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Infectious diseases represent a significant global health challenge, with bacteria, fungi, viruses, and parasitic protozoa being significant causative agents. The shared symptoms among diseases and the emergence of new pathogen variations make diagnosis and treatment complex. Conventional diagnostic methods are laborious and intricate, underscoring the need for rapid, accurate techniques. Aptamer-based technologies offer a promising solution, as they are cost-effective, sensitive, specific, and convenient for molecular disease diagnosis. Aptamers, which are single-stranded RNA or DNA sequences, serve as nucleotide equivalents of monoclonal antibodies, displaying high specificity and affinity for target molecules. They are structurally robust, allowing for long-term storage without substantial activity loss. Aptamers find applications in diverse fields such as drug screening, material science, and environmental monitoring. In biomedicine, they are extensively studied for biomarker detection, diagnostics, imaging, and targeted therapy. This comprehensive review focuses on the utility of aptamers in managing infectious diseases, particularly in the realms of diagnostics and therapeutics.

Urinary tract infections (UTIs) are the second most common infectious disease, predominantly impacting women with 150 million individuals affected globally. It increases the socio-economic burden of society and is mainly caused by Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter spp., and Staphylococcus spp. The severity of the infection correlates with the host factors varying from acute to chronic infections. Even with a high incidence rate, the diagnosis is mainly based on the symptoms, dipstick analysis, and culture analysis, which are time-consuming, labour-intensive, and lacking sensitivity and specificity. During this period, medical professionals prescribe empirical antibiotics, which may increase the antimicrobial resistance rate. Timely and precise UTI diagnosis is essential for addressing antibiotic resistance and improving overall quality of life. In response to these challenges, new techniques are emerging. The review provides a comprehensive overview of the global burden of UTIs, associated risk factors, implicated organisms, traditional and innovative diagnostic methods, and approaches to UTI treatment and prevention.

Abstract Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis. Resistance in Candida albicans is initiated by morphological changes from yeast to hyphal form. This transition triggers a series of events such as cell wall elongation, increased adhesion, invasion of host tissues, pathogenicity, biofilm formation, and the initiation of an immune response. The cell wall is a critical interface for interactions with host cells, primarily through various cell wall proteins, particularly mannoproteins. Thus, cell wall proteins and enzymes are considered potential antifungal targets. In this regard, we explored α-glucosidase as our potential target which plays a crucial role in processing mannoproteins. Previous studies have shown that inhibition of α-glucosidase leads to defects in cell wall integrity, reduced adhesion, diminished secretion of hydrolytic enzymes, alterations in immune recognition, and reduced pathogenicity. Since α-glucosidase, primarily converts carbohydrates, our study focuses on FDA-approved carbohydrate mimic drugs (Glycomimetics) with well-documented applications in various biological contexts. Through virtual screening of 114 FDA-approved carbohydrate-based drugs, a pseudo-sugar Acarbose, emerged as a top hit. Acarbose is known for its pharmacological potential in managing type 2 diabetes mellitus by targeting α-glucosidase. Our preliminary investigations indicate that Acarbose effectively inhibits C. albicans biofilm formation, reduces virulence, impairs morphological switching, and hinders the adhesion and invasion of host cells, all at very low concentrations in the nanomolar range. Furthermore, transcriptomic analysis reveals the mechanism of action of Acarbose, highlighting its role in targeting α-glucosidase.

Abstract According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5–100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1IIIB, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal–mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.

Abstract The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation—solvent evaporation method, which showed optimum average particle size of 230–280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.

Staphylococcus aureus leads to diverse infections, and their treatment relies on the use of antibiotics. Nevertheless, the rise of antibiotic resistance poses an escalating challenge and various mechanisms contribute to antibiotic resistance, including modifications to drug targets, enzymatic deactivation of drugs, and increased efflux of antibiotics. Hence, the quest for innovative antimicrobial solutions has intensified in the face of escalating antibiotic resistance and the looming threat of superbugs. The NorA protein of S. aureus, classified as an efflux pump within the major facilitator superfamily, when overexpressed, extrudes various substances, including fluoroquinolones (such as ciprofloxacin) and quaternary ammonium. Addressing this, the unexplored realm of inorganic and organometallic compounds in medicinal chemistry holds promise. Notably, the study focused on investigating two different series of palladium-based metal complexes consisting of QSL_PA and QSL_PB ligands to identify a potent NorA efflux pump inhibitor that can restore the susceptibility to fluoroquinolone antibiotics. QSL_Pd5A was identified as a potent efflux pump inhibitor from the real-time efflux assay. QSL_Pd5A also resensitized SA1199B to ciprofloxacin at a low concentration of 0.125 µg/mL without elucidating cytotoxicity on the NRK-62E cell line. The in vitro findings were substantiated by docking results, indicating favorable interactions between QSL_Pd5A and the NorA efflux pump.

Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by the complex interactions within these communities for generations. The presence of specific microorganisms warrants a chronic infection and impacts crucial factors such as virulence and antibiotic susceptibility. Game theory is valuable for scenarios involving multiple decision-makers, but its relevance to polymicrobial infections is limited. Eco-evolutionary dynamics introduce causation for multiple proteomic interactions like metabolic syntropy and niche segregation. The review culminates both these giants to form evolutionary dynamics (ED). There is a significant amount of literature on inter-bacterial interactions that remain unsynchronised. Such raw data can only be moulded by analysing the ED involved. The review culminates the inter-bacterial interactions in multiple clinically relevant polymicrobial infections like chronic wounds, CAUTI, otitis media and dental carries. The data is further moulded with ED to analyse the niche colonisation of two notoriously competitive bacteria: S.aureus and P.aeruginosa. The review attempts to develop a future trajectory for polymicrobial research by following recent innovative strategies incorporating ED to curb polymicrobial infections.

Candida albicans-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence, development of resistance, and poor penetration into the biofilm matrix. Various predisposition factors are molecular drivers that lead to the dysbiosis of normal microflora of the vagina, upregulation of central metabolic pathways, morphogenesis, hyphal extension, adhesion, invasion, and biofilm formation leading to chronic infection and recurrence. Hence, it is crucial to understand the molecular mechanism behind the virulence pathways driven by those drivers to decode the drug targets. Finding innovative solutions targeting fungal virulence/biofilm may potentiate the antifungals at low concentrations without affecting the recurrence of resistance. With this background, the present review details the critical molecular drivers and associated network of virulence pathways, possible drug targets, target-specific inhibitors, and probable mode of drug delivery to cross the preclinical phase by appropriate in vivo models.

Nanocomposites, formed by combining a matrix (commonly polymer or ceramic) with nanofillers (nano-sized inclusions like nanoparticles or nanofibers), possess distinct attributes attributed to their composition. Their unique physicochemical properties and interaction capabilities with microbial cells position them as a promising avenue for infectious disease treatment. The escalating prevalence of multi-drug resistant bacteria intensifies the need for alternative solutions. Traditional approaches involve antimicrobial agents like antibiotics, antivirals, and antifungals, targeting specific microbial aspects. This review presents a comprehensive overview of diverse nanocomposite types and highlights the potential of tailored matrix and antibacterial agent selection within nanocomposites to enhance treatment efficacy and decrease antibiotic resistance risks. Challenges such as toxicity, safety, and scalability in clinical applications are also acknowledged. Ultimately, the convergence of nanotechnology and infectious disease research offers the prospect of enhanced therapeutic strategies, envisioning a future wherein advanced materials revolutionize the landscape of medical treatment.

Abstract Vibrio cholerae causes cholera, an acute diarrhoeal disease. The virulence in V. cholerae is regulated by the quorum-sensing mechanism and response regulator LuxO positively regulates the expression of virulence determinants adhesion, biofilm formation, and cholera toxin production. Previous in-silico studies revealed that 2-methoxy-4-vinylphenol could bind to the ATP binding site of LuxO and the complex was compact and stable in pHs like intestinal pHs. Here, we have explored the polymeric nano-formulation of 2-methoxy-4-vinylphenol using cellulose acetate phthalate for controlled drug release and their effectiveness in attenuating the expression of V. cholerae virulence. Physico-chemical characterization of the formulation showed particles with a mean size of 91.8 ± 14 nm diameter and surface charge of − 14.7 ± 0.07 mV. The uniform round polymeric nanoparticles formed displayed about 51% burst release of the drug at pH 7 by 3rd h, followed by a controlled linear release in alkaline pH. The polymeric nanoparticles demonstrated a tenfold increase in intestinal membrane permeability ex-vivo. At lower concentrations, the 2-methoxy-4-vinylphenol polymeric nanoparticles were non-cytotoxic to Int 407 cells. In-vitro analysis at pH 6, pH 7, pH 8, and pH 9 revealed that cellulose acetate phthalate—2-methoxy-4-vinylphenol nanoparticles were non-bactericidal at concentrations up to 500 μg/mL. At 31.25 μg/mL, the nanoparticles inhibited about 50% of the biofilm formation of V. cholerae MTCC 3905 and HYR14 strains. At this concentration, the adherence of V. cholerae MTCC 3905 and HYR14 to Int 407 cell lines were also significantly affected. Gene expression analysis revealed that the expression of tcp, qrr, and ct at pH 6, 7, 8, and 9 has reduced. The CAP-2M4VP nanoparticles have demonstrated the potential to effectively reduce the virulence of V. cholerae in-vitro.

