C. auris biofilms. [ABSTRACT FROM AUTHOR]

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as β-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with β-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 μg/ml) and β-Glucosidase (112.5 ± 17.6 μg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 μg/ml). Notably, treatment with β-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or β-glucosidase can be a potential strategy to improve the TB therapeutic outcomes. [Display omitted] • The extracellular polymeric substance in M.smegmatis biofilms are rich in lipids and polysaccharides. • β-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit anti-biofilm activity against M.smegmatis biofilms. • Treatment with β-glucosidase, Phytase and ɑ-amylase decreases the biofilm biomass without affecting viability of the bacterium. • Phytase, ɑ-amylase and β-glucosidase immobilized Rifampicin loaded SFNs exhibits dual antibacterial and biofilm eradication activity against pre-formed M.smegmatis biofilms. • Phytase, ɑ-amylase and β-glucosidase immobilized SFNs can be a potential candidate for treating mycobacterial biofilm infections. [ABSTRACT FROM AUTHOR]

Abstract The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases. Graphical Abstract

Unlike superficial fungal infections of the skin and nails, which are the most common fungal diseases in humans, invasive fungal infections carry high morbidity and mortality, particularly those associated with biofilm formation on indwelling medical devices. Therapeutic management of these complex diseases is often complicated by the rise in resistance to the commonly used antifungal agents. Therefore, the availability of accurate susceptibility testing methods for determining antifungal resistance, as well as discovery of novel antifungal and antibiofilm agents, are key priorities in medical mycology research. To direct advancements in this field, here we present an overview of the methods currently available for determining (i) the susceptibility or resistance of fungal isolates or biofilms to antifungal or antibiofilm compounds and compound combinations; (ii) the in vivo efficacy of antifungal and antibiofilm compounds and compound combinations; and (iii) the in vitro and in vivo performance of anti-infective coatings and materials to prevent fungal biofilm-based infections.

Lactic acid bacteria (LAB) naturally inhabits the organisms of honeybees and can exhibit adhesive properties that protect these insects against various pathogenic microorganisms. Thus, cell surface (auto-aggregation, co-aggregation, hydrophobicity) and adhesive properties of LAB to two abiotic (polystyrene and glass) and four biotic (collagen, gelatin, mucus, and intestinal Caco-2 cells) surfaces were investigated. Additionally, anti-adhesion activity and the eradication of honeybee pathogen biofilms by LAB metabolites (culture supernatants) were determined. The highest hydrophobicity was demonstrated by Pediococcus pentosaceus 19/1 (63.16%) and auto-aggregation by Lactiplantibacillus plantarum 18/1 (71.91%). All LAB showed a broad spectrum of adhesion to the tested surfaces. The strongest adhesion was noted for glass. The ability to co-aggregate with pathogens was tested for the three most potently adherent LAB strains. All showed various levels of co-aggregation depending on the pathogen. The eradication of mature pathogen biofilms by LAB metabolites appeared to be weaker than their anti-adhesive properties against pathogens. The most potent anti-adhesion activity was observed for L. plantarum 18/1 (98.80%) against Paenibacillus apiarius DSM 5582, while the strongest biofilm eradication was demonstrated by the same LAB strain against Melissococcus plutonius DSM 29964 (19.87%). The adhesive and anti-adhesive activity demonstrated by LAB can contribute to increasing the viability of honeybee colonies and improving the conditions in apiaries. [ABSTRACT FROM AUTHOR]

