Pub Date : 2025-12-11DOI: 10.1016/j.ijmm.2025.151694
Tanvi Somiah, Priyodip Paul, Sarah Pilheden, James Trumbo, Ann-Beth Jonsson
To date, various probiotic lactobacilli have been tested against Helicobacter pylori. However, a detailed molecular analysis of the various signaling pathways and their associated anti-proliferative activity remains poorly understood. In our previously published research, a disintegrin and metalloprotease 17 (ADAM17) was proposed as a key target for anti-inflammatory activity in H. pylori-infected host macrophages. Therefore, in this study, the anti-H. pylori activity of selected lactobacilli was assessed based on expression of ADAM17 and two of its targets, heparin-binding EGF-like growth factor (HBEGF) and transforming growth factor-alpha (TGF-α), which were measured in gastric epithelial cells. For this purpose, lactobacilli and H. pylori were either added together to the AGS cells (coincubation), or the cells were first exposed to lactobacilli before H. pylori infection (preincubation). In coincubation assays, lactobacilli had no effect on H. pylori-mediated ADAM17, HBEGF, and TGF-α upregulation at the protein level. However, in preincubation assays, L. gasseri downregulated the expression of ADAM17 and its substrates. Furthermore, the proliferation data demonstrated that L. gasseri suppressed H. pylori-induced cellular progression. Using an in vivo mouse model, the anti-inflammatory activity of selected lactobacilli was tested by measuring blood cytokine profiles and tissue staining. L. gasseri significantly decreased the levels of the pro-inflammatory cytokine TNF and reduced immune cell infiltration in stained gastric tissues. Together, these findings suggest that certain lactobacilli can counteract the H. pylori-mediated induction of HBEGF and TGF-α expression, and indicate that ADAM17 could be targeted to inhibit the cancer-related effects of H. pylori.
{"title":"Lactobacillus gasseri suppresses the Helicobacter pylori-induced expression of the proliferation-associated factors HBEGF and TGF-α in gastric host cells","authors":"Tanvi Somiah, Priyodip Paul, Sarah Pilheden, James Trumbo, Ann-Beth Jonsson","doi":"10.1016/j.ijmm.2025.151694","DOIUrl":"10.1016/j.ijmm.2025.151694","url":null,"abstract":"<div><div>To date, various probiotic lactobacilli have been tested against <em>Helicobacter pylori</em>. However, a detailed molecular analysis of the various signaling pathways and their associated anti-proliferative activity remains poorly understood. In our previously published research, a disintegrin and metalloprotease 17 (ADAM17) was proposed as a key target for anti-inflammatory activity in <em>H. pylori</em>-infected host macrophages. Therefore, in this study, the anti-<em>H. pylori</em> activity of selected lactobacilli was assessed based on expression of ADAM17 and two of its targets, heparin-binding EGF-like growth factor (HBEGF) and transforming growth factor-alpha (TGF-α), which were measured in gastric epithelial cells. For this purpose, lactobacilli and <em>H. pylori</em> were either added together to the AGS cells (coincubation), or the cells were first exposed to lactobacilli before <em>H. pylori</em> infection (preincubation). In coincubation assays, lactobacilli had no effect on <em>H. pylori</em>-mediated ADAM17, HBEGF, and TGF-α upregulation at the protein level. However, in preincubation assays, <em>L. gasseri</em> downregulated the expression of ADAM17 and its substrates. Furthermore, the proliferation data demonstrated that <em>L. gasseri</em> suppressed <em>H. pylori</em>-induced cellular progression. Using an <em>in vivo</em> mouse model, the anti-inflammatory activity of selected lactobacilli was tested by measuring blood cytokine profiles and tissue staining. <em>L. gasseri</em> significantly decreased the levels of the pro-inflammatory cytokine TNF and reduced immune cell infiltration in stained gastric tissues. Together, these findings suggest that certain lactobacilli can counteract the <em>H. pylori</em>-mediated induction of HBEGF and TGF-α expression, and indicate that ADAM17 could be targeted to inhibit the cancer-related effects of <em>H. pylori</em>.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151694"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.ijmm.2025.151696
Shengying Lou , Wei Jin , Minyang He , Chunyan Dai , Zhiqiang Zhu , Peng Li , Jichun Han , Xingru Chen , Miaolian Wu , Xiangcheng Fan , Xiaojun Xu
Background
Dehydroeffusol (DHE) is a natural phenanthrene compound derived from Juncus effusus L., traditionally used for its antimicrobial properties. Despite its historical use, its antibacterial efficacy and underlying mechanisms have not been fully explored.
Objectives
To evaluate the antibacterial activity, safety profile, and mechanism of action of DHE against Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), and to assess its potential as a therapeutic agent.
Methods
DHE was isolated and its antibacterial effects were assessed using broth microdilution, time-kill assays, and biofilm inhibition assays. The cytotoxicity and hemolytic activity of DHE were evaluated in vitro using several cell lines and red blood cells. Mechanistic studies included scanning electron microscopy, membrane potential and permeability assays, network pharmacology analysis, molecular docking, and untargeted metabolomic profiling.
