Antimicrobial Agents and Chemotherapy最新文献

{"title":"Harnessing the effect of iron deprivation to attenuate the growth of opportunistic pathogen <i>Acinetobacter baumannii</i>.","authors":"Sujata Saha, Debasrita RoyChowdhury, Ali Hossain Khan, Sukhendu Mandal, Kunal Sikder, Dipak Manna, Amit Ranjan Maity, Soumyananda Chakraborti, Arnab Basu","doi":"10.1128/aac.01689-24","DOIUrl":"https://doi.org/10.1128/aac.01689-24","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is an opportunistic pathogen having high infectivity among immunocompromised patients. The bacteria are resistant to major first-line antibiotics and have become a serious concern in the aspect of nosocomial and community-acquired infections. To overcome this dire situation, the necessity of introducing new approaches is undeniable, which can bypass the need for conventional antibiotic therapy. In this article, we have pinpointed the importance of iron in <i>A. baumannii.</i> Iron is an essential micronutrient in all bacteria. Loss of iron acquisition leads to membrane destabilization, and change in the expression of iron-transporting or -metabolizing genes causes death of the bacteria. Iron scavenging was primarily mediated by different chelators, and β-thujaplicin showed the best antibacterial efficacy with respect to time killing assay and CFU analysis. When iron (Fe<i>²⁺</i>) was supplemented after initial deficiency, the growth of the bacteria was seen to be restored. Iron deprivation also disintegrates the biofilm matrix, a major cause of bacterial resistance against different types of antibiotics. Moreover, iron scavenging promotes inhibition of biofilm sessile persister cells, the root cause of recalcitrant and chronic infection. As a part of antimicrobial therapy, β-thujaplicin was treated alongside colistin and chloramphenicol at an amount significantly lower than its MIC value. Our results indicated that β-thujaplicin nicely complemented those antibiotics to potentiate their antimicrobial action. In a nutshell, iron chelating agents are potential alternative therapeutics that can be used alongside different antibiotics to circumvent the resistance of different nosocomial pathogens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0168924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of copper chelators on the budding in <i>Candida albicans</i>.","authors":"Yushi Futamura, Kai Yamamoto, Rachael Uson-Lopez, Harumi Aono, Takeshi Shimizu, Yasuhiro Hori, Kuniki Kino, Hiroyuki Osada","doi":"10.1128/aac.00033-25","DOIUrl":"https://doi.org/10.1128/aac.00033-25","url":null,"abstract":"<p><p><i>Candida albicans</i> exhibits a unique dimorphic behavior, allowing it to switch between unicellular budding yeast and filamentous hyphal growth. This dimorphism is crucial for its pathogenicity, influencing processes such as adhesion, invasion, immune evasion, and host response. A comprehensive understanding of the molecular mechanisms governing yeast and hyphal growth, as well as the switch between these forms, is crucial for the development of effective anticandidal therapies. In this study, we screened for small molecules that interfere with the dimorphism of <i>C. albicans</i> and identified the actinomycete metabolite RK-276A/SF2768 as a potent inhibitor of this process. Time-lapse microscopy revealed that SF2768 inhibited hyphal branching and lateral yeast budding during the hyphal-to-yeast transition. Interestingly, SF2768 also suppressed farnesol-induced yeast growth by inhibiting yeast bud formation. The effects of SF2768 were canceled with copper addition, and other copper chelators, such as trientine and d-penicillamine, induced similar phenotypes, indicating that the copper-chelating activity of SF2768 is crucial for its antifungal properties. Furthermore, copper ions induced both hyphal and yeast bud formation. These findings strongly suggest that copper ions play a role in <i>Candida</i> budding, and the copper chelators could be developed as novel antifungal agents against not only dimorphic <i>Candida</i> spp. but also non-dimorphic <i>Candida</i> spp.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0003325"},"PeriodicalIF":4.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and genotypic resistance to bedaquiline in patients with multi-drug-resistant tuberculosis-experiences from Armenia.","authors":"E Ardizzoni, W Mulders, M De Diego Fuertes, A Hayrapetyan, A Mirzoyan, J Faqirzai, N Khachatryan, I Oganezova, F Varaine, M Bastard, P Graulus, C J Meehan, L Rigouts, B C de Jong, T Decroo, C Hewison, A Van Rie","doi":"10.1128/aac.01839-24","DOIUrl":"https://doi.org/10.1128/aac.01839-24","url":null,"abstract":"<p><p>Risk factors for baseline bedaquiline (BDQ) resistance, amplification during treatment, and correlations with treatment outcomes are not fully understood. This cohort included Armenian patients with multidrug-resistant TB predominantly fluoroquinolone-resistant enrolled between 2013 and 2015 in a BDQ compassionate use program. BDQ resistance at