Antibiotic Resistance Research Articles

From past to present, exploring the applications of mupirocin ointment: A comprehensive review

Mupirocin (MUP), a potent antibacterial agent, has been a cornerstone of topical antimicrobial therapy for several decades. As an older, yet widely used antibiotic, MUP has exhibited efficacy against various bacterial strains, making it a versatile tool in the management of a range of infections. The review synthesizes available literature to highlight the evolution of MUP, from its initial discovery to its current status as a go-to topical antibiotic. In the era of rising antibiotic resistance, MUP is positioned as a valuable therapeutic option due to its broad-spectrum activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Emphasis is placed on its distinctive role in different infections, enhanced efficacy with different additives, and newer drug delivery strategies.In addition to its classical applications in impetigo and other superficial skin infections, this review delves into emerging indications and novel uses of MUP, potentially expanding its clinical utility. The exploration of combination therapies, alternative formulations, and ongoing research endeavors will contribute to a forward-looking perspective on the role of MUP in future antimicrobial strategies.

Antibiotic resistance and serotype distribution of Shigella strains in Bangladesh over the period of 2014–2022: evidence from a nationwide hospital-based surveillance for cholera and other diarrheal diseases

ABSTRACT The objective of this study was to assess the prevalence, antimicrobial resistance patterns, and risk factors linked to Shigella infections through a nationwide hospital-based diarrheal disease surveillance in Bangladesh. From May 2014 to May 2022, from a systematic sentinel surveillance of Shigella infections in over 10 hospitals across Bangladesh, stool specimens were collected from patients with acute watery diarrhea and tested for Shigella species by microbiological culture. The susceptibility to antibiotics was tested using the disk diffusion method. Structured questionnaires were used to collect participants’ socioeconomic status and clinical, sanitation, and food history. Out of 24,357 stool specimens, 1.8% were positive for Shigella species, with a higher prevalence among males (58%). Children in the 6–17 age group were found to be at the highest risk of Shigella infections. The most prevalent serotype was Shigella flexneri (79.5%), followed by Shigella sonnei. S. flexneri serotype 2a was the most common (63.3%) among all Shigella serotypes. Antibiotic susceptibility testing showed over 99% of isolates resistant or with intermediate susceptibility to one of the seven antibiotics tested. About 96% of S. flexneri and all S. sonnei isolates demonstrated resistance to at least one quinolone class of antibiotics, particularly ciprofloxacin or nalidixic acid. S. sonnei showed higher antibiotic resistance and multidrug resistance compared to S. flexneri . The high level of resistance to ciprofloxacin highlights the need for more prudent use of this antibiotic and improved hygiene and sanitation. The study emphasized the importance of regular monitoring of drug resistance to effectively manage Shigella infections. These findings may provide the epidemiological evidence for conducting future appropriate Shigella vaccine clinical trials in Bangladesh. IMPORTANCE This nationwide study in Bangladesh assessed Shigella infections from 2014 to 2022 from clinical samples. S. flexneri was predominant, with concerning antibiotic resistance, notably to ciprofloxacin and nalidixic acid in over 96% of isolates. This emphasizes the urgency of prudent antibiotic use and improved hygiene. The findings provide crucial antimicrobial resistance patterns of Shigella species, highlighting the need for ongoing resistance monitoring and potentially informing future vaccine trials.

The Impact of Urban Pollution on Plasmid-Mediated Resistance Acquisition in Enterobacteria from a Tropical River

