Mei-Juan Yang , Meng-Jie Li , Li-Dan Huang , Xin-Wei Zhang , Yan-Ying Huang , Xiao-Yu Gou , Sui-Ning Chen , Jie Yan , Peng Du , Ai-Hua Sun
{"title":"Response regulator protein CiaR regulates the transcription of ccn-microRNAs and β-lactam antibiotic resistance conversion of Streptococcus pneumoniae","authors":"Mei-Juan Yang , Meng-Jie Li , Li-Dan Huang , Xin-Wei Zhang , Yan-Ying Huang , Xiao-Yu Gou , Sui-Ning Chen , Jie Yan , Peng Du , Ai-Hua Sun","doi":"10.1016/j.ijantimicag.2024.107387","DOIUrl":"10.1016/j.ijantimicag.2024.107387","url":null,"abstract":"<div><h3>Background</h3><div><em>Streptococcus pneumoniae</em> does not produce β-lactamases, and its reduced susceptibility to β-lactam antibiotics is predominantly caused by mutations of penicillin-binding proteins (PBPs). However, mechanisms of non–PBP mutation–related β-lactam antibiotic resistance in pneumococcal strains remain poorly characterized.</div></div><div><h3>Methods</h3><div>Susceptibility of <em>S. pneumoniae</em> ATCC49619 and its <em>ciaR</em> gene knockout, complemented, or overexpression mutant (Δ<em>ciaR</em>, CΔ<em>ciaR</em>, or <em>ciaR<sup>OE</sup></em>) to penicillin, cefotaxime, and imipenem was detected using an E-test. Levels of pneumococcal <em>ciaR</em>-mRNA, 5 ccn-microRNAs, and 6 <em>pbps</em>-mRNAs were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Recombinant CiaR (rCiaR) binding to the promoters of ccn-microRNA genes was confirmed using electrophoresis mobility shift and chromatin immunoprecipitation assays. Sequence matching between the ccn-microRNAs and <em>pbps</em>-mRNAs was analyzed using IntaRNA software.</div></div><div><h3>Results</h3><div><em>S. pneumoniae</em> ATCC49619 was sensitive to the 3 β-lactam antibiotics, but overexpression of CiaR, a response regulator protein in 2-component system, caused the increase of MICs against these antibiotics. The <em>ciaR<sup>OE</sup></em> mutant exhibited the significantly increased transcription of ccn-microRNAs but notably decreased transcription of <em>pbps</em>-mRNAs; conversely, the Δ<em>ciaR</em> mutant displayed decreased levels of ccn-microRNAs and increasesed transcription of <em>pbps</em>-mRNAs. rCiaR was able to bind to the promoters of all ccn-microRNA genes <em>in vitro</em> and within cells. The 3 antibiotics at 1/8 minimal inhibitory concentrations caused a significant increase in the <em>ciaR</em>-mRNA and ccn-microRNAs. The mRNA-binding seed sequences in the 5 ccn-microRNAs matched all the promoter-containing sequences of <em>pbps</em>-mRNAs.</div></div><div><h3>Conclusions</h3><div>β-Lactam antibiotics at low concentrations induce non–PBP mutation–related antibiotic resistance conversion of <em>S. pneumoniae</em> by decrease of PBPs through the pathway of CiaR-mediated transcriptional increase of ccn-microRNAs and ccn-microRNA-dependent degradation of <em>pbp-</em>mRNAs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107387"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681685","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}
Yongjian Liu , Ran Wang , Lijun Sun , Aixin Li , Zhengyang Li , Qian Kang , Yuxin Feng , Shiyun Lv , Yuanyi Zhai , Rui Li , Wei Hua , Xi Wang , Yue Gao , Zhangli Wang , Yuguang Feng , Jingwan Han , Lei Jia , Xiaolin Wang , Bohan Zhang , Hanping Li , Lili Dai
{"title":"HIV-1 viral decay in blood and semen in antiretroviral-naïve adults initiating dolutegravir/lamivudine vs. bictegravir/emtricitabine/tenofovir alafenamide","authors":"Yongjian Liu , Ran Wang , Lijun Sun , Aixin Li , Zhengyang Li , Qian Kang , Yuxin Feng , Shiyun Lv , Yuanyi Zhai , Rui Li , Wei Hua , Xi Wang , Yue Gao , Zhangli Wang , Yuguang Feng , Jingwan Han , Lei Jia , Xiaolin Wang , Bohan Zhang , Hanping Li , Lili Dai","doi":"10.1016/j.ijantimicag.2024.107396","DOIUrl":"10.1016/j.ijantimicag.2024.107396","url":null,"abstract":"<div><h3>Background</h3><div>Co-formulated dolutegravir and lamivudine (DTG/3TC) is recommended as the first-line antiretroviral therapy (ART); however, the data on the viral decay in seminal plasma (SP) and blood plasma (BP), as well as changes in inflammatory biomarkers in BP, remain limited among antiretroviral-naïve people with HIV (PWH) receiving DTG/3TC. A prospective observational cohort study was conducted to compare the impact of DTG/3TC vs. bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) on viral decay kinetics and changes in inflammatory biomarkers in antiretroviral-naïve PWH.