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Background Methods Results Conclusion Routine prescription of antibiotics to treat chronic rhinosinusitis (CRS) exacerbations may contribute to the propagation of antibiotic resistance. Hops bitter β‐acids lupulone and colupulone possess potent antibacterial activities and, as T2R1, T2R14, and/or T2R40 agonists, may improve the impaired mucociliary clearance described in CRS patients. We investigated these molecules as alternative treatments to antibiotics in CRS management based on their antibacterial and T2Rs agonists properties.Human nasal primary cells (HNECs) and RPMI2650 cells cultures were used as study models. T2Rs expression in cell culture models and human nasal tissue was assessed using immunofluorescence, quantitative PCR, and Western blot. We performed calcium imaging and cilia beat frequency experiments to investigate T2Rs activation in study models in response to lupulone and colupulone stimulations. Finally, we studied hops β‐acids cytotoxicity on cells using CellEvent, crystal violet, lactate dehydrogenase assays, immunofluorescence, and transepithelial electrical resistance assays.We confirmed lupulone and colupulone potent antibacterial effect on CRS‐relevant methicillin‐resistant Staphylococcus aureus but found minimal impact on P. aeruginosa. We also report T2R1, T2R14 and T2R40 expression in HNECs and RPMI2650 cell cultures. Lupulone and colupulone induced an increase in cytosolic calcium that appeared dependent on T2Rs signaling. This response was accompanied by mitochondrial membrane depolarization, cellular energy stress, decreased cell proliferation, ciliostasis, and HNECs remodeling after a single exposure to lupulone at micromolar concentrations.Our data suggest that hops β‐acids may not be beneficial as treatments in CRS patients and instead contribute to the disease by impairing cell health and further deteriorating the MCC. [ABSTRACT FROM AUTHOR]

In this investigation, we assessed the antibacterial properties of menthol using Escherichia coli strains, including a tetracycline-resistant (BN407) and a non-resistant reference (K12) strains. The disc-diffusion assay indicated remarkable antibacterial activity of menthol, warranting further exploration. The minimum inhibitory concentration (MIC) for menthol was determined to be 500 µg/ml for both strains. Despite identical MIC values, menthol exhibited different effects on the colony-forming units (CFUs) of the strains, reducing CFUs by 55% in E. coli K12 and 40% in E. coli BN407.Growth kinetics studies revealed that menthol extended the Lag phase by 50% and decreased the specific growth rate and mean generation time by nearly 50% for both strains. These findings illustrate menthol's significant impact on bacterial replication and adaptation processes. Additionally, menthol disrupted membrane-associated properties, as evidenced by reduced H+-flux through bacterial membranes, affecting both N,N-Dicyclohexylcarbodiimide (DCCD)-sensitive and non-sensitive proton flux rates. This indicates that menthol compromises the proton motive force critical for ATP synthesis and nutrient transport.In summary, menthol demonstrates potent antibacterial activity, influencing bacterial growth and survival. This activity is supposed to be due to the influence on membrane functionality. These effects are consistent across both tetracycline-resistant and non-resistant E. coli strains.

Background: Macrolides inhibit the growth of bacterial cells by preventing the elongation of polypeptides during protein biosynthesis and include natural, synthetic, and semi-synthetic products. Elongation prevention occurs by blocking the passage of the polypeptide chain as the macrolides bind at the nascent peptide exit tunnel. Objective: Recent data of ribosome profiling via ribo-seq further proves that, other than blocking the polypeptide chain, macrolides are also able to affect the synthesis of individual proteins. Thus, this shows that the mode of action of macrolides is more complex than we initially thought. Since the discovery of macrolides in the 1950s, they have been widely used in veterinary practice, agriculture, and medicine. Due to misuse and overuse of antibiotics, bacteria have acquired resistance against them. Hence, it is of utmost importance for us to fully understand the mode of action of macrolides as well as the mechanisms of resistance against macrolides in order to mitigate antibiotic-resistance issues. Results: Chemical modifications can be performed to improve macrolide potency if we have a better understanding of their mode of action. Furthermore, a complete and detailed understanding of the mode of action of macrolides has remained vague, as new findings have challenged theories that are already in existence—due to this obscurity, research into macrolide modes of action continues to this day. Conclusion: In this review, we present an overview of macrolide antibiotics, with an emphasis on the latest knowledge regarding the mode of action of macrolides as well as the mechanisms of resistance employed by bacteria against macrolides.

In this investigation, we assessed the antibacterial properties of menthol using Escherichia coli strains, including a tetracycline-resistant (BN407) and a non-resistant reference (K12) strains. The disc-diffusion assay indicated remarkable antibacterial activity of menthol, warranting further exploration. The minimum inhibitory concentration (MIC) for menthol was determined to be 500 µg/ml for both strains. Despite identical MIC values, menthol exhibited different effects on the colony-forming units (CFUs) of the strains, reducing CFUs by 55% in E. coli K12 and 40% in E. coli BN407. Growth kinetics studies revealed that menthol extended the Lag phase by 50% and decreased the specific growth rate and mean generation time by nearly 50% for both strains. These findings illustrate menthol's significant impact on bacterial replication and adaptation processes. Additionally, menthol disrupted membrane-associated properties, as evidenced by reduced H+-flux through bacterial membranes, affecting both N,N-Dicyclohexylcarbodiimide (DCCD)-sensitive and non-sensitive proton flux rates. This indicates that menthol compromises the proton motive force critical for ATP synthesis and nutrient transport. In summary, menthol demonstrates potent antibacterial activity, influencing bacterial growth and survival. This activity is supposed to be due to the influence on membrane functionality. These effects are consistent across both tetracycline-resistant and non-resistant E. coli strains. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant microbes have been closely associated with drug misuse and careless drug disposal, indicating a mutualistic relationship between certain environmental conditions and antibiotic resistance. This study investigates the effects of the sound on the growth and antibiotic susceptibility of ESBL-producing E. coli (ESBL-E. coli). We examined how various frequencies, intensities, and powers of sound exposure influenced E. coli development and antibiotic resistance. Our findings revealed that E. coli exposed to sound waves exhibited a more rapid specific growth rate and higher biomass compared to the control group. Specifically, the average length of E. coli cells increased by over 27.26%. The stimulation group experienced maximum biomass and specific growth rates approximately 1.7 and 2.5 times higher than the control group when exposed to an 8000 Hz, 80 dB sound wave. Before receiving sound treatment, ESBL-E. coli showed resistance to four antibiotics: amoxicillin/clavulanic acid, trimethoprim/sulfonamides, ciprofloxacin, and gentamicin. However, post-treatment susceptibility tests indicated that these antibiotics became effective. The study demonstrates that the moderate sound wave significantly impacts multidrug-resistant ESBL-E. coli. Attempts to enhance the sound effect using probiotic bacteria from kefir and kombucha showed no improvement. Notably, certain Moderate sound verses had a profound impact on E. coli, suggesting a unique approach to combating antibiotic resistance. Considering projections that effective antibiotics might be scarce between 2030 and 2050, this study offers a promising alternative. This groundbreaking research holds significant potential for application in Saudi Arabia and globally. We have secured a patent for this innovation from the United States of America, underscoring its importance and potential impact. [ABSTRACT FROM AUTHOR]