Background: The exposure of environmental bacteria to contaminants in aquatic ecosystems accelerates the dissemination of antibiotic-resistance genes (ARGs) through horizontal gene transfer (HGT). Methods: In this study, we sampled three locations along a contamination gradient of a polluted river, focusing on isolating Enterobacteria from the surface waters to investigate the relationship between urban pollution and antibiotic resistance. The genomes of 15 isolates (5 per site) were sequenced to identify plasmid-borne ARGs and their association with resistance phenotypes. Results: Isolates from the site with the highest contamination (Site 3) showeda larger number of ARGs, plasmids, and resistance phenotypes. Notably, one of the isolates analyzed, E. coli A231-12, exhibited phenotypic resistance to seven antibiotics, presumably conferred by a single plasmid carrying 12 ARGs. Comparative analysis of this plasmid revealed its close evolutionary relationship with another IncH plasmid hosted by Salmonella enterica, underscoring its high ARG burden in the aquatic environment. Other plasmids identified in our isolates carried sul and dfrA genes, conferring resistance to trimethoprim/sulfamethoxazole, a commonly prescribed antibiotic combination in clinical settings. Conclusions: These results highlight the critical need to expand research on the link between pollution and plasmid-mediated antimicrobial resistance in aquatic ecosystems, which can act as reservoirs of ARGs.

Evolutionary trajectories of β-lactam resistance in Enterococcus faecalis strains

ABSTRACT Resistance to ampicillin and imipenem in Enterococcus faecalis is infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a long-term evolution experiment using four genetically diverse strains of E. faecalis with varying susceptibilities to ampicillin and imipenem. Each strain was subjected to increasing concentrations of either ampicillin or imipenem over 200 days, with three independent replicates for each strain. Selective pressure from imipenem led to the rapid selection of highly resistant lineages across all genetic backgrounds, compared to ampicillin. In addition to high resistance, we describe, for the first time, the evolution of a β-lactam-dependent phenotype observed in lineages from all backgrounds. Whole-genome sequencing and bioinformatic analysis revealed mutations in three main functional classes: genes involved in cell wall synthesis and degradation, genes in the walK/R two-component system, and genes in the c-di-AMP pathway. Our analysis identified new mutations in genes known to be involved in resistance as well as novel genes potentially associated with resistance. Furthermore, the newly described β-lactam-dependent phenotype was correlated with the inactivation of c-di-AMP degradation, resulting in high levels of this second messenger. Together, these data highlight the diverse genetic mechanisms underlying resistance to ampicillin and imipenem in E. faecalis . The emergence of high resistance levels and β-lactam dependency underscores the importance of understanding evolutionary dynamics in the development of antibiotic resistance. IMPORTANCE Enterococcus faecalis is a major human pathogen, and treatment is frequently compromised by poor response to first-line antibiotics such as ampicillin. Understanding the factors that play a role in susceptibility/resistance to these drugs will help guide the development of much-needed treatments.

Investigation of Antibiotic Resistance of E. coli Associated with Farm Animal Feces with Participation of Citizen Scientists

This paper presents the findings of a large-scale study on antibiotic resistance in bacteria found in farm animal feces across Russia. The study included 6578 samples of farm animal manure from 13 regions in Russia, with the help of citizen scientists. Molecular and microbiological methods were used to analyze 1111 samples of E. coli. The microbiological analysis focused on culturing the microorganisms present in the fecal samples on selective media for E. coli and evaluating the sensitivity of the bacteria to different antibiotics, including ampicillin, tetracycline, chloramphenicol, cefotaxime, and ciprofloxacin. The molecular analysis involved isolating the genomic DNA of the bacteria and conducting PCR assays to detect the vanA, vanB, and mcr-1 antibiotic resistance genes. The results demonstrated significant differences in antibiotic sensitivity of the samples that are morphologically identical to E. coli from different regions. For example, 98.0% and 82.5% of E. coli and other fecal bacterial isolates from the Omsk and Vologda regions lacked antibiotic resistance genes, while 97.7% of samples from the Voronezh region possessed three resistance genes simultaneously. The phenotypic antibiotic sensitivity test also revealed regional differences. For instance, 98.1% of fecal bacterial samples from cattle in the Udmurt Republic were sensitive to all five antibiotics tested, whereas 92.8% of samples from the Voronezh region showed resistance to all five antibiotics. The high level of antibiotic resistance observed may be attributed to their use in farming practices. The distinctive feature of our research is that comprehensive geographical coverage was achieved by using a citizen science platform. Citizen scientists, specifically students from colleges and universities, were responsible for the collection and initial analysis of samples. The project attracted 3096 student participants, enabling the collection and analysis of a significant number of samples from various locations in Russia.