</div></div><div><h3>Methods</h3><div>Newly diagnosed PWH who initiated BIC/FTC/TAF (n=57) or DTG/3TC (n=43) were enrolled. BP and SP were collected at 0, 4, 12, 24, and 48 weeks after ART initiation. The primary endpoint was viral suppression of HIV-1 in BP and SP at week 48. Secondary endpoints included changes in HIV-1 DNA levels and inflammatory biomarkers over the 48-week follow-up.</div></div><div><h3>Results</h3><div>Overall, 96 (96.0%) PWH completed the 48-week follow-up (DTG/3TC, n=40; BIC/FTC/TAF, n=56). Viral suppression rates in BP and SP were comparable in the BIC/FTC/TAF and DTG/3TC groups in the per-protocol analyses at week 48 (BP, 96.4% vs. 100%, <em>P</em>=0.519; SP, 100% vs. 100%, <em>P</em>>0.999). Both regimens demonstrated similar effectiveness in reducing HIV-1 RNA levels in BP (3.0 vs. 3.1 log<sub>10</sub> copies/mL) and SP (0.9 vs. 1.2 log<sub>10</sub> copies/mL). There were no statistically significant differences in the reductions in HIV-1 DNA levels and changes in inflammatory biomarkers over the 48-week follow-up.</div></div><div><h3>Conclusion</h3><div>These findings indicated comparable effectiveness of DTG/3TC vs. BIC/FTC/TAF in achieving viral suppression in BP and SP, and similar changes in inflammatory biomarkers in BP.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107396"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755101","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}
Weiwei Yang , Heping Xu , Yuanxun Zhao , Wannan Chen , Xiaobo Ma , Fupin Hu
{"title":"Identification of blaKPC-90 in Klebsiella pneumoniae associated with ceftazidime-avibactam resistance and the translocation & truncation of resistant genes mediated by IS26","authors":"Weiwei Yang , Heping Xu , Yuanxun Zhao , Wannan Chen , Xiaobo Ma , Fupin Hu","doi":"10.1016/j.ijantimicag.2024.107388","DOIUrl":"10.1016/j.ijantimicag.2024.107388","url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, we discovered <em>bla</em><sub>KPC-90</sub> in ceftazidime-avibactam resistant clinical isolates of <em>K. pneumoniae</em> from a patient with multiple comorbidities and investigated the resistance & transfer mechanism of <em>bla</em><sub>KPC-90</sub>.</div></div><div><h3>Methods</h3><div><em>K. pneumoniae</em> strains carrying <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>KPC-90</sub> were isolated from the patient. Antimicrobial susceptibility tests and whole genome sequencing were performed to investigate the phenotype & genotype of strains. Conjugation assays, cloning experiment, kinetic parameters measuring, outer membrane protein SDS-PAGE and qRT-PCR were performed to explore the spread and antimicrobial resistance mechanisms.</div></div><div><h3>Results</h3><div>KPC-90 isolates had an insertion of two amino acids (Thr180_Ser181 ins Tyr Thr) compared to the wildtype KPC-2. Antimicrobial susceptibility testing of isolates with KPC-90 vs. KPC-2 showed ceftazidime-avibactam MICs of >128 vs. 1–2 mg/L, meropenem-vaborbactam MICs of 4 vs. 1 mg/L, meropenem MICs of 4–8 vs. >128 mg/L and imipenem MICs of 0.5–1 vs. 64 mg/L. Analysis of kinetic parameters of KPC-90 compared to KPC-2 showed decreased hydrolysis of carbapenems and increased IC50 of avibactam. Genetic characterization of the plasmid revealed that IS26 could mediate the intramolecular inversion, translocation and truncation of the resistance determinant region.</div></div><div><h3>Conclusion</h3><div>We have described the case of a patient infected with <em>bla</em><sub>KPC-90</sub>-carrying <em>K. pneumoniae</em> strains and investigated the mechanism of resistance to carbapenems and ceftazidime-avibactam associated with <em>bla</em><sub>KPC-2</sub> and its variants. We have also focused on the functional diversity of IS26 in relation to antimicrobial resistance. In the future, it is crucial to pay more attention to the evolution and horizontal transmission of <em>bla</em><sub>KPC</sub>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107388"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647974","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}