In this study, novel multilayered magnetic nanoparticles (ML-MNPs) loaded with DNase and/or vancomycin (Vanc) were fabricated for eliminating multispecies biofilms. Iron-oxide MNPs (IO-core) (500–800 nm) were synthesized via co-precipitation; further, the IO-core was coated with heavy-metal-based layers (Ag and MoS 2 NPs) using solvent evaporation. DNase and Vanc were loaded onto the outermost layer of the ML-MNP formed by nanoporous MoS 2 NPs through physical deposition and adsorption. The biofilms of S. mutans or E. faecalis (or both) were formed in a brain-heart-infusion broth (BHI) for 3 days, followed by treatment with ML-MNPs for 24 h. The results revealed that coatings of Ag (200 nm) and ultrasmall MoS 2 (20 nm) were assembled as outer layers of ML-MNPs successfully, and they formed Ag-Fe 3 O 4 @MoS 2 MNPs (3–5 μm). The DNase-Vanc-loaded MNPs caused nanochannels digging and resulted in the enhanced penetration of MNPs towards the bottom layers of biofilm, which resulted in a decrease in the thickness of the 72-h biofilm from 48 to 58 μm to 0–4 μm. The sustained release of Vanc caused a synergistic bacterial killing up to 96%–100%. The heavy-metal-based layers of MNPs act as nanozymes to interfere with bacterial metabolism and proliferation, which adversely affects biofilm integrity. Further, loading DNase/Vanc onto the nanoporous-MoS 2 -layer of ML-MNPs promoted nanochannel creation through the biofilm. Therefore, DNase-and Vanc-loaded ML-MNPs exhibited potent effects on biofilm disruption and bacterial killing. [Display omitted] • The infectious biofilm protects underlying colonies of bacteria. • Silver/iron/MoS 2 MNPspossess nanozyme activity and may co-deliver DNase/Vanc. • MNPs homogenously traversed the biofilm by digging the artificial nanochannels. • Thus, the co-delivery of DNase/Vanc@MNPs eradicated up to 70% of the biofilm thickness. • The sustained-release/prolonged-action of DNase/Vanc achieved 96%–100% loss of bacterial viability. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to develop a high‐throughput robotic microtiter plate‐based screening assay for Candida albicans, optimizing growth conditions to replicate the filamentous biofilm growth found in vivo, and subsequently, to demonstrate the assay by evaluating the effect of nutritional drinks alone and in combination with the antifungal amphotericin B (AmB). Methods and Results: Candida albicans cultured in a defined growth medium showed filamentous growth in microcolonies, mimicking the morphology of oral mucosal disease (oral candidiasis). Addition of nutrient drinks containing fruit juices, fish oil and whey protein to the medium resulted in changed morphology and promoted growth as free yeast cells and with weak biofilm structures. Minimum inhibitory concentration of AmB on the biofilms was 0.25 μg ml−1, and this was eightfold reduced (0.0038 μg ml−1) in the presence of the nutritional drinks. Conclusions: The established assay demonstrated applicability for screening of antifungal and anti‐biofilm effects of bioactive substances on C. albicans biofilm with clinically relevant morphology. Significance and Impact of the Study: Candida albicans is the causative agent of the majority of fungal infections globally. The filamentous morphology of C. albicans and the ability to form biofilm are traits known to increase virulence and resistance towards antifungals. This study describes the development of a plate‐based in vitro screening method mimicking the filamentous morphology of C. albicans found in vivo. The assay established can thus facilitate efficient antifungal drug discovery and development. [ABSTRACT FROM AUTHOR]

The presence of biofilm within a chronic wound may delay the healing process. Thus, control of biofilm formation and providing bactericidal effect are crucial factors for wound healing management. Alginate-based nanocomposite hydrogels have been suggested as dressing materials for wound treatment, which are employed as a biocompatible matrix. Therefore, in this study, we aimed to develop a biocompatible antimicrobial wound dressing containing AgNPs and demonstrate its efficacy against polymicrobial wound biofilms by using a biofilm flow device to simulate a chronic infected, exuding wound and specific wound environment. The results from agar well diffusion, the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays showed that TA-AgNPs exhibited antibacterial activity against wound pathogens. Additionally, the Minimum Biofilm Eradication Concentration assay (MBEC) demonstrated it could impair biofilm formation. Importantly, our TA-AgNPs/Alginate hydrogel clearly showed antibacterial activities against Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa. Furthermore, we used the biofilm flow device to test the topical antimicrobial hydrogel against a three-species biofilm. We found that TA-AgNPs/Alginate hydrogel significantly showed a 3–4 log reduction in bacterial numbers when applied with multiple doses at 24 h intervals, and was especially effective against the chronic wound pathogen P. aeruginosa. This work highlighted that the TA-AgNPs/Alginate hydrogel is a promising material for treating complex wound biofilms. [ABSTRACT FROM AUTHOR]