BackgroundThe growing number of antimicrobial-resistant bacteria in a range of environments poses a serious challenge to infectious disease prevention. Good water quality is critical to human health and has a direct impact on a country’s socio-economic growth. Therefore, assessing the bacteriological quality of drinking water provides benchmark data and provides insight into the development of further protection and treatment measures.MethodsA cross-sectional study was conducted from February 1, 2022, to September 31, 2023, in the diarrhea hotspot areas of North Shewa Zone (Minjar-Shenkora and Mojana-Wedera districts). Water samples were collected from drinking water sources (hand-pumps, boreholes, wells, spring water and ponds) to assess the quality following WHO guidelines. The collected water samples were processed for bacterial isolation, antimicrobial susceptibility testing, and detection of antimicrobial resistance genes. Data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS) version 25.ResultsA total of (49/138, 35.5%) bacteria were isolated from 138 drinking water samples, with a positive rate of (41/138, 29.7%). Among the isolates, (16/138, 11.6%) were Staphylococcus aureus while (33/138, 23.9%) were members of Enterobacteriaceae. Relatively high resistance rate among all isolates were observed for the most prescribed antibiotics in Ethiopia, including erythromycin, cotrimoxazole, doxycycline, ceftriaxone, gentamicin, and chloramphenicol. However, a low resistance was observed for early introduced antibiotics such as ciprofloxacin and recently introduced antibiotics such as cefotaxime, ceftazidime, imipenem, and meropenem. Among the 49 bacteria isolates, (32/49, 65.3%) were multidrug-resistant (MDR) pathogens while (12/49, 24.5%) were ESβL producers. Different ESβL genes were detected in most bacterial isolates. The predominant ESβL genes were blaCTX-M-gp8/25 (6/33, 18.2%), blaCTX-M-gp9 (5/33, 15.2%), and blaCTX-M-gp1 (5/33, 15.2%).ConclusionThe result of this study suggests that most water sources in the study area were contaminated by various bacterial species that are resistant to different antibiotics. Various ESβL resistance genes have also been detected. Therefore, regular sanitary inspection and bacteriological analysis should be mandatory to protect drinking water sources from contamination and the persistence of resistant bacteria.

Abstract Background The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. Methods From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. Results Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed

Enterococcus faecalis is among the most resistant bacteria found in infected root canals. The demand for cutting-edge disinfection methods has rekindled research on photoinactivation with visible light. This study investigated the bactericidal activity of femtosecond laser irradiation against vancomycin-resistant Enterococcus faecalis V583 (VRE). The effect of parameters such as wavelength and energy density on the viability and growth kinetics of VRE was studied to design an optimized laser-based antimicrobial photoinactivation approach without any prior addition of exogenous photosensitizers. The most effective wavelengths were 430 nm and 435 nm at a fluence of 1000 J/cm2, causing a nearly 2-log reduction (98.6% and 98.3% inhibition, respectively) in viable bacterial counts. The colony-forming units and growth rate of the laser-treated cultures were progressively decreased as energy density or light dose increased at 445 nm but reached a limit at 1250 J/cm2. At a higher fluence of 2000 J/cm2, the efficacy was reduced due to a photobleaching phenomenon. Our results highlight the importance of optimizing laser exposure parameters, such as wavelength and fluence, in bacterial photoinactivation experiments. To our knowledge, this is the first study to report an optimized wavelength for the inactivation of VRE using visible femtosecond laser light. [ABSTRACT FROM AUTHOR]

Background: Terminalia ferdinandiana Exell. fruit have been used by the First Australians as a nutritious food and as a medicine for thousands of years. The antibacterial properties of T. ferdinandiana fruit extracts are well reported. However, the therapeutic potential of plants growing in different locations and environmental conditions have not previously been compared. Aim: This study compares the antibacterial efficacy of fruit harvested from two distinct locations in Australia and correlates these activities with their physiochemical properties. Materials and Methods: The growth inhibitory activity of the T. ferdinandiana fruit extracts were evaluated using solid phase disc diffusion and liquid microdilution MIC assays. Artemia nauplii bioassays were used to screen and compare the extracts from both locations. Results: The T. ferdinandiana extracts prepared from fruits sourced from the two distinct regions of Australia inhibited the growth of the panel of bacteria screened, including a highly antibiotic MRSA strain. In general, the methanolic extracts were substantially better inhibitors of bacterial growth than the aqueous extracts, and extracts prepared using the Northern Territory (NT)-derived fruit were substantially more potent than the Western Australian (WA) fruit extracts. MICs substantially <1000 μg/mL were noted for the NT methanolic fruit extract against the reference S. aureus and MRSA bacterial strains respectively. The potency of this extract against the MRSA strain indicates that this extract may function via a distinct mechanism compared to the standard antibiotics tested. Interestingly, the greater antibacterial potency of the NT fruit extracts correlated to high ascorbic acid levels, indicating that the antibacterial mechanism may involve modulation of the redox state. All extracts were nontoxic in the Artemia nauplii toxicity assay, indicating their safety for therapeutic usage. Conclusion: The T. ferdinandiana fruit extracts prepared from both NT and WA each had noteworthy antibacterial activity, although greater activity was noted for the NT fruit extracts. This activity correlated with the antioxidant/ascorbic acid content of the extracts. All extracts were also nontoxic in the Artemia nauplii bioassay, although future studies using mammalian cell lines are required to confirm their safety for therapeutic use. [ABSTRACT FROM AUTHOR]

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography–mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study. [ABSTRACT FROM AUTHOR]

The accelerating rise of multi-drug resistance and resultant difficulties in the treatment of Pseudomonas aeruginosa infections are a significant cause of high morbidity and mortality in infected patients. Antimicrobial resistance resulting from biofilm contributes to a significant disease burden on public health and P.aeruginosa serves as a model for investigating biofilm development. Biofilm makes slime layer over various surfaces (epithelial layer, contact lenses, human teeth, urinary catheters, rocks) and when bacteria break away from the complex aggregation; are a source of serious healthcare-associated infections that are mainly systemic. Biofilm is a significant characteristic of about 99% of bacterial species and serves as a resistive and protective barrier from varied antibiotics. Biofilm communities form pillar-like structures. About 10% of Pseudomonas aeruginosa strains are resistant to antibiotics and account for 8% of urinary tract and pneumonia disorders. Resistance is achieved by numerous phenomena such as reducing outer membrane permeability, using an efflux pump, specialized enzymatical activity, biofilm formation, horizontal resistive-gene transfer, mutations, etc. In this study, we evaluated biofilm from every aspect 1) related to its formation, factors impacting its formation, and its role in antibiotic resistance especially in Pseudomonas. 2) Mechanisms through which P.aeroginosa illustrates intrinsic, adaptive as well as acquired resistance toward antibiotics. 3) Furthermore, the modern antibiotics to treat these resistive strains are also overviewed. Recently, novel therapeutic approaches have played a significant role in the treatment of resistive strains and may include non-antibiotic approaches or may be used with modern antibiotics to be more effective.

Antibiotic resistance in foodborne pathogens is an increasing threat to global human health. Among the most prevalent antibiotic-resistant bacteria are Salmonella enterica serovar Typhimurium, Campylobacter jejuni and E. coli 0157:H7. Control of these and other pathogens requires innovative approaches, i.e., discovering new molecules that will inactivate them, or render them less virulent without inducing resistance. Recently, several polyphenol molecules have been shown to possess such characteristics. Also, the use of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) approaches has recently been proposed for such purpose. This review summarizes the main findings regarding the application of both approaches to control the above-mentioned foodborne pathogens by relying on Quorum Sensing interference (Quorum Quenching) mechanisms and highlights the avenues needed for further research. [ABSTRACT FROM AUTHOR]

Vibrio bacterial species are dominant pathogens in mariculture animals. However, the extensive use of antibiotics and other chemicals has increased drug resistance in Vibrio bacteria. Despite rigorous investigative studies, the mechanism of drug resistance in Vibrio remains a mystery. In this study, we found that a gene encoding LamB-like outer membrane protein, named ArmPT, was upregulated in Va under antibiotic stress by RT-qPCR. We speculated that ArmPT might play a role in Va’s drug resistance. Subsequently, using ArmPT gene knockout and gene complementation experiments, we confirmed its role in resistance against a variety of antibiotics, particularly kanamycin (KA). Transcriptomic and proteomic analyses identified 188 and 83 differentially expressed genes in the mutant strain compared with the wild-type (WT) before and after KA stress, respectively. Bioinformatic analysis predicted that ArmPT might control cell membrane permeability by changing cadaverine biosynthesis, thereby influencing the cell entry of antibiotics in Va. The higher levels of intracellular reactive oxygen species and the infused content of KA showed that antibiotics are more likely to enter the Va mutant strain. These results uncover the drug resistance mechanism of Va that can also exist in other similar pathogenic bacteria.