K. M. Taufiqur Rahman , Ruqayyah Amaratunga , Xuan Yi Butzin , Abhyudai Singh , Tahmina Hossain , Nicholas C. Butzin
{"title":"Rethinking dormancy: Antibiotic persisters are metabolically active, non-growing cells","authors":"K. M. Taufiqur Rahman , Ruqayyah Amaratunga , Xuan Yi Butzin , Abhyudai Singh , Tahmina Hossain , Nicholas C. Butzin","doi":"10.1016/j.ijantimicag.2024.107386","DOIUrl":"10.1016/j.ijantimicag.2024.107386","url":null,"abstract":"<div><h3>Objectives</h3><div>Bacterial persisters are a subpopulation of multidrug-tolerant cells capable of surviving and resuming activity after exposure to bactericidal antibiotic concentrations, contributing to relapsing infections and the development of antibiotic resistance. In this study, we challenge the conventional view that persisters are metabolically dormant by providing compelling evidence that an isogenic population of <em>Escherichia coli</em> remains metabolically active in persistence.</div></div><div><h3>Methods</h3><div>Using transcriptomic analysis, we examined E. coli persisters at multiple time points following exposure to bactericidal concentrations of ampicillin (Amp). Some genes were consistently upregulated in Amp treated persisters compared to the untreated controls, a change that can only occur in metabolically active cells capable of increasing RNA levels.</div></div><div><h3>Results</h3><div>Some of the identified genes have been previously linked to persister cells, while others have not been associated with them before. If persister cells were metabolically dormant, gene expression changes over time would be minimal during Amp treatment. However, network analysis revealed major shifts in gene network activity at various time points of antibiotic exposure.</div></div><div><h3>Conclusions</h3><div>These findings reveal that persisters are metabolically active, non-dividing cells, thereby challenging the traditional view that they are dormant.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107386"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anand K. Keshri , Suraj S. Rawat , Anubha Chaudhary , Swati Sharma , Ananya Kapoor , Parul Mehra , Rimanpreet Kaur , Amit Mishra , Amit Prasad
{"title":"LL-37, the master antimicrobial peptide, its multifaceted role from combating infections to cancer immunity","authors":"Anand K. Keshri , Suraj S. Rawat , Anubha Chaudhary , Swati Sharma , Ananya Kapoor , Parul Mehra , Rimanpreet Kaur , Amit Mishra , Amit Prasad","doi":"10.1016/j.ijantimicag.2024.107398","DOIUrl":"10.1016/j.ijantimicag.2024.107398","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) represent a unique group of naturally occurring molecules having diverse biological activities, including potent antimicrobial properties. Among them, LL-37 has emerged as a significant player, demonstrating its multifaceted roles during bacterial, fungal, and viral infections, as well as exhibiting intriguing implications in cancer. This review delves into the versatile functions of LL-37, elucidating its mechanisms of action against microbial pathogens and its potential to modulate immune responses. We explored the efficacy of LL-37 in disrupting bacterial membranes, inhibiting fungal growth, and interfering with viral replication, highlighting its potential as a therapeutic agent against a wide array of infectious diseases. Furthermore, we discussed the emerging role of LL-37 in cancer immunity, where its immunomodulatory effects and direct cytotoxicity towards cancer cells offer novel avenues for cancer therapy in the near future. We provided a comprehensive overview of the activities of LL-37 across various diseases and underscored the importance of further research into harnessing the therapeutic potential of this potential antimicrobial peptide along with other suitable candidates.