Developing efficient and safe approach to counteract the bacterial infections has become an urgent clinical challenge. In this work, we report folic acid derived carbon dots (FA-CDs) prepared by a one-step pyrolysis method. The FA-CDs can respond to the environmental stimuli of bacterial infections and acquire antimicrobial capacity "on demand" as a simple and effective antimicrobial nanosystem. The assays on antibacterial properties and mechanism show that FA-CDs are able to induce the gradual increase of intracellular reactive oxygen species (ROS) levels in bacteria under the simulated acidic environment and display pH-responsive biocidal activity. In a neutral condition, FA-CDs have no antibacterial activity, which will be conducive to mitigating the rise of bacterial drug resistance. The responsive antibacterial behavior can be attributed to that FA-CDs exhibit distinctive oxidase-like and peroxidase-like activity under acidic stimuli and inhibit the superoxide dismutase activity in bacteria cells, causing the accumulation of intracellular ROS. Meanwhile, FA-CDs can selectively kill Gram-positive bacterium S. aureus and remove mature biofilms. Besides, the in vitro and in vivo experiments demonstrate that FA-CDs possess excellent biocompatibility, and show remarkable therapeutic effect on the S. aureus -infected back wound models of mouse, which are crucial for clinical applications. Thus, this study highlights the potential application of FA-CDs as an ultra-succinct smart antimicrobial nanosystem for coping with infections caused by S. au reus in the clinical setting, and will bring about a new perspective on developing antimicrobial CDs. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetic wounds remain a critical clinical challenge due to their harsh microenvironment, which impairs cellular function, hinders re-epithelialization and tissue remodeling, and slows healing. Injectable nanocomposite hydrogel dressings offer a promising strategy for diabetic wound repair. In this study, we developed an injectable nanocomposite hydrogel dressing (HDL@W379) using LAP@W379 nanoparticles and an injectable hyaluronic acid-based hydrogel (HA-ADH-ODEX). This dressing provided a sustained, pH-responsive release of W379 antimicrobial peptides, effectively regulating the wound microenvironment to enhance healing. The HDL@W379 hydrogel featured multifunctional properties, including mechanical stability, injectability, self-healing, biocompatibility, and tissue adhesion. In vitro , the HDL@W379 hydrogel achieved synergistic biofilm elimination and subsequent activation of basal cell migration and endothelial cell tube formation. Pathway analysis indicated that the HDL@W379 hydrogel enhances basal cell migration through MEK/ERK pathway activation. In methicillin-resistant Staphylococcus aureus ( MRSA )-infected diabetic wounds, the HDL@W379 hydrogel accelerated wound healing by inhibiting bacterial proliferation and promoting re-epithelialization, regenerating the granulation tissue, enhancing collagen deposition, and facilitating angiogenesis. Overall, this strategy of biofilm elimination and basal cell activation to continuously regulate the diabetic wound microenvironment offers an innovative approach to treating chronic wounds.

Biofilms, which are resistant to conventional antimicrobial treatments, pose significant challenges in medical and industrial environments. This study introduces manganese complex-gold nanoparticles (Mn-DPA-AuNPs) as a hybrid strategy for biofilm inhibition and eradication. Upon exposure to green light, these nanoparticles significantly enhance the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide. This activity substantially reduces the regrowth potential of the surviving bacteria within the biofilm, with marked efficacy noted in Pseudomonas aeruginosa PAO1. This study highlights the potential of integrating manganese complexes with gold nanoparticles to develop advanced antimicrobial agents against resistant biofilms, offering a promising approach to enhance microbial control in diverse settings., (© 2024 Wiley-VCH GmbH.)