BackgroundAmong multidrug-resistant (MDR) bacteria able to threaten human health, carbapenem-resistant Enterobacterales (CRE) have become a major public health threat globally. National and international guidelines point out the importance of active routine surveillance policies to prevent CRE transmission. Therefore, defining lines of intervention and strategies capable of containing and controlling the spread of CRE is considered determinant. CRE screening is one of the main actions to curb transmission and control outbreaks, outlining the presence and also the prevalence and types of carbapenemase enzymes circulating locally.ObjectiveThe purpose of this study was to outline the epidemiology of CRE colonization in Italy, detecting CRE-colonized patients at admission and during hospitalization, before and during the first year of COVID-19.Materials and methodsA total of 11,063 patients admitted to seven different hospitals (Bologna, Catania, Florence, Genoa, Naples, Palermo, and Turin) in Intensive Care Units (ICU) and other wards (non-ICU) located in the North, Center, and South of Italy were enrolled and screened for CRE carriage at admission (T0) and during the first 3 weeks of hospitalization (T1-T3). The study spanned two periods, before (September 2018-Septemeber 2019, I observational period) and during the COVID-19 pandemic (October 2019–September 2020, II observational period).ResultsOverall, the prevalence of CRE-colonized patients at admission in ICU or in other ward, ranged from 3.9 to 11.5%, while a percentage from 5.1 to 15.5% of patients acquired CRE during hospital stay. There were large differences between the I and II period of study according to the different geographical areas and enrolling centers. Overall, comparison of prevalence of CRE-positive patients showed a significant increased trend between I and II observational periods both in ICU and non-ICU wards, mostly in the Southern participating centers. KPC-producing Klebsiella pneumoniae was the most frequent CRE species-carbapenemase combination reported in this study. In particular, the presence of KPC-producing K. pneumoniae was reported in period I during hospitalization in all the CRE-positive patients enrolled in ICU in Turin (North Italy), while in period II at admission in all the CRE-positive patients enrolled in ICU in Catania and in 58.3% of non-ICU CRE-positive patients in Naples (both centers in South Italy).ConclusionThe prevalence of CRE in Italy highly increased during the COVID-19 pandemic, mostly in the Southern hospital centers. KPC-producing K. pneumoniae was the most frequent colonizing CRE species reported. The results of our study confirmed the crucial value of active surveillance as well as the importance of multicenter studies representing diverse geographical areas even in endemic countries. Differences in CRE colonization prevalence among centers suggest the need for diversified and center-specific interventions as well as for strengthening efforts in infection prevention and control practices and policies.

Abstract Background Hospitals with their high antimicrobial selection pressure represent the presumably most important reservoir of multidrug-resistant human pathogens. Antibiotics administered in the course of treatment are excreted and discharged into the wastewater system. Not only in patients, but also in the sewers, antimicrobial substances exert selection pressure on existing bacteria and promote the emergence and dissemination of multidrug-resistant clones. In previous studies, two main clusters were identified in all sections of the hospital wastewater network that was investigated, one K. pneumoniae ST147 cluster encoding NDM- and OXA-48 carbapenemases and one VIM-encoding P. aeruginosa ST823 cluster. In the current study, we investigated if NDM- and OXA-48-encoding K. pneumoniae and VIM-encoding P. aeruginosa isolates recovered between 2014 and 2021 from oncological patients belonged to those same clusters. Methods The 32 isolates were re-cultured, whole-genome sequenced, phenotypically tested for their antimicrobial susceptibility, and analyzed for clonality and resistance genes in silico. Results Among these strains, 25 belonged to the two clusters that had been predominant in the wastewater, while two others belonged to a sequence-type less prominently detected in the drains of the patient rooms. Conclusion Patients constantly exposed to antibiotics can, in interaction with their persistently antibiotic-exposed sanitary facilities, form a niche that might be supportive for the emergence, the development, the dissemination, and the maintenance of certain nosocomial pathogen populations in the hospital, due to antibiotic-induced selection pressure. Technical and infection control solutions might help preventing transmission of microorganisms from the wastewater system to the patient and vice versa, particularly concerning the shower and toilet drainage. However, a major driving force might also be antibiotic induced selection pressure and parallel antimicrobial stewardship efforts could be essential.

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography–mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study.

(1) Background: Antibiotic resistance is a serious health issue, and raising public awareness of it is crucial to combating it. This study aimed to assess the socio-demographic factors associated with knowledge of antibiotics and antibiotic resistance in Malaysia. (2) Methods: A cross-sectional study was carried out between April 2022 and March 2023. Malaysian adults aged ≥18 years old and able to understand English or Malay were recruited. During data collection, the WHO questionnaire "Antibiotic Resistance, Multi-Country Public Awareness Survey" was used. Data were collected across 14 states in Malaysia. (3) Results: A total of 517 participants completed the questionnaire. Most participants were females (67.9%), aged 30–49 (46%), and from central Malaysia (69.8%). Most participants (98.5%) reported taking antibiotics. A misconception presented was that sore throats, fevers, colds, and flu can be treated with antibiotics. A total of 58.8% of participants had high knowledge of antibiotic usage (scores 12–15), while 64% had high knowledge of antibiotic resistance (scores 9–14). Findings indicate that increasing age, income, and education were associated with higher knowledge. (4) Conclusions: This study highlights the knowledge deficiency of antibiotic resistance among Malaysians. Educational programs should engage a younger and lower socio-economic population to increase awareness. [ABSTRACT FROM AUTHOR]

Background: The emphasis on sustainable good health through the consumption of a healthy diet has necessitated the consumption of fresh vegetables, which could harbour the presence of members of the Enterobacteriaceae, antibiotic resistance and extendedspectrum beta-lactamase (ESBL). As a result, this study investigated the presence of antibiotics resistance (AR) and ESBL in Enterobacteriaceae isolated from garden eggs. Methodology: One hundred (100) garden egg samples were randomly purchased from 10 different vendors into sterile bags. Samples were serially diluted and cultured on MacConkey agar for the isolation of Enterobacteriaceae, then characterised and identified. Antibiotic susceptibility test was carried out on isolates following the Kirby-Bauer disc diffusion method. Double disc synergy test (DDST) was used to detect ESBL production. Result: Forty-three isolates were identified to belong to the family Enterobacteriaceae with Klebsiella spp. being the most dominant specie (51.16%), Escherichia coli (30.23%), Salmonella (11.23%) and Enterobacter aerogenes (6.98%). Of all the isolates, (65.12%) were multi-drug resistant (MDR). The isolates showed highest frequency of resistance to erythromycin (90.7%), gentamicin (34.9%), sulfamethoxazole/trimethoprim (32.6%), ofloxacin (30.2%), ciprofloxacin (25.6%), imipenem (14%), ceftriaxone (11.6%) and nalidixic acid (0.0%). For ESBL production, 23(53.49%) were positive. The ESBL positive isolates (n=23) were Klebsiella spp. 14(60.87%) and Escherichia coli 9 (39.13%). No ESBL production was detected in Salmonella spp. and Enterobacter aerogenes isolates. Conclusion: This study detected the presence of AR and ESBL in Enterobacteriaceae from garden eggs. Consumption of garden eggs contaminated with these bacteria pose a potential problem of infection and spread of resistance in the environment through food. [ABSTRACT FROM AUTHOR]