Healthcare settings have dramatically advanced the latest medical devices, such as urinary catheters (UC) for infection, prevention, and control (IPC). The continuous or intermittent flow of a warm and conducive (urine) medium in the medical device, the urinary catheter, promotes the formation of biofilms and encrustations, thereby leading to the incidence of CAUTI. Additionally, the absence of an innate immune host response in and around the lumen of the catheter reduces microbial phagocytosis and drug action. Hence, the review comprehensively overviews the challenges posed by CAUTI and associated risks in patients’ morbidity and mortality. Also, detailed, up-to-date information on the various strategies that blended/tailored the surface properties of UC to have anti-fouling, biocidal, and anti-adhesive properties to provide an outlook on how they can be better managed with futuristic solutions.

The human–bacterial association is long-known and well-established in terms of both augmentations of human health and attenuation. However, the growing incidents of nosocomial infections caused by the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.) call for a much deeper understanding of these organisms. Adopting a holistic approach that includes the science of infection and the recent advancements in preventing and treating infections is imperative in designing novel intervention strategies against ESKAPE pathogens. In this regard, this review captures the ingenious strategies commissioned by these master players, which are teamed up against the defenses of the human team, that are equally, if not more, versatile and potent through an analogy. We have taken a basketball match as our analogy, dividing the human and bacterial species into two teams playing with the ball of health. Through this analogy, we make the concept of infectious biology more accessible.

Advancements in biomedical devices are ingenious and indispensable in health care to save millions of lives. However, microbial contamination paves the way for biofilm colonisation on medical devices leading to device-associated infections with high morbidity and mortality. The biofilms elude antibiotics facilitating antimicrobial resistance (AMR) and the persistence of infections. This review explores nature-inspired concepts and multi-functional approaches for tuning in next-generation devices with antibacterial surfaces to mitigate resistant bacterial infections. Direct implementation of natural inspirations, like nanostructures on insect wings, shark skin, and lotus leaves, has proved promising in developing antibacterial, antiadhesive, and self-cleaning surfaces, including impressive SLIPS with broad-spectrum antibacterial properties. Effective antimicrobial touch surfaces, photocatalytic coatings on medical devices, and conventional self-polishing coatings are also reviewed to develop multi-functional antibacterial surfaces to mitigate healthcare-associated infections (HAIs).

Currently available diagnostic procedures for infections are laborious and time-consuming, resulting in a substantial financial burden by increasing morbidity, increased costs of hospitalization, and mortality. Therefore, innovative approaches to design diagnostic biomarkers are imperative to assist in the rapid and sensitive diagnosis of microbial infections. Acyl homoserine lactones (AHLs) are ubiquitous bacterial signaling molecules that are found to be significantly upregulated in infected sites. In this pioneering work, we have developed a simple photoluminescence-based assay using cysteamine-capped titanium oxide (TiO2) nanoparticles for AHL detection. The PL intensity variation of the oxygen defect state of TiO2 was used for the biosensing measurements. The bioassays were validated using two well-studied AHL molecules (C4-HSL and 3-oxo-C12 HSL) of an important human pathogen, Pseudomonas aeruginosa. The developed system has a maximum relative response of 98%. Furthermore, the efficacy of the system in simulated host urine using an artificial urine medium showed a linear detection range of 10–160 nM. Also, we confirmed the relative response and specificity of the system in detecting AHLs produced by P. aeruginosa in a temporal manner.

Efflux pumps are one of the predominant microbial resistant mechanisms leading to the development of multidrug resistance. In Staphylococcus aureus, overexpression of NorA protein enables the efflux of antibiotics belonging to the class of fluoroquinolones and, thus, makes S. aureus resistant. Hence, NorA efflux pumps are being extensively exploited as the potential drug target to evade bacterial resistance and resensitize bacteria to the existing antibiotics. Although several molecules are reported to inhibit NorA efflux pump effectively, boronic acid derivatives were shown to have promising NorA efflux pump inhibition. In this regard, the current study exploits 6-(3-phenylpropoxy)pyridine-3-boronic acid to further improve the activity and reduce cytotoxicity using the bioisostere approach, a classical medicinal chemistry concept. Using the SWISS-Bioisostere online tool, from the parent compound, 42 compounds were obtained upon the replacement of the boronic acid. The 42 compounds were docked with modeled NorA protein, and key molecular interactions of the prominent compounds were assessed. The top hit compounds were further analyzed for their drug-like properties using ADMET studies. The identified potent lead, 5-nitro-2-(3-phenylpropoxy)pyridine (5-NPPP), was synthesized, and in vitro efficacy studies have been proven to show enhanced efflux inhibition, thus acting as a potent antibiotic breaker to resensitize S. aureus without elucidating any cytotoxic effect to the host Hep-G2 cell lines.

Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70–75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.

Uropathogenic Escherichia coli (UPEC) accounts for the majority of complicated and uncomplicated urinary tract infections. The use of phytomolecules in the treatment of UTI is fast gaining attention. The current report identifies a multidrug-resistant strain (QSLUPEC7), which is a strong biofilm producer, among the considered clinical isolates. The antimicrobial and antibiofilm activity was evaluated for the phytomolecule, Type A procyanidin (TAP) from Cinnamomum zeylanicum against QSLUPEC7. TAP treatment did not affect the growth of the MDR strain but affected the biofilm formation (~70% inhibition). The confocal microscopic examination reveals the biofilm inhibition and the live cells in the biofilm corroborates the antimicrobial results. Further, the synergy studies of TAP and nitrofurantoin (NIT) were carried out at different pH. TAP acts synergistically with nitrofurantoin at different pH considered. A closer look in the results reveals that at pH 5.8, maximum growth inhibition is recorded. The gene expression analysis shows that TAP alone and in combination with NIT downregulates the major fimbriae adhesins of UPEC. The results conclude that the TAP has an antibiofilm activity against the multidrug-resistant strain of UPEC, without affecting the growth. Also, TAP reciprocally cooperates with nitrofurantoin at different pH by downregulating the adhesins of UPEC.

Vibrio cholerae, the etiological agent of cholera, employs quorum sensing (QS) pathways to control the expression of virulence factors, including the production of cholera toxin and biofilm formation. Acquired antibiotic resistance in V. cholerae draws attention to the development of novel therapeutics that counteract virulence, rather than the viability of the pathogen. In this context, we explored the anti-infective potential of rare marine Actinobacteria (RMA) from a mangrove ecosystem. Here, we report the effects of Micromonospora sp. RMA46 against V. cholerae in vitro. The RMA46 organic extract was non-bactericidal to V. cholerae cells and non-cytotoxic to macrophage RAW264.7 cell lines. RMA46 inhibited the formation of V. cholerae biofilms and downregulated the QS global switches LuxO and HapR, as well as other virulence genes including ct, tcp, and hapA. In silico molecular docking simulation of RMA46 ethyl acetate extract with LuxO and HapR revealed that 2-methoxy-4-vinylphenol and hexahydro-3-(phenylmethyl)-pyrrolo[1,2-a]pyrazine-1,4-dione could interact with the active sites of LuxO and HapR and potentially inhibit them. This study highlights Micromonospora sp. RMA46 as a potential source of anti-infectives against V. cholerae.

The rapid dissemination of antimicrobial resistance amongst microorganisms and their deleterious effect on public health has propelled the exploration of alternative interventions that target microbial virulence rather than viability. In several microorganisms, the expression of virulence factors is controlled by quorum sensing systems. A comprehensive understanding into microbial quorum sensing systems, virulence strategies and pathogenesis has exposed potential targets whose attenuation may alleviate infectious diseases. Such virulence attenuating natural products sourced from the different phyla of bacteria from diverse ecosystems have been identified. In this review, we discuss chemical entities derived from the phylum Actinobacteria that have demonstrated the potential to inhibit microbial biofilms, enzymes, and other virulence factors both in vivo and in vitro. We also review Actinobacteria-derived compounds that can degrade quorum sensing signal molecules, and the genes encoding such molecules. As many Actinobacteria-derived compounds have been translated into pharmaceutically important agents including antibiotics, the identification of virulence attenuating compounds from this phylum exemplifies their significance as a prospective source for anti-virulent drugs.

Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need to identify compounds that curb the virulence of pathobionts without microbial killing. Through this study, we have demonstrated for the first time that 5,6,7-trihydroxyflavone (Baicalein) significantly downregulates crucial caries-related virulence phenotypes in Streptococcus mutans. Baicalein significantly inhibited biofilm formation by Streptococcus mutans UA159 (MBIC50 = 200 μM), without significant growth inhibition. Notably, these concentrations of baicalein did not affect the commensal S. gordonii. Strikingly, baicalein significantly reduced cell surface hydrophobicity, autoaggregation and acid production by S. mutans. Mechanistic studies (qRT-PCR) showed downregulation of various genes regulating biofilm formation, surface attachment, quorum sensing, acid production and competence. Finally, we demonstrate the potential translational value of baicalein by reporting synergistic interaction with fluoride against S. mutans biofilms.

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.

An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.