Detection of drug resistance in Escherichia coli from calves with diarrhea in the Tongliao region: an analysis of multidrug-resistant strains

IntroductionEscherichia coli is a major pathogen responsible for calf diarrhea, which has been exacerbated by the irrational and unscientific use of antimicrobial drugs, leading to significant drug resistance.MethodsThis study focused on the isolation and identification of E. coli from calf diarrhea samples in the Tongliao area of China. Isolation was conducted using selective media, Gram staining, and 16S rRNA sequencing. The minimum inhibitory concentration (MIC) of E. coli was determined through the microbroth dilution method. Additionally, the presence of antibiotic-resistant genes was detected, and multidrug-resistant strains were selected for whole-genome sequencing (WGS).ResultsThe results revealed that all 40 isolated strains of E. coli exhibited resistance to sulfadiazine sodium, enrofloxacin, and ciprofloxacin, with 90% of the strains being susceptible to polymyxin B. Notably, strains 11, 23, and 24 demonstrated severe resistance. The detection rates of the antibiotic resistance genes TEM-1, TEM-206, strA, strB, qacH, and blaCTX were 100%, indicating a high prevalence of these genes. Moreover, the majority of strains carried antibiotic resistance genes consistent with their resistance phenotypes. WGS of strains 11, 23, and 24 revealed genome sizes of 4,897,185 bp, 4,920,234 bp, and 4,912,320 bp, respectively. These strains carried two, one, and two plasmids, respectively. The prediction of antibiotic resistance genes showed a substantial number of these genes within the genomes, with strain 24 harboring the highest number, totaling 77 subspecies containing 88 antibiotic resistance genes.DiscussionIn conclusion, all 40 isolated strains of E. coli from calf diarrhea in this study were multidrug-resistant, exhibiting a broad distribution of antibiotic resistance genes and mobile components. This poses a significant risk of horizontal gene transfer, highlighting the critical situation of antibiotic resistance in this region.

Assessment of Antibiotic Resistance in Groundwater Bacterial Strains: A Community-based Study

Background: The microbial quality of private and community water supply from groundwater is mostly not monitored nor assessed by any established government agencies in Nigeria. Contamination by pathogenic and antimicrobial resistant microbial agent, and the potential of resistant genes transfer from environmental bacteria to human pathogens is a major risk for public health in these water systems. Aim: This study was aimed at evaluating the microbiological quality and safety in terms of antibiotic resistance bacterial profile of groundwater sources in a typical peri-urban settlement in Nigeria. Methodology: Bacterial contaminants were isolated by membrane filtration technique, characterized and analyzed using standard microbiological approach. Results: A total of 22 and 8 Gram negative and positive bacteria respectively were isolated. The isolates comprised 7 bacterial genera with Klebsiella and Enterobacter species having the highest incidence of 20% respectively, followed by Bacillus (17%) and least being Shigella with 7% incidence. All the isolates were 100% resistant to cefotaxime, followed by 76.7% and 73.3% resistant to vancomycin and meropenem respectively. The least resistance of 3.3% was against ciprofloxacin. Resistance in borehole storage tank water was highest (80%) against vancomycin followed by 70% for meropenem, while 75% resistance was against vancomycin and meropenem respectively in the well water, Seventy-three percent (73%) of the isolates showed multidrug resistance (MDR) pattern, and a multiple antibiotic resistant index (MARI) ≥ 0.3. Conclusion: The results of this study suggest that groundwater source in the studied community is contaminated with antibiotic resistant bacteria and underscores the public health implication and concern for monitoring of groundwater supply in Nigerian communities.

Systematic screening of 42 vancomycin-resistant Enterococcus faecium strains for resistance, biofilm, and desiccation in simulated microgravity

AbstractVancomycin-resistant Enterococcus faecium (VRE) presents significant challenges in healthcare, particularly for hospitalized and immunocompromised patients, including astronauts with dysregulated immune function. We investigated 42 clinical E. faecium isolates in simulated microgravity (sim. µg) using a 2-D Clinostat, with standard gravity conditions (1 g) as a control. Isolates were tested against 22 antibiotics and characterized for biofilm formation and desiccation tolerance. Results showed varied responses in minimum inhibitory concentration (MIC) values for seven antibiotics after sim. µg exposure. Additionally, 55% of isolates showed a trend of increased biofilm production, and 59% improved desiccation tolerance. This investigation provides initial insights into E. faecium’s changes in response to simulated spaceflight, revealing shifts in antibiotic resistance, biofilm formation, and desiccation tolerance. The observed adaptability emphasizes the need to further understand VRE’s resilience to microgravity, which is crucial for preventing infections and ensuring crew health on future long-duration space missions.

A mixed method approach to analysing patterns and drivers of antibiotic use and resistance in beef farms in Argentina

IntroductionAntimicrobial resistance is a challenge to be faced by all livestock sectors; within beef farming, antibiotic use patterns vary by country and management practices. Argentina is a country with high beef production & consumption but limited information surrounding antibiotic use. The aims of this project was to understand how antibiotics are being used across the beef industry in Argentina and exploring drivers of usage.MethodsQuantitative and qualitative data was collected by: A survey of breeding and feedlot farms including antibiotic use (from purchase data); a detailed analysis of two feedlot farms’ therapeutic antibiotic use records; a survey of vets’ views on certain antibiotic practices; and a focus group of farmers and vets focusing on wider influences affecting decision making. Antibiotic use data was calculated using mg/population corrected unit (PCU) (ESVAC) and thematic analysis was used to identify drivers of antibiotic use among participants.ResultsThe median use across 17 farms that supplied purchase data was 76.52 mg/kg PCU (ESVAC; IQR = 36.81 mg/kg PCU [ESVAC]). The detailed farm records showed that the largest reason for treatment was group treatments (72.92% of treatments) followed by treatment for respiratory disease (12.75% of treatments). Macrolides accounted for 76.37% of treatments. Nearly half of farms used routine prophylactic treatment for arriving animals (n = 7/18). The use of quarantine and ‘sick pens’ were seen as important by surveyed vets with antibiotic prophylaxis and in-feed antibiotics seen as contributors to antibiotic resistance. The focus group highlighted the influence of the economic and political landscape on husbandry practices and the responsibility the farming sector had towards antibiotic stewardship.DiscussionOverall, Argentine beef feedlots resemble North American beef feedlots in terms of antibiotic practices but with considerably lower usage, with in-feed monensin representing a large proportion of total ABU. The adaptation period presents a challenge to animal health; antibiotics are administered a prophylaxis, metaphylactic and individual treatments depending on farm management practices. Further research into internationally comparable measures of ABU and detailed cost-benefit analysis of practical, on-farm interventions are needed to aid improved antimicrobial stewardship in livestock systems globally.

Navigating antibiotic therapy in acute cholangitis: Best practices and new insights

AbstractGlobally, antibiotic resistance is linked to increased morbidity, mortality, and healthcare costs, which necessitates further research on optimal antibiotic usage. Acute cholangitis (AC), a common cause of community‐acquired bacteremia, often requires antimicrobial therapy. Therefore, studying the appropriate use of antibiotics for AC is considered crucial for suppressing the emergence of resistant bacteria and reducing adverse antibiotic‐associated events. The Tokyo Guidelines 2018 (TG18) recommend 4–7 days of antibiotics post‐biliary drainage. However, this lacks strong evidence and is based primarily on various evidence and expert opinions. Recent retrospective studies advocate for a shorter 1–3‐day antibiotic course for AC, thereby prompting a need to reassess the treatment duration to balance therapeutic efficacy and minimize resistance and adverse effects. Choosing the appropriate duration and antibiotics based on susceptibility to pathogens causing cholangitis is important. Awareness of local resistance patterns and understanding patients' risks of resistant pathogens are prerequisite for effective treatment. We must explore the applicability of these guidelines in specific scenarios such as severe AC, positive blood cultures, fever, or hilar biliary obstructions due to malignancy. This comprehensive review considers both the duration and type of antibiotics and aims to enhance treatment outcomes while reducing the risk of resistant bacterial infections.