Cholera, a disease of antiquity, is still festering in developing countries that lack safe drinking water and sewage disposal. Vibrio cholerae, the causative agent of cholera, has developed multi-drug resistance to many antimicrobial agents. In aquatic habitats, phages are known to influence the occurrence and dispersion of pathogenic V. cholerae. We isolated Vibrio phage VMJ710 from a community sewage water sample of Manimajra, Chandigarh, in 2015 during an outbreak of cholera. It lysed 46% of multidrug-resistant V. cholerae O1 strains. It had significantly reduced the bacterial density within the first 4–6 h of treatment at the three multiplicity of infection (MOI 0.01, 0.1, and 1.0) values used. No bacterial resistance was observed against phage VMJ710 for 20 h in the time–kill assay. It is nearest to an ICP1 phage, i.e., Vibrio phage ICP1_2012 (MH310936.1), belonging to the class Caudoviricetes. ICP1 phages have been the dominant bacteriophages found in cholera patients' stools since 2001. Comparative genome analysis of phage VMJ710 and related phages indicated a high level of genetic conservation. The phage was stable over a wide range of temperatures and pH, which will be an advantage for applications in different environmental settings. The phage VMJ710 showed a reduction in biofilm mass growth, bacterial dispersal, and a clear disruption of bacterial biofilm structure. We further tested the phage VMJ710 for its potential therapeutic and prophylactic properties using infant BALB/c mice. Bacterial counts were reduced significantly when phages were administered before and after the challenge of orogastric inoculation with V. cholerae serotype O1. A comprehensive whole genome study revealed no indication of lysogenic genes, genes associated with possible virulence factors, or antibiotic resistance. Based on all these properties, phage VMJ710 can be a suitable candidate for oral phage administration and could be a viable method of combatting cholera infection caused by MDR V. cholerae pathogenic strains. [ABSTRACT FROM AUTHOR]

Campylobacter species are among the aetiological agents responsible for 400–500 million human diarrhoea cases per annum. The risk of dissemination of antibiotic-resistant Campylobacter species between humans, animals, and the environment is anticipated, given its transmissibility through these sources. The objective of this paper is to present a situation analysis that reports the current patterns and determinants of Campylobacter antibiotic resistance in South Africa. This review applies the One Health (OH) Approach to systematically review and collate the current antibiotic resistance status among Campylobacter spp. in South Africa. The highest level of resistance of Campylobacter in humans is to azithromycin (69.7%), whereas the lowest level of resistance of Campylobacter is to gatifloxacin (8.3%). In animals, high resistance to common antibiotics erythromycin (95.06%), clindamycin (95.68%), doxycycline (87.65%), erythromycin (90%), tetracycline (84.3%), streptomycin (88%), and ampicillin (73%) while 100% resistance of Campylobacter from water samples to tetracycline, imipenem, is recorded. Furthermore, resistance to clarithromycin (95%), azithromycin (92%), clindamycin (84.2%), doxycycline (80%), and ciprofloxacin (77.8%) is reported among Campylobacter spp. from water samples. The genetic similarity results suggest the movement of antibiotic-resistant Campylobacter spp. between humans and the environment. More research on antibiotic resistance among Campylobacter from other sources, outside clinical isolates, is recommended. HIGHLIGHTS High antibiotic resistance among Campylobacter isolates from humans, animals, and water in South Africa is observed.; There is an increased risk of waterborne antibiotic-resistant Campylobacter infections for communities that rely on the rivers for domestic and agricultural (irrigation) purposes.; More investigations of antibiotic resistance in Campylobacter of aquatic environmental origin are emphasised.;

Antibiotic resistance is a major risk to human health worldwide due to antibiotic- and multidrug-resistant bacteria, especially in the case of serious infections, which limits the availability of antimicrobial treatment options. Focusing on the bacterial resistance mechanisms against antibiotics and the conventional strategies used to combat antimicrobial resistance, this review highlights the history of antibiotics and their target mechanisms, mentions the strategy limitations, provides the most recent novel alternative therapies to combat resistance, and illustrates their mode of action and applications that may treat several infectious diseases caused by bacterial resistance. Finally, this paper mentions future prospects that we believe would make a considerable difference in the microbial resistance battle. Novel antibiotic alternative therapies, including nanomaterial therapy, antimicrobial photodynamic therapy, hybrid antimicrobial therapy, and phage therapy, are covered in this review.

Background: Hospitals with their high antimicrobial selection pressure represent the presumably most important reservoir of multidrug-resistant human pathogens. Antibiotics administered in the course of treatment are excreted and discharged into the wastewater system. Not only in patients, but also in the sewers, antimicrobial substances exert selection pressure on existing bacteria and promote the emergence and dissemination of multidrug-resistant clones. In previous studies, two main clusters were identified in all sections of the hospital wastewater network that was investigated, one K. pneumoniae ST147 cluster encoding NDM- and OXA-48 carbapenemases and one VIM-encoding P. aeruginosa ST823 cluster. In the current study, we investigated if NDM- and OXA-48-encoding K. pneumoniae and VIM-encoding P. aeruginosa isolates recovered between 2014 and 2021 from oncological patients belonged to those same clusters. Methods: The 32 isolates were re-cultured, whole-genome sequenced, phenotypically tested for their antimicrobial susceptibility, and analyzed for clonality and resistance genes in silico. Results: Among these strains, 25 belonged to the two clusters that had been predominant in the wastewater, while two others belonged to a sequence-type less prominently detected in the drains of the patient rooms. Conclusion: Patients constantly exposed to antibiotics can, in interaction with their persistently antibiotic-exposed sanitary facilities, form a niche that might be supportive for the emergence, the development, the dissemination, and the maintenance of certain nosocomial pathogen populations in the hospital, due to antibiotic-induced selection pressure. Technical and infection control solutions might help preventing transmission of microorganisms from the wastewater system to the patient and vice versa, particularly concerning the shower and toilet drainage. However, a major driving force might also be antibiotic induced selection pressure and parallel antimicrobial stewardship efforts could be essential. [ABSTRACT FROM AUTHOR]

Antibiotic resistance poses a significant threat to the global health, food security, and environment. In poultry and livestock, antibiotics are beneficial since they improve poultry performance and are economically effective. Therefore, it is crucial to search for alternatives that can be environmentally safe and successful in treating these infections. In this study, we employed molecular docking to evaluate lemon peel phytochemical’s protein binding capability against various poultry pathogens. The nanoparticles (LP AgNPs) obtained from the lemon peel were characterized and tested for their antibacterial activity against more poultry pathogens. LP AgNPs were characterized by using UV–Visible absorption spectra, which revealed an absorption peak at a wavelength of 420–440 nm. The FT–IR analysis demonstrated that flavonoids and phenolic acids acted as capping, reducing, and stabilizing agents during the biosynthesis of AgNPs. EDAX showed a strong peak was observed at 3 keV which revealed the absorption of metallic silver nanoparticles. The mean diameter was from 2 to 20 nm through HRTEM. Zeta potential of the LP AgNps at − 17.2 mV showed the high stability of the green synthesized AgNps. Maximum inhibitory concentrations of LP AgNps against the isolated poultry pathogens were 50 μg/ml concentration. The toxicity tests were performed in the Vigna radiata seedlings and Artemia nauplii, which showed less toxic effects and eco-friendly nature of the LP AgNps. LP AgNps have the potential to treat antibiotic resistant poultry pathogens, thereby paving the way for the development of value-added novel products incorporated with nanoparticles for treating various infection caused by antibiotic-resistant poultry pathogens. [ABSTRACT FROM AUTHOR]