baseline and during treatment was assessed using MGIT (pDST_MGIT), minimal inhibitory concentration in 7H11 (MIC_7H11), and whole-genome sequencing. Risk factors, such as treatment effectiveness or stage of the disease, were analyzed for association with baseline BDQ resistance, acquired BDQ resistance, and treatment outcome. Among 39 patients, baseline BDQ resistance was 6% (2/33) by pDST_MGIT and 7% (2/29) by MIC_7H11. All four baseline isolates with an <i>Rv0678</i> mutation were phenotypically resistant. During treatment, 48% of the patients acquired BDQ resistance by pDST_MGIT, and 52% acquired mutations at various frequencies (97% in <i>Rv0678</i>). None of the factors significantly contributed to baseline or acquired BDQ resistance. Unfavorable treatment outcome (41%) was more frequent in the presence of acquired <i>Rv0678</i> mutations [odds ratio (OR) 132, 95% confidence interval (CI) 7.43, 2375], phenotypic BDQ resistance (OR 176, 95% CI 6.48, 2423), or MIC increase above or below the critical concentration (both OR 84.3, 95% CI 2.93, 2423) during treatment. For these highly treatment-experienced patients, low baseline prevalence but high incidence of acquired BDQ resistance was observed. Acquisition of mutations in BDQ candidate resistance genes, regardless of their frequency, or increased MICs during treatment, even below the critical concentration, should be seen as a warning sign of resistance amplification and increased risk of unfavorable treatment outcome.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0183924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of a novel major facilitator superfamily (MFS) efflux pump conferring multidrug resistance in <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>.","authors":"Honghao Huang, Yiyi Chen, Lingxuan Zhang, Peng Wan, Yan Chen, Yafei Li, Zhenling Zeng","doi":"10.1128/aac.01739-24","DOIUrl":"https://doi.org/10.1128/aac.01739-24","url":null,"abstract":"<p><p>A novel major facilitator superfamily (MFS) efflux pump in <i>Staphylococcus</i>, designated Nms, was identified via topology prediction. The secondary structure indicated the presence of 12 transmembrane segments (TMSs) and characteristic motif A of MFS efflux pumps. Experimental verification of efflux activity was conducted using ethidium bromide accumulation and efflux assays and biofilm formation assays. Antimicrobial susceptibility testing and efflux pump inhibition confirmed that Nms effectively effluxed various antimicrobial agents to confer multidrug resistance. Comprehensive genomic analyses were used to assess the prevalence and possible origins of the <i>nms</i> gene. The results revealed that the <i>nms</i> gene was present in <i>Staphylococcus aureus</i> ST398/ST541 and <i>Staphylococcus epidermidis</i> ST570/ST1166 strains from global isolates. The transmission of <i>nms</i> was associated with the prevalence of <i>S. aureus</i> ST398-t571 in swine-derived samples from China. Phylogenetic analysis revealed that <i>nms-</i>positive strains formed a distinct clade separate from other <i>S. aureus</i> ST398 strains. Genetic analysis of the <i>nms</i> gene revealed a significant presence of plasmid-related mobile genetic elements, with extended nucleotide sequences containing circular intermediates exhibiting high homology with those found in an <i>S. aureus</i> plasmid. These findings suggested that the <i>nms</i> gene likely initially originated from plasmids and subsequently integrated into chromosomes. In conclusion, Nms is a novel MFS efflux pump that confers multidrug resistance to <i>S. aureus</i> and has been carried predominantly by ST398-t571 isolates in recent years. Ongoing surveillance is essential to elucidate the origin of <i>nms</i> in <i>S. aureus</i>, particularly MRSA ST398-t571, and to understand the transmission among humans, animals, and the environment.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0173924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation, structure, and activity of the <i>Pseudomonas aeruginosa</i> MexXY efflux system.","authors":"Logan G Kavanaugh, Megan E Hinrichsen, Christine M Dunham, Graeme L Conn","doi":"10.1128/aac.01825-24","DOIUrl":"https://doi.org/10.1128/aac.01825-24","url":null,"abstract":"<p><p>The current crisis in bacterial antibiotic resistance can be attributed to the overuse (or misuse) of these essential medicines in healthcare and agriculture, coupled with the slowed progression of new drug development. In the versatile, opportunistic pathogen <i>Pseudomonas aeruginosa</i>, the Resistance-Nodulation-Division (RND) efflux pump MexXY plays critical roles in both cell physiology and the acquisition of multidrug resistance. The <i>mexXY</i> operon is not constitutively expressed, but this process is instead controlled by a complex network of multiple interconnected regulatory mechanisms. These include induction by several of the pump's ribosome-targeting antibiotic substrates and transcriptional repression and anti-repression processes