Emerging Long-Term Risks of the Use of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers

Acid-related disorders represent a significant global health burden. Pharmacological treatment of these conditions has at times been challenged and limited by incomplete effectiveness, antibiotic resistance, adverse medication effects and/or interactions, and disease recurrence. Since the early 1990s, the mainstay of treatment has been proton pump inhibitors (PPIs). Recently, the US Food and Drug Administration issued a clearance for vonoprazan, a potassium-competitive acid blocker (PCAB). PCABs are a new class of acid-suppressing agents that may overcome some of these challenges. The aim of this review is to evaluate and compare the emerging long-term risks of PPI and PCAB therapies.

Impact of Sublethal Disinfectant Exposure on Antibiotic Resistance Patterns of Pseudomonas aeruginosa

Objective: The problem of hospital cross-infection due to contamination of disinfectants has been recognized elsewhere. The passage of bacteria through diluted disinfectants may not only bring about phenotypic changes in their antibiograms but also changes in phage susceptibility patterns. Contact with disinfectants in sublethal concentrations allows survival and multiplication of bacteria. Methods and Materials: Serial passage, through disinfectants at subminimal inhibitory concentrations, induced antibiotic resistance in 18% of derived phenotypic variants of fifty strains of Pseudomonas aeruginosa which were isolated from diarrheal stools of infants in children's hospital. Results: A proportion of these strains became susceptible to an increased number of antibiotics. The present study revealed that all the isolates were resistant to tetracycline and carbenicillin and 40% of these isolates became sensitive to both antibiotics after exposure to disinfectants. The exposure to disinfectants induced neomycin resistance among two isolates. The resistance patterns were three before disinfectants exposure which increased to be nine different patterns after exposure. No antibiotic resistance was transferred between P. aeruginosa and Escherichia coli K12 as a recipient strain. Conclusions: Almost 50% of the isolates tested became sensitive to tetracycline, carbenicillin and co-trimoxazole after exposure to disinfectants. The resistance patterns among the 50 isolates were three which changed to be nine different patterns after exposure to disinfectants. Unjustifiable use of disinfectants might give a chance for survival and multiplication of pathogenic bacteria to develop new resistance patterns to antibiotics in use with a short time. These new resistance variants of bacteria which multiply in hospital environment could lead to serious epidemic conflicts particularly the epidemiological reporting and management.

Targeted Sonodynamic Therapy Platform for Holistic Integrative Helicobacter pylori Therapy

AbstractHelicobacter pylori (H. pylori) is a primary pathogen associated with gastrointestinal diseases, including gastric cancer. The increase in resistance to antibiotics, along with the adverse effects caused by complicated medication protocols, has made the eradication of H. pylori a more formidable challenge, necessitating alternative therapeutics. Herein, a targeted nanoplatform is reported based on sonodynamic therapy, the chitosan‐conjugated fucose loaded with indocyanine green (ICG@FCS). It penetrates the gastric mucosa and homes in on H. pylori through dual targeting mechanisms: molecular via fucose and physical via ultrasound. Upon ultrasound activation, it generates singlet oxygen, effectively attacking planktonic bacteria, disrupting biofilms, and facilitating the clearance of intracellular bacteria by promoting autophagy, including multidrug‐resistant strains. The ICG@FCS nanoplatform minimally affects the gut microbiota and aids in gastric mucosa repair. a holistic integrative H. pylori therapy strategy is proposed that targets eradication while preserving gastrointestinal health. This strategy emphasizes the importance of maintaining patient health while eradicating the pathogen. This advancement is set to refine the comprehensive antibacterial approach, offering a promising horizon in the ongoing battle against antibiotic resistance and more effective gastric cancer prevention strategies.