Simple Summary: Biochanin A is an isoflavone, a small molecule produced by red clover (Trifolium pratense) and other legumes. Biochanin A promoted weight gain in growing steers in a manner similar to feed antibiotics. In laboratory experiments, biochanin A prevented bacteria from pumping out antibiotics and other inhibitory compounds, which increased their sensitivity to those inhibitors. It seemed logical that biochanin A might reduce the number of bacteria that were insensitive to an inhibitor, for example, the antibiotic tetracycline. The number of tetracycline-insensitive bacteria in the bovine rumen increases when the animals are fed high-starch diets. We fed steers (Bos taurus) diets with increasing concentrations of cracked corn (Zea mays) and enumerated the tetracycline-insensitive bacteria. Experimental groups received (1) biochanin A, (2) a well-studied feed antimicrobial, (3) no intervention, or (4) they were left on a forage-only diet. Biochanin A mitigated the increase in tetracycline-insensitive bacteria during the high-starch periods. These results support the idea that biochanin A can make some bacteria more sensitive to antibiotics and other inhibitors in animals, just as it does in the laboratory. More research is needed to determine the roles of forage legumes as alternatives to growth-promoting antibiotics and in combating the spread of antibiotic-resistant bacteria. The isoflavone biochanin A was previously shown to promote weight gain in growing steers by selectively inhibiting rumen bacteria-like growth-promoting feed antibiotics. The hypothesis that biochanin A inhibited the action of drug efflux pumps was tested by enumerating tetracycline-insensitive bacteria from steers in a subacute rumen acidosis (SARA) challenge. Steers (n = 3/group) treatment groups were forage only, SARA control, SARA with monensin (0.2 g d−1), and SARA with biochanin A (6.0 g d−1). As the steers were stepped up from the forage-only basal diet to 70% cracked corn, the number of rumen bacteria enumerated on two tetracycline-containing media types (nutrient glucose agar and tetracycline, and bile esculin azide and tetracycline) increased (p < 0.05) from as little as 1.7(105) to as great as 6.7(106) cfu mL−1 on the nutrient glucose agar in the SARA and monensin control groups. The biochanin A group maintained the same number of tetracycline-insensitive bacteria as the forage-only controls (p > 0.05). The effects were similar to the more selective media type, but the differences were smaller. These results support the hypothesis that biochanin A inhibits the activity of drug efflux pumps in vivo. [ABSTRACT FROM AUTHOR]

As warned by Sir Alexander Fleming in his Nobel Prize address: "the use of antimicrobials can, and will, lead to resistance". Antimicrobial resistance (AMR) has recently increased due to the overuse and misuse of antibiotics, and their use in animals (food-producing and companion) has also resulted in the selection and transmission of resistant bacteria. The epidemiology of resistance is complex, and factors other than the overall quantity of antibiotics consumed may influence it. Nowadays, AMR has a serious impact on society, both economically and in terms of healthcare. This narrative review aimed to provide a scenario of the state of the AMR phenomenon in veterinary medicine related to the use of antibiotics in different animal species; the impact that it can have on animals, as well as humans and the environment, was considered. Providing some particular instances, the authors tried to explain the vastness of the phenomenon of AMR in veterinary medicine due to many and diverse aspects that cannot always be controlled. The veterinarian is the main reference point here and has a high responsibility towards the human–animal–environment triad. Sharing such a burden with human medicine and cooperating together for the same purpose (fighting and containing AMR) represents an effective example of the application of the One Health approach. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is an issue of growing importance in the public health sphere. Medical interns are of great relevance when it comes to the source of this problem. This study therefore sought to ascertain which factors influence the management of antibiotic therapy by this population, in order to pinpoint the possible causes of misprescribing habits. We conducted a qualitative study based on focus group techniques, with groups consisting of medical interns from the Santiago de Compostela Clinical University Teaching Hospital. Our study identified factors which the participants considered to be determinants of antibiotic use and their relationship with the appearance of resistance. The single most repeated factor was the influence of the attending physician's judgement; other factors included a high healthcare burden or prescribing inertia. This stage is an opportunity to correct misprescribing habits, by implementing educational interventions aimed at modifying the identified factors. [ABSTRACT FROM AUTHOR]

Antibiotic resistance in foodborne pathogens is an increasing threat to global human health. Among the most prevalent antibiotic-resistant bacteria are Salmonella enterica serovar Typhimurium, Campylobacter jejuni and E. coli 0157:H7. Control of these and other pathogens requires innovative approaches, i.e., discovering new molecules that will inactivate them, or render them less virulent without inducing resistance. Recently, several polyphenol molecules have been shown to possess such characteristics. Also, the use of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) approaches has recently been proposed for such purpose. This review summarizes the main findings regarding the application of both approaches to control the above-mentioned foodborne pathogens by relying on Quorum Sensing interference (Quorum Quenching) mechanisms and highlights the avenues needed for further research.

Background: Neisseria gonorrhoeae is a gram negative diplococci which causess a sexually transmitted infection. N. gonorrhoeae is an obligate human pathogen that causes infection to the mucus-secreting epithelial cells both in male and female. In 2017, the centre of disease control and World Health Organization published the list of global priority pathogens with denting therapeutic options, including antibiotic-resistant N. gonorrhoeae. During the covid-19 pandemic, excessive use of antibiotics led to raise of drug resistance. The infection is widespread and intractable. If this happens, more people will be left with an incurable infection which may cause serious health problems. Results: We characterized zoliflodacin thoroughly. Here is discussed the clinical trials and side effects on human health by searching different keywords like “zoliflodacin”, “covid-19”, “clinical trials” from different data sources like Pub-Med, Google-Scholar, and Science-Direct. Zoliflodacin targets antibiotic-resistant N. gonorrhoeae. Zoliflodacin is mainly known based on its therapeutic effects against N. gonorrhoeae. It acts by inhibiting bacterial type 2 topoisomerase with binding site in bacterial gyrase. Zoliflodacin is effective in treating gonococcal urogenital and rectal infection. Conclusion: Antibiotic is the only option to treat N. gonorrhoeae. There is no vaccine available to treat gonorrhea. The new drug, zoliflodacin, specifically targets antibiotic-resistant gonorrhea and its is why researchers have studied this antibiotic from different point of views. In this study, we elaborate the discovery of zoliflodacin, its mechanism of action, the current clinical trials, and the effectiveness of zoliflodacin.