Candida auris is a rapidly spreading virulent pathogen frequently resistant to multiple antifungal drugs that can form biofilms and infect wounds. Hence, there is a need for C. auris wound treatments not posing risks for developing antifungal resistance. We tested the ability of a polygalacturonic and caprylic acid ointment (PG+CAP) to rapidly eradicate C. auris biofilms within 2-hour exposures in an in vitro model. Medical-grade honey (MediHoney) wound ointment was used as a comparator. Nine different C. auris strains were tested. PG+CAP eradicated biofilms of 8 of the 9 tested strains and produced a > 5-log 10 reduction of the ninth. MediHoney produced reductions ranging from 2 to 4 log 10 without fully eradicating any strains. The differences between PG+CAP and MediHoney were statistically significant (p < 0.05). These results suggest that PG+CAP is a promising antimicrobial ointment warranting further in vivo study in wounds which may be colonized by C. auris biofilms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of wound infections, often progressing into serious invasive bloodstream infections. MRSA disproportionately affects Indigenous peoples in Canada with higher rates of skin and wound infections, an example of persistent gaps in health outcomes between Indigenous and non-Indigenous peoples precipitated by the legacy of colonialism. Conversely, Indigenous peoples have long used natural remedies for infections and other diseases; however, their knowledge was rarely considered for modern medicine. The stagnant antibiotic discovery pipeline and alarming rise of resistance to current antibiotics prompted us to turn to Indigenous medicine as an untapped source of antimicrobials. As such, we collected and prepared 85 extracts of medicinal plants of value to Indigenous peoples spanning the Canadian Prairies. We explored the antimicrobial potential of these extracts against MRSA under wound infection-mimetic conditions compared with culture media typically used to study bacterial antibiotic responses and biofilms but not adequately representative of infection sites. We identified extracts with MRSA growth inhibitory [ e.g. , bergamot, dock, gaillardia, and dandelion extracts] and biofilm prevention and eradication [ e.g. , gumweed extracts] activities. Extracts, including those of chokecherry, hoary puccoon, and Northern bedstraw, were only active under wound infection-mimetic conditions, highlighting the benefit of antibiotic discovery under host-relevant conditions. Testing growth inhibitory extracts against an S. aureus cross-resistance platform suggested that they act through mechanisms likely distinct from known antibiotic classes. Together, through an interdisciplinary partnership leveraging Western approaches and traditional Indigenous knowledge, we identified plant extracts with promising antimicrobial potential for drug-resistant MRSA wound infections.IMPORTANCEWe explored the antimicrobial potential of traditional Indigenous remedies against MRSA under wound infection-mimetic conditions. We chose to tackle MRSA wound infections because they constitute an Indigenous health priority, ensuring mutual benefits and reciprocity, which are important principles in partnerships between Indigenous and non-Indigenous researchers. Our partnerships strive to serve as steps towards reconciliation with Indigenous peoples in Canada and a roadmap inspiring similar interdisciplinary collaborations to tackle other healthcare priorities. We identified extracts with promising antibacterial growth inhibitory, biofilm prevention, and eradication activities against MRSA. The antimicrobial potential of some extracts was only observed under wound infection-mimetic conditions, a proof-of-concept that screening under infection-mimetic conditions reveals novel activity undetected under standard conditions. The natural product antimicrobial extracts discovered herein warrant further investigation into their mode of action and chemical composition; they may address the dire need for new antimicrobial and anti-biofilm activity to counter the AMR crisis.

Biofilm-associated wound infection is principally perceived as the bacterial defense mechanism that hinders antibiotic penetration, causes toxin impairment, and suppresses the immunological responses of the host immune system. Several antibiofilm agents have been developed, but the least of these agents can simultaneously cornerstone on the biofilm-associated immunosuppression and bacterial toxin-induced cellular dysfunction. Inspired by the fusogenic property of nanodroplets and immunomodulatory functions of metal nanoparticles, biofilm targeted anti-virulent immunomodulatory cationic nanoparticle shelled nanodroplets (C-AgND) is fabricated to completely disintegrate and eradicate the Staphylococcus aureus (S. aureus) biofilm. The specific binding of C-AgND neutralizes the negatively charged EPS layer, causing their destabilization followed by penetration of the nanoformulation into the biofilm matrix, killing the persister cells. Consequently, C-AgND eliminates the virulence property of the S. aureus biofilm through α-hemolysin neutralization. C-AgND promotes a strong immunomodulatory effect by polarizing macrophages into their M1 phenotype to induce phagocytosis of the disintegrated biofilm-released residual cells, rejuvenating the host's innate immune responses for the complete eradication of the biofilm. Moreover, the ex vivo skin wound infection model illustrates an excellent biofilm eradication efficacy of C-AgND in comparison to the commercial ones, rendering them to be a promising replacement of existing antibiofilm agents in clinical application., (© 2024 Wiley‐VCH GmbH.)

The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties.