Boqian Wang , Jingjing Fu , Yaqing He , Kexin Li , Guifang Hu , Mingda Hu , Xin Wang , Wanqiu Liu , Rui Zhang , Yuxin Wang , Buaijier Aimaiti , Xinru Zhao , Hongbin Song , Xiaofeng Hu , Hongguang Ren
{"title":"Molecular epidemiology and genomic insights into Enterobacter cloacae complex co-harbouring blaKPC and mcr: Implications for resistance gene transmission","authors":"Boqian Wang , Jingjing Fu , Yaqing He , Kexin Li , Guifang Hu , Mingda Hu , Xin Wang , Wanqiu Liu , Rui Zhang , Yuxin Wang , Buaijier Aimaiti , Xinru Zhao , Hongbin Song , Xiaofeng Hu , Hongguang Ren","doi":"10.1016/j.ijantimicag.2025.107602","DOIUrl":"10.1016/j.ijantimicag.2025.107602","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to systematically investigate the molecular epidemiology and genomic characteristics of <em>Enterobacter cloacae</em> complex (ECC) strains globally harbouring <em>bla</em><sub>KPC</sub> and <em>mcr</em>, as well as the co-existence of drug resistance genes. The goal is to provide insights and recommendations for monitoring clinical drug-resistant strains and super-resistant plasmids.</div></div><div><h3>Methods</h3><div>This study analysed 281 ECC isolates harbouring both <em>bla</em><sub>KPC</sub> and <em>mcr</em>, obtained from NCBI GenBank database (2003-2024) with whole-genome sequencing data. We constructed a phylogenetic tree of ECC strains for phylogenetic analysis. Resistance genes were identified using the ABRicate and CARD databases, and their distribution was examined. Plasmid replicon types for <em>bla</em><sub>KPC</sub> and <em>mcr</em> were analysed with PlasmidFinder, including upstream and downstream genetic environments of these genes.</div></div><div><h3>Results</h3><div>The predominant genotype combinations harbouring both <em>bla</em><sub>KPC</sub> and <em>mcr</em> are <em>bla</em><sub>KPC-3</sub> and <em>mcr-9.1</em>, followed by <em>bla</em><sub>KPC-4</sub> and <em>mcr-9.1</em>, with the dominant strain being <em>E. hormaechei</em> ssp. <em>xiangfangensis</em>. The IncHI2(2A) plasmid co-harbouring <em>bla</em><sub>KPC</sub> and <em>mcr-9</em> was mainly detected in genomes from the United States. Phylogenetic analysis indicated that the <em>bla</em><sub>KPC</sub>-<em>mcr-9</em>-IncHI2(2A) plasmids in ECC strains have a high genetic similarity to <em>mcr-9</em>-IncHI2(2A), suggesting that the latter may have acquired the additional highly transferable <em>bla</em><sub>KPC</sub>.</div></div><div><h3>Conclusions</h3><div>ECC strains have become an important reservoir cluster for <em>bla</em><sub>KPC</sub> and <em>mcr-9</em>, and the IncHI2(2A) plasmid is a potential vector for the horizontal co-transmission of carbapenem and colistin resistance genes. Effective monitoring should be implemented to assess the prevalence of co-harbouring <em>bla</em><sub>KPC</sub> and <em>mcr-9</em> in individual ECC isolates and even in single plasmid.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107602"},"PeriodicalIF":4.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953105","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}
Yu-Hao Liu , Ju Zhang , Deng-Hua Li , Yan-Peng Zhang , Jie Li , Qi-Qi Guo , Xiao-Jing Zhu , Yong-Quan Shi
{"title":"The impact of probiotics on Helicobacter pylori eradication with bismuth quadruple therapy: A systematic review and meta-analysis","authors":"Yu-Hao Liu , Ju Zhang , Deng-Hua Li , Yan-Peng Zhang , Jie Li , Qi-Qi Guo , Xiao-Jing Zhu , Yong-Quan Shi","doi":"10.1016/j.ijantimicag.2025.107600","DOIUrl":"10.1016/j.ijantimicag.2025.107600","url":null,"abstract":"<div><h3>Background</h3><div>Bismuth quadruple therapy (BQT) remains a cornerstone of first-line <em>Helicobacter pylori</em> eradication. However, its efficacy is increasingly undermined by antibiotic resistance, while frequent adverse events reduce its tolerability. Probiotics have been proposed as adjunctive agents to improve eradication outcomes and mitigate side effects, though their specific role in combination with BQT has yet to be fully established.