Most human infectious diseases are caused by microorganisms growing as biofilms. These three-dimensional self-organized communities are embedded in a dense matrix allowing microorganisms to persistently inhabit abiotic and biotic surfaces due to increased resistance to both antibiotics and effectors of the immune system. Consequently, there is an urgent need for novel strategies to control biofilm-associated infections. Natural products offer a vast array of chemical structures and possess a wide variety of biological properties; therefore, they have been and continue to be exploited in the search for potential biofilm inhibitors with a specific or multi-locus mechanism of action. This review provides an updated discussion of the major bioactive compounds isolated from several natural sources – such as plants, lichens, algae, microorganisms, animals, and humans – with the potential to inhibit biofilm formation and/or to disperse established biofilms by bacterial pathogens. Despite the very large number of bioactive products, their exact mechanism of action often remains to be clarified and, in some cases, the identity of the active molecule is still unknown. This knowledge gap should be filled thus allowing development of these products not only as novel drugs to combat bacterial biofilms, but also as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics. [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile is the most common cause of healthcare-associated infections in the United States. It is unknown whether universal gown and glove use in intensive care units (ICUs) decreases acquisition of C. difficile. Methods This was a secondary analysis of a cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from 4 January 2012 to 4 October 2012. After a baseline period, ICUs were randomized to standard practice for glove and gown use versus the intervention of all healthcare workers being required to wear gloves and gowns for all patient contact and when entering any patient room (contact precautions). The primary outcome was acquisition of toxigenic C. difficile determined by surveillance cultures collected on admission and discharge from the ICU. Results A total of 21 845 patients had both admission and discharge perianal swabs cultured for toxigenic C. difficile. On admission, 9.43% (2060/21 845) of patients were colonized with toxigenic C. difficile. No significant difference was observed in the rate of toxigenic C. difficile acquisition with universal gown and glove use. Differences in acquisition rates in the study period compared with the baseline period in control ICUs were 1.49 per 100 patient-days versus 1.68 per 100 patient-days in universal gown and glove ICUs (rate difference, −0.28; generalized linear mixed model, P =.091). Conclusions Glove and gown use for all patient contact in medical and surgical ICUs did not result in a reduction in the acquisition of C. difficile compared with usual care. Clinical Trials Registration NCT01318213. [ABSTRACT FROM AUTHOR]

Bivalve shellfish consumption (ark shells, clams, cockles, and oysters) has increased over the last decades. Following this trend, infectious disease outbreaks associated with their consumption have been reported more frequently. Molluscs are a diverse group of organisms found wild and farmed. They are common on our tables, but unfortunately, despite their great taste, they can also pose a threat as a potential vector for numerous species of pathogenic microorganisms. Clams, in particular, might be filled with pathogens because of their filter-feeding diet. This specific way of feeding favors the accumulation of excessive amounts of pathogenic microorganisms like Vibrio spp., including Vibrio cholerae and V. parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Arcobacter spp., and fecal coliforms, and intestinal enterococci. The problems of pathogen dissemination and disease outbreaks caused by exogenous bacteria in many geographical regions quickly became an unwanted effect of globalized food supply chains, global climate change, and natural pathogen transmission dynamics. Moreover, some pathogens like Shewanella spp., with high zoonotic potential, are spreading worldwide along with food transport. These bacteria, contained in food, are also responsible for the potential transmission of antibiotic-resistance genes to species belonging to the human microbiota. Finally, they end up in wastewater, thus colonizing new areas, which enables them to introduce new antibiotic-resistance genes (ARG) into the environment and extend the existing spectrum of ARGs already present in local biomes. Foodborne pathogens require modern methods of detection. Similarly, detecting ARGs is necessary to prevent resistance dissemination in new environments, thus preventing future outbreaks, which could threaten associated consumers and workers in the food processing industry. [ABSTRACT FROM AUTHOR]

Campylobacter species are among the aetiological agents responsible for 400-500 million human diarrhoea cases per annum. The risk of dissemination of antibiotic-resistant Campylobacter species between humans, animals, and the environment is anticipated, given its trans- missibility through these sources. The objective of this paper is to present a situation analysis that reports the current patterns and determinants of Campylobacter antibiotic resistance in South Africa. This review applies the One Health (OH) Approach to systematically review and collate the current antibiotic resistance status among Campylobacter spp. in South Africa. The highest level of resistance of Campylobacter in humans is to azithromycin (69.7%), whereas the lowest level of resistance of Campylobacter is to gatifloxacin (8.3%). In animals, high resistance to common antibiotics erythromycin (95.06%), clindamycin (95.68%), doxycycline (87.65%), erythromycin (90%), tetracycline (84.3%), streptomycin (88%), and ampicillin (73%) while 100% resistance of Campylobacter from water samples to tetracycline, imipenem, is recorded. Furthermore, resistance to clarithromycin (95%), azithromycin (92%), clindamycin (84.2%), doxycycline (80%), and ciprofloxacin (77.8%) is reported among Campylobacter spp. from water samples. The genetic similarity results suggest the movement of antibiotic-resistant Campylobacter spp. between humans and the environment. More research on antibiotic resistance among Campylobacter from other sources, outside clinical isolates, is recommended. [ABSTRACT FROM AUTHOR]

The occurrence of antibiotics in the environment could result in the development of antibiotic-resistant bacteria, which could result in a public health crisis. The occurrence of 676 antibiotics and the main transformation products (TPs) was investigated in the 48 wastewater treatment plants (WWTPs) from 11 countries (Germany, Romania, Serbia, Croatia, Slovenia, Hungary, Slovakia, Czechia, Austria, Cyprus, and Greece) by target and suspect screening. Target screening involved the investigation of antibiotics with reference standards (40 antibiotics). Suspect screening covered 676 antibiotics retrieved from the NORMAN Substance Database (antibiotic list on NORMAN network). Forty-seven antibiotics were detected in effluent wastewater samples: thirty-two by target screening and fifteen additional ones by suspect screening. An ecotoxicological risk assessment was performed based on occurrence data and predicted no effect concentration (PNEC), which involved the derivation of frequency of appearance (FoA), frequency of PNEC exceedance (FoE), and extent of PNEC exceedance (EoE). Azithromycin, erythromycin, clarithromycin, ofloxacin, and ciprofloxacin were prioritized as the calculated risk score was above 1. The median of antibiotics' load to freshwater ecosystems was 0.59 g/day/WWTP. The detection of antibiotics across countries indicates the presence of antibiotics in the ecosystems of Europe, which may trigger unwanted responses from the ecosystem, including antibiotic resistance. [ABSTRACT FROM AUTHOR]

New Delhi metallo‐β‐lactamase (NDM‐1) that can hydrolyze almost all clinical β‐lactam antibacterial causes "Super" bacterial infection, which seriously threatens human health worldwide. Therefore, it is urgent to establish powerful methods for inhibiting NDM‐1 activity and efficient anti‐resistant bacteria. Herein, a new strategy for the depression of NDM‐1 activity and synergistic therapy to overcome drug‐resistant bacteria based on conjugated oligomer (OPV)‐modified porphyrin derivatives OPV‐C6‐TPP probe is developed. The unimolecular probe not only can coordinate Zn2+ in NDM‐1 to suppress the activity of NDM‐1 but also produce the high 1O2 under light irradiation, providing dual functions of activating antibiotics and photodynamic therapy. The chelation inhibition mechanism of OPV‐C6‐TPP on NDM‐1 is investigated and further confirmed by molecular docking and molecular dynamics simulation studies. In the presence of probe, the minimum inhibitory concentration of antibiotic model cefazolin is reduced ≈50 times, significantly reversing resistance and resensitizing NDM‐1‐overexpressing Escherichia coli (E. coli‐NDM‐1) to antibiotics. Furthermore, the combined system greatly accelerates wound healing in E. coli‐NDM‐1 infected mice due to photodynamic and antibiotic synergistic effects. This study paves the way for the efficient treatment of drug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a major risk to human health worldwide due to antibiotic- and multidrugresistant bacteria, especially in the case of serious infections, which limits the availability of antimicrobial treatment options. Focusing on the bacterial resistance mechanisms against antibiotics and the conventional strategies used to combat antimicrobial resistance, this review highlights the history of antibiotics and their target mechanisms, mentions the strategy limitations, provides the most recent novel alternative therapies to combat resistance, and illustrates their mode of action and applications that may treat several infectious diseases caused by bacterial resistance. Finally, this paper mentions future prospects that we believe would make a considerable difference in the microbial resistance battle. Novel antibiotic alternative therapies, including nanomaterial therapy, antimicrobial photodynamic therapy, hybrid antimicrobial therapy, and phage therapy, are covered in this review. [ABSTRACT FROM AUTHOR]