Antibiotic efficacy and resistance patterns of urinary tract infection-causing bacteria in dogs and resistome of multidrug-resistant Klebsiella pneumoniae via whole genome sequencing in South Korea

Bacterial urinary tract infections (UTIs) are prevalent in dogs and necessitate antibiotic intervention. However, the emergence of multidrug-resistant (MDR) bacteria poses significant challenges to antibiotic therapy. Although fosfomycin has been demonstrated to achieve and maintain high concentrations in urine, suggesting its potential for treating UTIs in dogs, its efficacy and the resistance profiles of urinary pathogens from canine UTIs remain elusive. Therefore, this study was conducted to investigate the antibiotic susceptibility of bacterial pathogens isolated from companion dogs with UTIs, with a particular focus on their susceptibility and resistance to fosfomycin. A total of 70 isolates from urine samples were analyzed, of which Escherichia coli (n = 18), Proteus mirabilis (n = 9), Klebsiella pneumoniae (n = 5), and Staphylococcus pseudintermedius (n = 5) were predominant. Resistance to erythromycin was most prevalent (94.59%), followed by clindamycin (91.89%) and ampicillin (78.37%), whereas the lowest resistance rate was observed for amikacin (5.40%). Resistance to fosfomycin was observed in 15 out of the 37 predominant isolates (40.54%), including all K. pneumoniae isolates (100%). All isolates, except 4 E. coli strains, were categorized as MDR (33 out of 37; 89.18%). The resistance rates for amoxicillin/clavulanic acid and trimethoprim-sulfamethoxazole, which are common first-line antibiotics for canine UTIs, were 48.64 and 56.75%, respectively. Whole-genome sequencing of K. pneumoniae isolates, which exhibited high resistance to fosfomycin, revealed multiple antibiotic resistance genes, with chromosomal fosA present in all isolates. Among the 27 dogs with recurrent infection included in this study, 2 were administered fosfomycin, resulting in clinical remission, as evidenced by negative urine culture tests. Overall, this study is the first to demonstrate the importance of assessing fosfomycin resistance profile for optimal treatment of canine UTIs, particularly in cases involving MDR strains.

Antibiotic Resistance, and Biofilm Forming Characteristics of Escherichia coli Clinical Isolates at a Hospital in Tigray, Northern Ethiopia

Antibiotic Resistance, and Biofilm Forming Characteristics of Escherichia coli Clinical Isolates at a Hospital in Tigray, Northern Ethiopia

Clinical characteristics associated with peripartum maternal bloodstream infection

ObjectiveBloodstream infection (BSI) during the peripartum period is a major cause of maternal morbidity and mortality. However, data on maternal BSI during hospitalization for delivery are limited. This study aimed to investigate the incidence, clinical characteristics, risk factors, microbiological features, and antibiotic resistance patterns of maternal peripartum BSI, with a focus on understanding the role of premature rupture of membranes (PROM), fever, and other risk factors in its development.MethodsWe investigated the clinical characteristics associated with maternal BSI during the peripartum period. This study included febrile women with blood cultures obtained during hospitalization for delivery. We analyzed the clinical characteristics, pathogenic microorganisms, antibiotic resistance, and maternal and neonatal outcomes of these patients. Participants were divided into BSI (n = 85) and non-BSI (n = 361) groups.ResultsSpontaneous rupture of membranes, PROM, PROM >24 h before labor, vaginal examinations >5 times, and cesarean sections during labor were more common in the BSI group. Escherichia coli (51.8%; 44/85) was the predominant causative pathogen, followed by Enterococcus faecalis (7.1%, 6/85). Approximately 31.2% of E. coli were resistant to levofloxacin, and 38.6% were extended-spectrum β-lactamase-producing bacteria. The BSI group had higher rates of maternal sepsis and Apgar scores ≤ 7 at 1 min than the non-BSI group. Furthermore, PROM, fever ≥38.9°C (102°F), and fever within 24 h after delivery were risk factors for postpartum BSI in the adjusted analysis.ConclusionMaternal BSI is a potentially life-threatening disease associated with PROM and the timing and severity of fever. Early identification and surveillance of pathogen composition and antimicrobial resistance can help prevent adverse outcomes.