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107398"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791640","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":"Anakinra efficacy in COVID-19 pneumonia guided by soluble urokinase plasminogen activator receptor: Association with the inflammatory burden of the host","authors":"Evdoxia Kyriazopoulou , Karolina Akinosoglou , Eleni Florou , Elli Kouriannidi , Artemis Bogosian , Olga Tsachouridou , Konstantinos N. Syrigos , Nikolaos Gatselis , Haralampos Milionis , Ilias C. Papanikolaou , Styliani Sympardi , Maria Dafni , Antonia Alevizou , Alexia-Vasiliki Amvrazi , Errika Alexandrou , Kyprianos Archontoulis , Katerina Argyraki , Zoi Alexiou , Yakinthi Georgiou , Dimitra Gkogka , Evangelos J. Giamarellos-Bourboulis","doi":"10.1016/j.ijantimicag.2024.107405","DOIUrl":"10.1016/j.ijantimicag.2024.107405","url":null,"abstract":"<div><h3>Background</h3><div>Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the United States Food and Drug Administration for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/mL. We report the final results of the phase II open-label single-arm SAVE trial in a large population.</div></div><div><h3>Methods</h3><div>Patients with COVID-19 pneumonia and suPAR levels ≥ 6 ng/mL received subcutaneous anakinra 100 mg once daily for 10 days. The primary outcome was the incidence of SRF by day 14. Secondary outcomes were 30-day mortality, incidence of SRF according to time delay for start of treatment, safety, and associations with the inflammatory burden of the host.</div></div><div><h3>Results</h3><div>From March 2020 to March 2022, a total of 992 patients were enrolled. The incidence of SRF was 18.8%, similar to the results of the phase III pivotal SAVE-MOREtrial. The overall 30-day mortality was 9.5%. Participants were divided into 4 subgroups according to time delay between symptoms onset and start of anakinra. The incidence of SRF was similar for all subgroups. Serious adverse events were reported in 15.4%; only 3 were possibly related to anakinra. The most common adverse event was increased liver function tests. A post hoc comparison with the pivotal phase III trial showed similar anakinra outcomes among patient subgroups by levels of inflammatory mediators and D-dimers.</div></div><div><h3>Conclusions</h3><div>Results support the efficacy of anakinra as being similar to that of the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov, NCT04357366</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107405"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maheswaran Easwaran , Rajiv Gandhi Govindaraj , Misagh Naderi , Michal Brylinski , Mahanama De Zoysa , Hyun-Jin Shin
{"title":"Evaluating the antibacterial activity of engineered phage ФEcSw endolysin against multidrug-resistant Escherichia coli strain Sw1","authors":"Maheswaran Easwaran , Rajiv Gandhi Govindaraj , Misagh Naderi , Michal Brylinski , Mahanama De Zoysa , Hyun-Jin Shin","doi":"10.1016/j.ijantimicag.2024.107395","DOIUrl":"10.1016/j.ijantimicag.2024.107395","url":null,"abstract":"<div><h3>Objective</h3><div>The emergence of bacteriophage-encoded endolysins hold significant promise as novel antibacterial agents, particularly against the growing threat of antibiotic-resistant bacteria. Therefore, we investigated the phage ФEcSw endolysin to enhance the lytic activity against multi-drug-resistant <em>Escherichia coli</em> Sw1 through site-directed mutagenesis (SDM) guided by in silico identification of critical residues.</div></div><div><h3>Methods</h3><div>A computational analysis was conducted to elucidate the protein folding pattern, identify the active domains, and recognize critical residues of ФEcSw endolysin. Structural similarity-based docking simulations were employed to identify residues potentially involved in both recognition and cleavage of the bacterial peptidoglycan. Phage endolysin was amplified, cloned, expressed, and purified from phage ФEcSw. Pure endolysin (EL) activity was subsequently validated through SDM.