Amikacin is an aminoglycoside antibiotic used in drug-resistant bacterial infections. The spread of bacterial infections has become a severe concern for the treatment system because of the simultaneous drug resistance bacteria and SARS-CoV-2 hospitalized patients. One of the most common bacteria in the development of drug resistance is Klebsiella strains, which is a severe threat due to the possibility of biofilm production. In this regard, recent nanotechnology studies have proposed using nanocarriers as a practical proposal to improve the performance of antibiotics and combat drug resistance. Among drug nanocarriers, niosomes are considered for their absorption mechanism, drug coverage, and biocompatibility. In this study, niosomal formulations were synthesized by the thin-layer method. After optimizing the synthesized niosomes, their properties were evaluated in terms of stability and drug release rate. The toxicity of the optimal formulation was then analyzed. The effect of free amikacin and amikacin encapsulated in niosome on biofilm inhibition were compared in multi-drug resistant isolated Klebsiella strains, and the mrkD gene expression was calculated. The MIC and MBC were measured for the free drug and amikacin loaded in the noisome. The particle size of synthesized amikacin-loaded niosomes ranged from 175.2 to 248.3 nm. The results showed that the amount of lipid and the molar ratio of tween 60 to span 60 has a positive effect on particle size, while the molar ratio of surfactant to cholesterol has a negative effect. The highest release rate in amikacin-loaded niosomes is visible in the first 8 h, and then a slower release occurs up to 72 h. The cytotoxicity induced by amikacin-loaded niosome is significantly less than the cytotoxicity of free amikacin in HFF cells (***p < 0.001, **p < 0.01). The mrkD mRNA expression level in the studied strains was significantly reduced after treatment with niosome-containing amikacin compared to free amikacin (***p < 0.001). It was confirmed that in the presence of the niosome, the amikacin antibacterial activity increased while the concentration of the drug used decreased, the formation of biofilm inhibited, and reduced antibiotics resistance in MDR Klebsiella strains. [ABSTRACT FROM AUTHOR]

Abstract Background The indiscriminate use and the similarity of prescribed antibiotics especially beta-lactams in human and small animal medicine, along with the close communication between pets and humans, increases the risk of the transfer of antibiotic-resistant bacteria and/or resistance elements especially integrons, between them. Therefore, we aimed to compare the frequencies of extended spectrum beta-lactamase (ESBL)-producing strains, major ESBL genes, classes 1 and 2 integrons, and antibiotic resistance patterns of fecal Escherichia coli (E. coli) isolates from dogs and their owners. Methods The present study was conducted on 144 commensal E. coli isolates from the feces of 28 healthy dog-owner pairs and 16 healthy humans who did not own pets. Phenotypic confirmatory test was used to identify the frequencies of ESBL-producing E. coli. Frequencies of bla CTX-M, bla SHV, and bla TEM genes, and also classes 1 and 2 integrons were determined by polymerase chain reaction. Resistance against 16 conventional antibiotics was determined by disk diffusion technique. Results ESBL-production status was similar between the E. coli isolates of 71.4% of dog-owner pairs. The E. coli isolates of 75, 60.7, and 85.7% of dog-owner pairs were similar in terms of the presence or absence of bla CTX-M, bla TEM, and bla SHV genes, respectively. The presence or absence of class 1 and class 2 integrons was the same in E. coli isolates of 57.1% of dog-owner pairs. Prevalence of resistance to chloramphenicol and tetracycline was significantly higher in E. coli isolates of dogs than owners, but for other 10 (83.3%) tested antibiotics, no statistically significant difference was found in prevalence of antibiotic resistance between dogs and owners isolates. Furthermore, the antibiotic-resistance profile was the same in the E. coli isolates of 14.3% of dog-owner pairs. Conclusions The results of current research highlight the seriousness of the drug-resistance problem and the need to prevent further increases and spread of antibiotic-resistance to reduce treatment failure. Moreover, relatively similar characteristics of the E. coli isolates of dogs and their owners can show the risk of sharing resistant bacteria and/or resistance elements between them.

[Display omitted] • Sensing tool for identifying antimicrobial-resistant Staphylococcus aureus strains. • Fluorescent sensor array pre-adsorbed on paper microzone plates for better efficiency. • Classification of laboratory and clinical S. aureus strains powered by machine learning. • Sensor identifies biofilms associated with antimicrobial-resistant S. aureus strains. • Rapid, low-volume identification with >90% classification accuracy. Staphylococcus aureus , a versatile human pathogen, significantly impacts global health causing a broad spectrum of medical conditions that range from minor skin infections to life-threatening diseases. The clinical importance of S. aureus is underscored by its resistance to multiple antibiotics and formation of biofilms, providing protection against antimicrobials and immune responses. To date, the identification of antimicrobial-resistant (AMR) S. aureus strains, such as methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA), requires time-consuming and expensive methodologies, including culture-based, molecular, and phenotypic techniques. Previously, we developed a paper-based ratiometric sensor array composed of fluorescent sensor dyes (3-hydroxyflavone derivatives) pre-adsorbed on paper microzone plates. Combined with machine learning algorithms such as neural networks, this sensor effectively discriminated 16 bacterial species and determined their Gram status. In this study, we evaluate its ability to distinguish antibiotic-resistant S. aureus strains and their biofilms. Our results demonstrate that the sensor array, in conjunction with LDA and neural networks, successfully differentiated three common laboratory MRSA strains from three methicillin-susceptible S. aureus (MSSA) strains with 82.5% accuracy. Furthermore, using support vector machines, this sensor was able to distinguish and categorically classify MRSA, MSSA, and VISA clinical isolates with 97.5% accuracy. Remarkably, beyond distinguishing planktonic cultures, this sensor array demonstrated a formidable capability to discriminate AMR S. aureus biofilms, achieving over 80% accuracy. Combined, the results of this study highlight the paper-based sensor array's significant potential as a robust diagnostic tool to accurately, rapidly, and easily identify drug-resistant S. aureus strains in clinically relevant settings. [ABSTRACT FROM AUTHOR]

In this work, the antibiotic resistance, biofilm formation capability, and clonal relatedness of 50 A. baumannii isolates collected from three hospitals in Ardabil city, Iran, were evaluated. Antibiotic sensitivity and biofilm formation of isolates were determined by disk diffusion and microtiter-plate methods, respectively. Molecular typing of isolates was also performed using repetitive sequence-based PCR (REP-PCR). The majority of isolates were resistant to cephems, aminoglycosides, and carbapenems, with 80 % classified as multi-drug resistant (MDR). While, only isolates collected from blood and tracheal were resistant to colistin. Additionally, 42 isolates (84 %) had biofilm formation capability. According to rep-PCR results, 34 isolates showed similar banding patterns, while 16 isolates had unique banding patterns. Finally, based on the molecular analysis, there was a direct relationship between biofilm formation and the antibiotic resistance of isolates. In other words, MDR isolates had a higher ability to form biofilm. • The clonal characteristics of Acinetobacter baumannii isolates were examined. • There was direct relationship between biofilm formation and antibiotic resistance. • Antibiotic colistin can be successfully used against the growth of isolates. [ABSTRACT FROM AUTHOR]

Objective: To determine the inhibition mechanisms of secretome protein extracted from Paenibacillus polymyxa Kp10 (Kp10) and Lactococcus lactis Gh1 (Gh1) against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Methods: The sensitivity and viability of MRSA and VRE treated with secretome proteins of Kp10 and Gh1 were determined using minimal inhibitory concentration, minimum bactericidal concentration, and time-to-kill assays. The morphological changes were observed using scanning electron microscopy and transmission electron microscopy. To elucidate the antimicrobial mechanism of secretome protein of Kp10 and Gh1 against MRSA and VRE, 2D gel proteomic analysis using liquid chromatography-mass spectrometry was run by comparing upregulated and downregulated proteins, and the proton motive force study including the efflux of ATP, pH gradient, and the membrane potential study were conducted. Results: MRSA and VRE were sensitive to Kp10 and Gh1 secretome protein extracts and displayed apparent morphological and internal composition changes. Several proteins associated with cellular component functions were either downregulated or upregulated in treated MRSA and VRE by changing the membrane potential gradient. Conclusions: Kp10 and Gh1 secretome proteins reduce the growth of VRE and MRSA by damaging the cell membrane. Cell division, cell wall biosynthesis, and protein synthesis are involved in the inhibition mechanism.