that are themselves influenced by various cellular factors, processes, or stresses. Although extensive studies of the MexXY complex are currently lacking as compared to other RND efflux pumps such as <i>Escherichia coli</i> AcrAB-TolC, recent studies have provided valuable insights into the MexXY architecture and substrate profiles, including its contribution to clinical resistance. Furthermore, while MexXY primarily associates with the outer membrane protein OprM, emerging evidence suggests that this transporter-periplasmic adaptor pair may also partner with other outer membrane proteins, potentially to alter the efflux substrate profile and activity under specific environmental conditions. In this minireview, we summarize current understanding of MexXY regulation, structure, and substrate selectivity within the context of clinical resistance and as a framework for future efflux pump inhibitor development.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0182524"},"PeriodicalIF":4.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of novel ceftibuten-avibactam, ceftazidime-avibactam, and comparators against a challenge set of <i>Enterobacterales</i> from outpatient centers and nursing homes across the United States (2022-2024).","authors":"Aliaa Fouad, April M Bobenchik, Robin Chamberland, Andrew E Clark, Holly K Huse, Isabella W Martin, A Brian Mochon, Erik Munson, Maroun M Sfeir, Monica Srodon, Kimberly Taylor, Yungchou Wang, Lars F Westblade, David P Nicolau, Tomefa E Asempa","doi":"10.1128/aac.01867-24","DOIUrl":"https://doi.org/10.1128/aac.01867-24","url":null,"abstract":"<p><p>Ceftibuten is being developed in combination with the oral prodrug of avibactam. Outpatient isolates (<i>n</i> = 500) from 11 US states underwent susceptibility testing with manual broth microdilution. Ceftibuten had susceptibility rates of 64% (CLSI) and 23% (EUCAST). Ceftibuten-avibactam achieved 96.4% inhibition at MIC ≤ 1 µg/mL. Susceptibility rates were as follows: cefpodoxime (2.6%), ceftriaxone (1%), ceftazidime-avibactam (99.6%), tebipenem (89%), ertapenem (94.4%), levofloxacin (26.6%), trimethoprim-sulfamethoxazole (40.2%), and fosfomycin (96.8%). Ceftibuten-avibactam demonstrates potent <i>in vitro</i> activity against cephalosporin non-susceptible isolates.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0186724"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A small regulatory RNA controls antibiotic adaptation in <i>Staphylococcus aureus</i> by modulating efflux pump expression.","authors":"Kam Pou Ha, Etornam Kofi Kumeko, Philippe Bouloc","doi":"10.1128/aac.01176-24","DOIUrl":"https://doi.org/10.1128/aac.01176-24","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is an opportunistic pathogen that poses a considerable burden to healthcare settings worldwide, aided by its ability to thrive in different environmental growth conditions and survive exposure to antibiotics. Small regulatory RNAs (sRNAs) are decisive in enhancing bacterial fitness by modulating gene expression in response to changing environmental conditions. We investigated the role of sRNAs in the adaptation of <i>S. aureus</i> to antibiotics. By assessing the fitness of a library of sRNA mutants, we identified that RsaA sRNA is required for optimal bacterial growth when exposed to low concentrations of fluoroquinolone, a class of antibiotics targeting DNA replication. We also found that in the absence of RsaA, <i>S. aureus</i> is less susceptible to β-lactam antibiotics, which act on the cell wall. RsaA has been reported to prevent the expression of MgrA, a master regulatory protein controlling the expression of efflux pumps. Here, we show that RsaA affects the sensitivity of <i>S. aureus</i> to fluoroquinolone and β-lactam antibiotics through MgrA. RsaA has two forms, a short one commonly referred to in RsaA studies, and a long form about twice the length, of which less is known. Interestingly, our phenotype was only restored when complemented with the long form of the gene or when it was supplied in two parts, the short form and the missing part to obtain the long form. This work demonstrates the role of regulatory RNAs in the adaptation of <i>S. aureus</i> to antibiotic resistance and highlights their value as potential therapeutic targets for manipulating individual sRNA responses to promote the efficacy of existing antibiotics.