</div></div><div><h3>Results</h3><div>Our studies revealed both open and closed conformations of ФEcSw endolysin within specific residue ranges (51–60 and 128–141). Notably, the active site was identified and contains the crucial catalytic residues, Glu19 and Asp34. A time-kill assay demonstrated that the holin (HL) – EL effectively reduced <em>E. coli</em> Sw1 growth by 46% within 12 h. Furthermore, treatment with HL, EL, and HL-EL significantly increased bacterial membrane permeability (11%, 74%, and 85%, respectively) within just 1 h. Importantly, SDM identified a double mutant (K19/H34) of the endolysin exhibiting the highest lytic activity compared to the wild-type and other mutants (E19D, E19K, D34E, and D34H) due to increase net charge from +3.23 to +6.29.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that phage endolysins and HLs or engineered endolysin hold significant potential as therapeutic agents to combat multidrug-resistant bacterial infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107395"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755100","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}
Philippe Gautret , Jean-Christophe Lagier , Philippe Parola , Van Thuan Hoang , Line Meddeb , Morgane Mailhe , Barbara Doudier , Johan Courjon , Valérie Giordanengo , Vera Esteves Vieira , Hervé Tissot Dupont , Stéphane Honoré , Philippe Colson , Eric Chabrière , Bernard La Scola , Jean-Marc Rolain , Philippe Brouqui , Didier Raoult
{"title":"Retraction notice to “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial” [International Journal of Antimicrobial Agents 56 (2020), 105949]","authors":"Philippe Gautret , Jean-Christophe Lagier , Philippe Parola , Van Thuan Hoang , Line Meddeb , Morgane Mailhe , Barbara Doudier , Johan Courjon , Valérie Giordanengo , Vera Esteves Vieira , Hervé Tissot Dupont , Stéphane Honoré , Philippe Colson , Eric Chabrière , Bernard La Scola , Jean-Marc Rolain , Philippe Brouqui , Didier Raoult","doi":"10.1016/j.ijantimicag.2024.107416","DOIUrl":"10.1016/j.ijantimicag.2024.107416","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107416"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894254","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}
Panteha Torabian , Navraj Singh , James Crawford , Gabriela Gonzalez , Nicholas Burgado , Martina Videva , Aidan Miller , Janai Perdue , Milena Dinu , Anthony Pietropaoli , Thomas Gaborski , Lea Vacca Michel
{"title":"Effect of clinically relevant antibiotics on bacterial extracellular vesicle release from Escherichia coli","authors":"Panteha Torabian , Navraj Singh , James Crawford , Gabriela Gonzalez , Nicholas Burgado , Martina Videva , Aidan Miller , Janai Perdue , Milena Dinu , Anthony Pietropaoli , Thomas Gaborski , Lea Vacca Michel","doi":"10.1016/j.ijantimicag.2024.107384","DOIUrl":"10.1016/j.ijantimicag.2024.107384","url":null,"abstract":"<div><div>Sepsis, a leading cause of death in hospitals, can be defined as a dysregulated host inflammatory response to infection, which can lead to tissue damage, organ failure and cardiovascular complications. Although there is no cure for sepsis, the condition is typically managed with broad-spectrum antibiotics to eliminate any potential bacterial source of infection. However, a potential side effect of antibiotic treatment is the enhanced release of bacterial extracellular vesicles (BEVs), membrane-bound nanoparticles containing proteins and other biological molecules from their parent bacterium. Some of the Gram-negative extracellular vesicle (EV) cargo, including peptidoglycan associated lipoprotein and outer membrane protein A, have been shown to induce both acute and chronic inflammation in host tissue. It was hypothesized that the antibiotic concentration and mechanism of action may affect the amount of released BEVs, which could potentially exacerbate the host inflammatory response. This study evaluated nine clinically relevant antibiotics for their effect on EV release from <em>Escherichia coli</em>. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycoside antibiotics caused less vesiculation. Further study is warranted to corroborate the correlation between an antibiotic's mechanism of action and its effect on EV release, but these results underline the importance of antibiotic choice when treating patients with sepsis.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107384"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}