Abstract Bacillus velezensis SK having broad-spectrum antimicrobial activity has been isolated from soil. The efficient extraction of antimicrobial compounds produced in various mediums has been done using Diaion HP-20 resin. Further, characterization of an antimicrobial compound by TLC, FTIR, in-situ bioautography analysis revealed the presence of cyclic lipopeptides, which is then purified by the combination of silica gel, size exclusion, dual gradient, and RP-HPLC chromatography techniques. Growth kinetic studies showed that Bacillus velezensis SK produces a mixture of lipopeptides (1.33 gL−1). The lipopeptide exhibits good pH (2–10) and temperature stability up to 80 °C. LC–ESI–MS analysis of partially purified lipopeptide identified variant of surfactin, further analysis of purified chromatographic fractions revealed the occurrence of most abundant C15-surfactin homologues (m/z 1036.72 Da). The isolated surfactin exhibits good antimicrobial activity (1600 AU/ml) against drug-resistant food-born B. cereus and human pathogen Staphylococcus aureus. Hence, identified strain B. velezensis SK and its potent antibacterial surfactin lipopeptide could be used in various food and biomedical applications.

Due to the increased resistance to all available antibiotics and the lack of vaccines, Neisseria gonorrhoeae (the gonococcus) poses an urgent threat. Although the mechanisms of virulence and antibiotic resistance have been largely investigated in this bacterium, very few studies have addressed the stringent response (SR) that in pathogenic bacteria controls the expression of genes involved in host-pathogen interaction and tolerance and persistence toward antibiotics. In this study, the results of the transcriptome analysis of a clinical isolate of N. gonorrhoeae, after induction of the SR by serine hydroxamate, provided us with an accurate list of genes that are transcriptionally modulated during the SR. The list includes genes associated with metabolism, cellular machine functions, host-pathogen interaction, genome plasticity, and antibiotic tolerance and persistence. Moreover, we found that the artificial induction of the SR in N. gonorrhoeae by serine hydroxamate is prevented by thiostrepton, a thiopeptide antibiotic that is known to interact with ribosomal protein L11, thereby inhibiting functions of EF-Tu and EF-G, and binding of pppGpp synthase I (RelA) to ribosome upon entry of uncharged tRNA. We found that N. gonorrhoeae is highly sensitive to thiostrepton under in vitro conditions, and that thiostrepton, in contrast to other antibiotics, does not induce tolerance or persistence. Finally, we observed that thiostrepton attenuated the expression of key genes involved in the host-pathogen interaction. These properties make thiostrepton a good drug candidate for dampening bacterial virulence and preventing antibiotic tolerance and persistence. The ongoing challenge is to increase the bioavailability of thiostrepton through the use of chemistry and nanotechnology.

Bivalve shellfish consumption (ark shells, clams, cockles, and oysters) has increased over the last decades. Following this trend, infectious disease outbreaks associated with their consumption have been reported more frequently. Molluscs are a diverse group of organisms found wild and farmed. They are common on our tables, but unfortunately, despite their great taste, they can also pose a threat as a potential vector for numerous species of pathogenic microorganisms. Clams, in particular, might be filled with pathogens because of their filter-feeding diet. This specific way of feeding favors the accumulation of excessive amounts of pathogenic microorganisms like Vibrio spp., including Vibrio cholerae and V. parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Arcobacter spp., and fecal coliforms, and intestinal enterococci. The problems of pathogen dissemination and disease outbreaks caused by exogenous bacteria in many geographical regions quickly became an unwanted effect of globalized food supply chains, global climate change, and natural pathogen transmission dynamics. Moreover, some pathogens like Shewanella spp., with high zoonotic potential, are spreading worldwide along with food transport. These bacteria, contained in food, are also responsible for the potential transmission of antibiotic-resistance genes to species belonging to the human microbiota. Finally, they end up in wastewater, thus colonizing new areas, which enables them to introduce new antibiotic-resistance genes (ARG) into the environment and extend the existing spectrum of ARGs already present in local biomes. Foodborne pathogens require modern methods of detection. Similarly, detecting ARGs is necessary to prevent resistance dissemination in new environments, thus preventing future outbreaks, which could threaten associated consumers and workers in the food processing industry.

Bacterial small RNAs (sRNAs) research has accelerated over the past decade, boosted by advances in RNA-seq technologies and methodologies for capturing both protein–RNA and RNA–RNA interactions. The emerging picture is that these regulatory sRNAs play important roles in controlling complex physiological processes and are required to survive the antimicrobial challenge. In recent years, the RNA content of OMVs/EVs has also gained increasing attention, particularly in the context of infection. Secreted RNAs from several bacterial pathogens have been characterized but the exact mechanisms promoting pathogenicity remain elusive. In this review, we briefly discuss how secreted sRNAs interact with targets in infected cells, thus representing a novel perspective of host cell manipulation during bacterial infection. During the last decade, Acinetobacter baumannii became clinically relevant emerging pathogens responsible for nosocomial and community-acquired infections. Therefore, we also summarize recent findings of regulation by sRNAs in A. baumannii and discuss how this emerging bacterium utilizes many of these sRNAs to adapt to its niche and become successful human pathogen.

Living organisms are known to respond to various types of environmental stress factors. The response is observed when the magnitude of stress exceeds a minimum amount called threshold. However during the past few decades, response of the living organisms below the threshold came to the purview of the scientists. Some stress factors are found to elicit a biphasic response viz, stimulation at low dose and inhibition at high dose. The phenomenon called hormesis plays a crucial role in the acclimatization of organisms to the environment. Physical and chemical factors that elicit hormetic type responses are called hormetins. The importance of some chemicals that mimic the effect of hormetins in therapeutics is beginning to be understood. [ABSTRACT FROM AUTHOR]

Objective: To determine the inhibition mechanisms of secretome protein extracted from Paenibacillus polymyxa Kp10 (Kp10) and Lactococcus lactis Gh1 (Gh1) against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Methods: The sensitivity and viability of MRSA and VRE treated with secretome proteins of Kp10 and Gh1 were determined using minimal inhibitory concentration, minimum bactericidal concentration, and time-to-kill assays. The morphological changes were observed using scanning electron microscopy and transmission electron microscopy. To elucidate the antimicrobial mechanism of secretome protein of Kp10 and Gh1 against MRSA and VRE, 2D gel proteomic analysis using liquid chromatographymass spectrometry was run by comparing upregulated and downregulated proteins, and the proton motive force study including the efflux of ATP, pH gradient, and the membrane potential study were conducted. Results: MRSA and VRE were sensitive to Kp10 and Gh1 secretome protein extracts and displayed apparent morphological and internal composition changes. Several proteins associated with cellular component functions were either downregulated or upregulated in treated MRSA and VRE by changing the membrane potential gradient. Conclusions: Kp10 and Gh1 secretome proteins reduce the growth of VRE and MRSA by damaging the cell membrane. Cell division, cell wall biosynthesis, and protein synthesis are involved in the inhibition mechanism. [ABSTRACT FROM AUTHOR]