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0117624"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of phenotypic and genotypic methods for detecting KPC variants.","authors":"Yasmine Benhadid-Brahmi, Claire Amaris Hobson, Lydia Abdelmoumene, Ella Jaouen, Mélanie Magnan, Maud Gits-Muselli, Mathilde Lescat, Olivier Tenaillon, Stéphane Bonacorsi, André Birgy","doi":"10.1128/aac.00082-25","DOIUrl":"https://doi.org/10.1128/aac.00082-25","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> carbapenemases (KPCs) have spread and diversified extensively. To date, 242 clinical variants have been identified and harbor different hydrolytic capacities, thereby interfering with rapid diagnostic tests. The accurate detection of KPC variants is crucial to guide treatment and control measures in healthcare settings. We constructed KPC variants to assess the mutational impact on detection capacities of resistance-based tests. KPC variants (<i>n</i> = 45) were characterized phenotypically and used to measure the detection sensitivity of KPC detection methods (two lateral flow immunoassays [LFIAs], three hydrolysis tests, three selective culture media, and two PCR-based tests). We identified four antibiotic susceptibility patterns: \"KPC-like\" (23/45; 51%), \"extended-spectrum beta-lactamase-like\" (6/45; 13%), \"ceftazidimase\" (9/45; 20%), and outlier variants with \"mixed-profiles\" (5/45; 11%). These phenotypes had different impacts on the detection capabilities of hydrolysis tests (0%-100%), LFIA (44%-100%), and selective culture media (0%-100%), highlighting a risk of misdiagnosis for some KPC variants. All variants were detected with PCR-based tests. To detect the maximum of KPC variants, fecal carriage screening requires a combination of selective media targeting resistance to carbapenems, third-generation cephalosporins, and ceftazidime-avibactam. From antibiotic susceptibility testing, resistance to ceftazidime ± avibactam and specific phenotypic profiles should be used as warnings to track the presence of KPC variants. We recommend LFIA as a first-line test, owing to its high sensitivity in detecting KPC variants. Nevertheless, using a combination of tests may remain wise in some situations. The spread of KPC variants remains a significant concern, particularly as reversion to ancestral phenotype could restore carbapenem resistance and lead to therapeutic failure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0008225"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The newly identified <i>grdA</i> gene confers high-level plazomicin resistance in <i>Salmonella enterica</i> serovars.","authors":"Ahmed F Hikal, Shaohua Zhao, Steven Foley, Ashraf A Khan","doi":"10.1128/aac.01606-24","DOIUrl":"https://doi.org/10.1128/aac.01606-24","url":null,"abstract":"<p><p>Plazomicin, a next-generation aminoglycoside, was recently approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant complicated urinary tract infections. It is highly effective against most aminoglycoside-modifying enzymes (AMEs). Here, we report that <i>Salmonella enterica</i> strains containing the newly identified gentamicin resistance gene (<i>grdA</i>) are highly resistant to plazomicin. Heterologous expression of <i>grdA</i> in <i>Escherichia coli</i> Δ<i>tolC</i> resulted in plazomicin resistance with minimum inhibitory concentration (MIC) > 256 µg/mL. These findings reveal that GrdA confers significantly higher resistance to plazomicin than the previously known plazomicin-resistant AMEs AA (2)-Ia and APH (2″)-Iva.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0160624"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antimycotic 5-fluorocytosine is a virulence inhibitor of uropathogenic <i>Escherichia coli</i> and eradicates biofilm-embedded bacteria synergizing with β-lactams.","authors":"Srikanth Ravishankar, Antonietta Lucia Conte, Stacy Julisa Carrasco Aliaga, Valerio Baldelli, Karen Leth Nielsen, Moira Paroni, Maria Pia Conte, Paolo Landini, Elio Rossi","doi":"10.1128/aac.00280-25","DOIUrl":"https://doi.org/10.1128/aac.00280-25","url":null,"abstract":"<p><p>Biofilm can enhance antibiotic tolerance in bacteria, making treatment of biofilm-associated infections in clinical settings a significant challenge. 5-Fluorocytosine (5-FC), an FDA-approved drug mostly used as an antifungal, can hinder biofilm formation and production of virulence factors in Gram-negative bacteria. In this study, we tested 5-FC on nine uropathogenic <i>Escherichia coli</i> (UPEC) strains plus a fecal isolate. Our data indicated that 5-FC reduced curli fiber gene expression and inhibited virulence factors in UPEC strains. Unlike what was observed in other microorganisms, 5-FC antivirulence and antibiofilm properties were unaffected by either growth temperature or the medium pH, which might prove critical in urinary tract infection (UTI) treatment. Additionally, 5-FC impaired the expression of various UPEC virulence factors, including secreted toxins and type I and P fimbriae, thus leading to decreased UPEC adherence to bladder epithelial cells and improved survival of host cells. Finally, we found that a combination of 5-FC with β-lactams, but not other classes of antibiotics, significantly lowered the viability of bacteria in preformed biofilms. Despite a small set of pathogenic <i>E. coli</i> strains and an <i>in vitro</i> infection model, our findings strongly suggest that 5-FC might be a possible candidate as an antivirulence agent, particularly in a synergistic approach with β-lactam antibiotics.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0028025"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}