Role of VapBC4 toxin-antitoxin system of Sulfolobus acidocaldarius in heat stress adaptation

ABSTRACT Toxin-antitoxin (TA) systems are important for stress adaptation in prokaryotes, including persistence, antibiotic resistance, pathogenicity, and biofilm formation. Toxins can cause cell death, reversible growth stasis, and direct inhibition of crucial cellular processes through various mechanisms, while antitoxins neutralize the effects of toxins. In bacteria, these systems have been studied in detail, whereas their function in archaea remains elusive. During heat stress, the thermoacidophilic archaeon Sulfolobus acidocaldarius exhibited an increase in the expression of several bicistronic type II vapBC TA systems, with the highest expression observed in the vapBC4 system. In the current study, we performed a comprehensive biochemical characterization of the VapBC4 TA system, establishing it as a bonafide type II toxin-antitoxin system. The VapC4 toxin is shown to have high-temperature catalyzed RNase activity specific for mRNA and rRNA, while the VapB4 antitoxin inhibits the toxic activity of VapC4 by interacting with it. VapC4 toxin expression led to heat-induced persister-like cell formation, allowing the cell to cope with the stress. Furthermore, this study explored the impact of vapBC4 deletion on biofilm formation, whereby deletion of vapC4 led to increased biofilm formation, suggesting its role in regulating biofilm formation. Thus, during heat stress, the liberated VapC4 toxin in cells could potentially signal a preference for persister cell formation over biofilm growth. Thus, our findings shed light on the diverse roles of the VapC4 toxin in inhibiting translation, inducing persister cell formation, and regulating biofilm formation in S. acidocaldarius , enhancing our understanding of TA systems in archaea. IMPORTANCE This research enhances our knowledge of toxin-antitoxin (TA) systems in archaea, specifically in the thermoacidophilic archaeon Sulfolobus acidocaldarius . TA systems are widespread in both bacterial and archaeal genomes, indicating their evolutionary importance. However, their exact functions in archaeal cellular physiology are still not well understood. This study sheds light on the complex roles of TA systems and their critical involvement in archaeal stress adaptation, including persistence and biofilm formation. By focusing on S. acidocaldarius , which lives in habitats with fluctuating temperatures that can reach up to 90°C, the study reveals the unique challenges and survival mechanisms of this organism. The detailed biochemical analysis of the VapBC4 TA system, and its crucial role during heat stress, provides insights into how extremophiles can survive in harsh conditions. The findings of this study show the various functions of the VapC4 toxin, including inhibiting translation, inducing persister-like cell formation, and regulating biofilm formation. This knowledge improves our understanding of TA systems in thermoacidophiles and has broader implications for understanding how microorganisms adapt to extreme environments.

Tackling antibiotic resistance—insights from eHealthResp’s educational interventions

Tackling antibiotic resistance—insights from eHealthResp’s educational interventions

Hops bitter β‐acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction

AbstractBackgroundRoutine 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.MethodsHuman 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.ResultsWe 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.ConclusionOur 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.

Gut Microbiome Characterisation of Chrysomya megacephala: Isolation, Identification, Antibiotic Profiling, and Initial Documentation of Leclercia adecarboxylata from the Fly

Chrysomya megacephala, known for its vector potential, harbors a diverse microbiota crucial in understanding disease transmission dynamics. Herein, we report the first documentation of Leclercia adecarboxylata isolated from C. megacephala. L. adecarboxylata is an Enterobacteriaceae, gram-negative bacillus that cause infections in human and animals. Additionally, we have reported the presence of Pseudomonas aeruginosa and Enterococcus faecalis from C. megacepahala. The study carried out the antibiotic profiling and hemolytic assays, which revealed distinct resistance patterns and virulence characteristics, shedding light on potential public health implications. L. adecarboxylata, Pseudomonas aeruginosa and Enterococcus faecalis showed positive result for hemolysis and in terms of antibiotic resistance P. aeruginosa strains showed resistance to Amoxicillin, Ampicillin and Tetracycline while, E. faecalis showed resistance towards Streptomycin and Tetracycline. However, L. adecarboxylata showed sensitivity to all antibiotics. This study was conducted from Kozhikode, Kerala, India, and this is the first of its kind of study from the region to analyse the vector potential of C. megacephala. These findings underscore the significance of comprehensive microbiological investigations in vector-borne disease surveillance and management strategies.