</div></div><div><h3>Methods</h3><div>We conducted an extensive search of PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published through November 2024. Eligible studies compared <em>H. pylori</em> eradication rates and adverse events between probiotic-supplemented BQT (PBQT) and standard BQT in infected patients.</div></div><div><h3>Results</h3><div>Nineteen randomized controlled trials with 2973 samples were included. PBQT significantly improved <em>H. pylori</em> eradication rates compared to BQT alone (pooled odds ratio [OR] = 1.49, 95% confidence interval [CI] 1.20–1.85; <em>P</em> = 0.0004), with low heterogeneity (<em>I</em>² = 0%). Subgroup analyses demonstrated that both <em>Saccharomyces boulardii</em> (OR = 1.62; <em>P</em> < 0.05) and multi-strain probiotics (OR = 1.66; <em>P</em> < 0.05) significantly enhanced eradication rates. Concomitant administration of probiotics with antibiotics also yielded significant benefits (OR = 1.48, 95% CI 1.14–1.92; <em>P</em> = 0.003). PBQT demonstrated superior efficacy in the initial-treatment subgroup (OR = 1.48; <em>P</em> = 0.003) and among patients aged ≥18 y (OR = 1.47; <em>P</em> = 0.005). Regional subgroup analysis revealed a significant improvement in eradication rates for studies conducted in East Asia (OR = 1.66; <em>P</em> = 0.003). Antibiotic-specific subgroup analysis indicated a significant benefit of probiotics in the amoxicillin-clarithromycin BQT subgroup (OR = 1.59; <em>P</em> = 0.01). Overall, adverse events were significantly lower in the PBQT group (OR = 0.44, 95% CI 0.27–0.70, <em>P</em> = 0.0006), especially diarrhoea (OR = 0.33, 95% CI 0.21–0.52, <em>P</em> < 0.00001) and nausea (OR = 0.29, 95% CI 0.11–0.79, <em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>Adding probiotics, particularly <em>S. boulardii</em> or multi-strain combinations, to BQT significantly improves eradication efficacy and decreases treatment-related adverse events. PBQT represents a pragmatic optimization of current first-line regimens and supports its incorporation into clinical practice to improve <em>H. pylori</em> treatment outcomes.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107600"},"PeriodicalIF":4.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953123","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}
Xiaoying Yu , Yi Lu , Xin Shen , Xiaoxiang Hu , Kaixiang Jia , Weixian Lin , Zhiwei Li , Rendong Fang
{"title":"Therapeutic effect of taxifolin on bacterial meningitis associated with inhibition of PI3K/AKT and MAPK signalling","authors":"Xiaoying Yu , Yi Lu , Xin Shen , Xiaoxiang Hu , Kaixiang Jia , Weixian Lin , Zhiwei Li , Rendong Fang","doi":"10.1016/j.ijantimicag.2025.107601","DOIUrl":"10.1016/j.ijantimicag.2025.107601","url":null,"abstract":"<div><h3>Background</h3><div>Bacterial meningitis (BM) represents a severe infectious disease characterized by high mortality and neurological sequelae. The increasing prevalence of antimicrobial resistance has compromised antibiotic therapies, emphasizing an urgent need for alternative treatments. Taxifolin (TAX), a naturally occurring flavonoid, exhibits multiple bioactivities, yet its role in BM remains unknown.</div></div><div><h3>Purpose</h3><div>This study investigated the therapeutic effects of TAX in BM and explored its underlying molecular mechanisms.</div></div><div><h3>Study design and methods</h3><div>Using both in vitro and in vivo approaches, we established BM models with extraintestinal pathogenic <em>Escherichia coli</em> and <em>Streptococcus suis</em>. The therapeutic efficacy of TAX was assessed through comprehensive analyses of pathological changes and inflammatory responses. Molecular mechanisms were investigated using multiple approaches, including network pharmacology, Western blotting, drug affinity-responsive target stability assay, and cellular thermal shift assay.</div></div><div><h3>Results</h3><div>TAX significantly inhibited bacteria-induced cell death in microglia and brain endothelial cells, reduced microglial inflammatory responses, and protected endothelial tight junction proteins in vitro. In mice, TAX markedly reduced mortality, alleviated tissue damage, and suppressed inflammatory responses. The protective effects of TAX were associated with the inhibition of PI3K/AKT and MAPK pathways, with AKT identified as its direct target.</div></div><div><h3>Conclusions</h3><div>Our findings identify TAX as a potential therapeutic agent for BM treatment, with its protective effects associated with the inhibition of PI3K/AKT and MAPK pathways. These results provide a foundation for the further development of TAX-based interventions against BM.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107601"},"PeriodicalIF":4.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953137","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":"Structural and functional features of Klebsiella pneumoniae capsular degradation by the phage depolymerase KP32gp38: Implications for vaccination against K. pneumoniae","authors":"Valeria Napolitano , Mario Privitera , Zuzanna Drulis-Kawa , Daniela Marasco , Silvia Fallarini , Rita Berisio , Flavia Squeglia","doi":"10.1016/j.ijantimicag.2025.107596","DOIUrl":"10.1016/j.ijantimicag.2025.107596","url":null,"abstract":"<div><h3>Objective</h3><div><em>Klebsiella pneumoniae Przondovirus</em> KP32 presents a complex capsular degradation machinery comprised of two serotype-specific depolymerases, KP32gp38 and KP32gp37.</div></div><div><h3>Methods</h3><div>In this work, we performed capsular polysaccharide (CPS) degradation assays combined with mass spectrometry approaches to identify the reaction product of K21 serotype CPS degradation by KP32gp38. We determined the crystal structure of the KP32gp38 depolymerase in complex with the identified degradation product, a pyruvated pentasaccharide, called K21-pyr5.</div></div><div><h3>Results</h3><div>The structure showed that K21-pyr5 binds to the inter-chain catalytic site, allowing the identification of important residues for CPS recognition. Importantly, we observed that the production of K21-pyr5 through CPS degradation by KP32gp38 is able to induce the maturation and differentiation of monocyte-derived dendritic cells, which, in turn, induce lymphocyte proliferation and Th polarization. By employing a T7 phage of <em>Escherichia coli</em> analogy, we were able to provide insights into the portal assembly of the <em>Przondovirus</em> K32. Our modeling studies suggest that the KP32 portal, attached to its icosahedral capsid shell, carries 12 depolymerase molecules on a single virion, arranged in 6 branches; in each branch, KP32gp38 depolymerase adheres to KP32gp37, which is directly connected to the phage portal.</div></div><div><h3>Conclusions</h3><div>Overall, our results suggest that depolymerases act as anti-virulent agents, not only by depleting the bacteria of their CPS but also by producing immunostimulatory CPS degradation products. This indicates the use of CPS degradation products by depolymerases as potential antigens in <em>K. pneumoniae</em> vaccination strategies.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107596"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953172","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}
Shuji Gao , Yingying Quan , Shenao Song , Wenjie Jin , Zhiheng Chang , Baobao Liu , Yuxin Wang , Li Yi , Yang Wang
{"title":"Disrupting bacterial metabolism by targeting LDH reverses Streptococcus suis aminoglycoside resistance","authors":"Shuji Gao , Yingying Quan , Shenao Song , Wenjie Jin , Zhiheng Chang , Baobao Liu , Yuxin Wang , Li Yi , Yang Wang","doi":"10.1016/j.ijantimicag.2025.107599","DOIUrl":"10.1016/j.ijantimicag.2025.107599","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of drug-resistant <em>Streptococcus suis</em> (<em>S. suis</em>), driven primarily by antibiotic overuse in veterinary medicine and agriculture practices, threatens global public health. Antibiotic adjuvants that potentiate existing drugs offer a promising strategy to combat resistance.</div></div><div><h3>Methods</h3><div>We screened two small molecules targeting lactic dehydrogenase of <em>S. suis</em>. Hit compounds panaxadiol (PD) and vitamin D<sub>2</sub> (VD<sub>2</sub>) were evaluated for metabolic modulation via aerobic respiration assays, NADH quantification, proton motive force (PMF) measurements, and metabonomics analysis. Aminoglycoside uptake and bactericidal activity were assessed in vitro and in vivo. All data are presented as mean ± SD from three independent experiments, and significance was determined by unpaired <em>t</em> tests (*<em>P</em> < 0.05, **<em>P</em> < 0.01, ***<em>P</em> < 0.001).</div></div><div><h3>Results</h3><div>PD and VD<sub>2</sub> inhibited <em>S. suis</em> lactic dehydrogenase, suppressing anaerobic metabolism and redirecting pyruvate to the tricarboxylic acid cycle. This shift increased NADH production, amplified PMF, and enhanced uptake of PMF-dependent aminoglycosides. Both compounds synergized with aminoglycosides, significantly improving bactericidal efficacy against <em>S. suis</em> in vitro and in animal models.</div></div><div><h3>Conclusions</h3><div>Targeting <em>S. suis</em> metabolic pathways with PD or VD<sub>2</sub> restores aminoglycoside susceptibility, offering an adjuvant strategy to counter antibiotic resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107599"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953115","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}
Shuxiu Liu , Lei Fang , Weidong Zhu , Hao Xu , Xiaobing Guo , Shaojie Gu , Shuang Li , Yanhao Shen , Lin Zhang , Beiwen Zheng
{"title":"Emergence of a novel transferable megaplasmid driving blaVIM-24 and tmexCD3-toprJ3 dissemination in clinical Pseudomonas fulva isolates","authors":"Shuxiu Liu , Lei Fang , Weidong Zhu , Hao Xu , Xiaobing Guo , Shaojie Gu , Shuang Li , Yanhao Shen , Lin Zhang , Beiwen Zheng","doi":"10.1016/j.ijantimicag.2025.107594","DOIUrl":"10.1016/j.ijantimicag.2025.107594","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the genetic characteristics and transmission mechanism of clinical <em>Pseudomonas</em> <em>fulva</em> isolates with transferable megaplasmid co-carrying <em>bla</em><sub>VIM−24</sub> and <em>tmexCD3</em>-<em>toprJ3</em>.</div></div><div><h3>Methods</h3><div>Bacterial identification was performed using MALDI-TOF/MS, and antimicrobial susceptibility testing was carried out using agar dilution and broth microdilution. The genetic context of drug resistance genes and plasmid characteristics was analyzed by S1-PFGE, Southern blotting, conjugation experiments, and whole-genome sequencing analysis. Comparative genomics analysis of the plasmids and genetic context was conducted by using BLAST Ring Image Generator (BRIG) and Easyfig 2.3. Phylogenetic analysis of <em>P</em>. <em>fulva</em> strains and pJBCL41-like megaplasmids was performed by Snipy and Mega, respectively.</div></div><div><h3>Results</h3><div>Clinical <em>P</em>. <em>fulva</em> strains, ZDHY316 and ZDHY414, with transferable megaplasmids co-carrying <em>bla</em><sub>VIM−24</sub> and <em>tmexCD3</em>-<em>toprJ3</em>. The megaplasmids pVIM-24-ZDHY316 and pVIM-24-ZDHY414 carry multiple drug-resistant genes and integrate numerous integrons and transposon truncations from different origins. ΔTn6855-ΔTn6758 is the new discoovered co-transfer module carrying <em>nfxB</em>-<em>mexCD</em>-<em>oprJ</em>, which only exists in chromosomes and megaplasmids. Phylogenetic analysis of pJBCL41-like megaplasmids showed their evolution towards carrying more drug-resistance genes and mobile genetic elements. Additionally, ZDHY316 has another transferable plasmid, pVIM-1-ZDHY316, which carries the novel integron In<em>2008</em> with the GCA of 5ʹCS- <em>bla</em><sub>VIM-1</sub>-<em>aac(6ʹ)-Ib</em>-3ʹCS. Phylogenetic analysis of <em>P</em>. <em>fulva</em> strains showed that China is the country with the most <em>P</em>. <em>fulva</em> isolated clinically, with strains prevalent and evolving in hospitals.</div></div><div><h3>Conclusions</h3><div>The mosaic structure of the megaplasmid, characterized by integrons and transposons, underscores its role in resistance gene dissemination and highlights the adaptability of non-standard pathogens like <em>P</em>. <em>fulva</em>. The horizontal transfer potential of this megaplasmid poses a significant challenge to clinical infection control. Enhanced surveillance of non-standard pathogens and their plasmids is essential.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107594"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953107","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}
Miaoran Wang , Ying Wu , Ying Xi , Lichao Fan , Fengshuo Sun , Gang Zhou , Wei Wang , Yanhong Yu , Jiao Sun , Xue Yang , Jun Tang , Lifeng Li , Yu Chen
{"title":"Enhanced Targeted NGS Assay for Comprehensive Diagnosis in Tuberculosis and Drug-Resistant Tuberculosis Patients","authors":"Miaoran Wang , Ying Wu , Ying Xi , Lichao Fan , Fengshuo Sun , Gang Zhou , Wei Wang , Yanhong Yu , Jiao Sun , Xue Yang , Jun Tang , Lifeng Li , Yu Chen","doi":"10.1016/j.ijantimicag.2025.107598","DOIUrl":"10.1016/j.ijantimicag.2025.107598","url":null,"abstract":"<div><h3>Background</h3><div>Accurate and timely diagnosis of tuberculosis (TB) and drug-resistant TB is crucial; however, current methods have limitations in sensitivity and scope, especially for detecting drug resistance and differentiating other respiratory pathogens.</div></div><div><h3>Methods</h3><div>We developed a multiplex PCR-based targeted next-generation sequencing (tNGS) assay and validated its analytical performance, including limit of detection (LoD), precision, and resistance to interference. A single-centre prospective study was conducted with 181 suspected TB patients to evaluate the assay’s clinical performance using bronchoalveolar lavage or sputum samples, compared against microbiological culture and Xpert MTB/RIF.</div></div><div><h3>Results</h3><div>The tNGS assay demonstrated a low LoD of 10 copies/mL for TB and other respiratory pathogens, with high precision and resistance to interference. In clinical validation, it achieved 94.94 % sensitivity in confirmed TB cases and showed a 92.86 % positive percent agreement with Xpert MTB/RIF for rifampicin resistance, while also identifying additional mutations. The assay accurately detected nontuberculous mycobacteria (NTM) and other respiratory pathogens, aiding differential diagnosis.</div></div><div><h3>Conclusion</h3><div>The tNGS assay provides reliable detection of TB, drug-resistant mutations, and respiratory pathogens, including NTM, thereby enhancing differential diagnosis and supporting effective treatment strategies in the management of patients with suspected TB.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107598"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953088","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}