Results
DHE exhibited appreciable bactericidal activity against S. aureus and MRSA with minimal cytotoxicity. It inhibited biofilm formation, disrupted bacterial membranes, and maintained bactericidal activity without rapid resistance, while synergizing with ciprofloxacin, streptomycin, and azithromycin. Network pharmacology and docking identified 56 infection-related targets (hub proteins EGFR, BCL2, HSP90AA1/B1, ESR1, SRC) enriched in PI3K–Akt/ErbB/EGFR pathways, supporting additional modulation of host infection-related signaling. In MRSA, untargeted metabolomics showed broad disturbances in amino acid, energy, and nucleotide metabolism, indicating disruption of essential biosynthetic and energy pathways. In vivo, DHE significantly reduced bacterial load and alleviated tissue damage in a murine MRSA infection model, demonstrating measurable protective effects.
Conclusions
DHE is a promising natural antimicrobial agent with notable activity against S. aureus and MRSA. Its mechanism of action involves membrane disruption and biofilm inhibition, along with preliminary safety in vitro, supporting its potential for further development as an effective antimicrobial agent.
{"title":"Dehydroeffusol from Juncus effusus L. exhibits antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo","authors":"Shengying Lou , Wei Jin , Minyang He , Chunyan Dai , Zhiqiang Zhu , Peng Li , Jichun Han , Xingru Chen , Miaolian Wu , Xiangcheng Fan , Xiaojun Xu","doi":"10.1016/j.ijmm.2025.151696","DOIUrl":"10.1016/j.ijmm.2025.151696","url":null,"abstract":"<div><h3>Background</h3><div>Dehydroeffusol (DHE) is a natural phenanthrene compound derived from <em>Juncus effusus L.</em>, traditionally used for its antimicrobial properties. Despite its historical use, its antibacterial efficacy and underlying mechanisms have not been fully explored.</div></div><div><h3>Objectives</h3><div>To evaluate the antibacterial activity, safety profile, and mechanism of action of DHE against <em>Staphylococcus aureus</em> (<em>S. aureus</em>), including methicillin-resistant <em>S. aureus</em> (MRSA), and to assess its potential as a therapeutic agent.</div></div><div><h3>Methods</h3><div>DHE was isolated and its antibacterial effects were assessed using broth microdilution, time-kill assays, and biofilm inhibition assays. The cytotoxicity and hemolytic activity of DHE were evaluated <em>in vitro</em> using several cell lines and red blood cells. Mechanistic studies included scanning electron microscopy, membrane potential and permeability assays, network pharmacology analysis, molecular docking, and untargeted metabolomic profiling.</div></div><div><h3>Results</h3><div>DHE exhibited appreciable bactericidal activity against <em>S. aureus</em> and MRSA with minimal cytotoxicity. It inhibited biofilm formation, disrupted bacterial membranes, and maintained bactericidal activity without rapid resistance, while synergizing with ciprofloxacin, streptomycin, and azithromycin. Network pharmacology and docking identified 56 infection-related targets (hub proteins EGFR, BCL2, HSP90AA1/B1, ESR1, SRC) enriched in PI3K–Akt/ErbB/EGFR pathways, supporting additional modulation of host infection-related signaling. In MRSA, untargeted metabolomics showed broad disturbances in amino acid, energy, and nucleotide metabolism, indicating disruption of essential biosynthetic and energy pathways. <em>In vivo</em>, DHE significantly reduced bacterial load and alleviated tissue damage in a murine MRSA infection model, demonstrating measurable protective effects.</div></div><div><h3>Conclusions</h3><div>DHE is a promising natural antimicrobial agent with notable activity against <em>S. aureus</em> and MRSA. Its mechanism of action involves membrane disruption and biofilm inhibition, along with preliminary safety <em>in vitro</em>, supporting its potential for further development as an effective antimicrobial agent.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151696"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.ijmm.2025.151695
Shihui Yuan , Ping Yan , Huimin Su , Ayesha Serwat , Yujie Li , Baolin Sun
Staphylococcus aureus is a well-known pathogenic bacterium that can produce a variety of virulence factors that cause disease in humans. RpiRB is a regulator of metabolic response, whose regulatory role in the virulence of S. aureus is largely unknown. In this study, we demonstrated that the disruption of rpiRB led to down-regulation of the transcription levels of agr-related virulence factors, and reduced the hemolytic activity of methicillin-resistance S. aureus (MRSA). In addition, we also found that RpiRB was involved in regulating the inflammatory response of the host. A mouse subcutaneous abscess model showed that the pathogenicity of the strain was significantly reduced after the destruction of rpiRB. Interestingly, RpiRB enhanced the pathogenic capacity of S. aureus in an agr-dependent manner, while it was directly inhibited by SarA. This study aims to highlight the role of RpiRB in the regulation of the pathogenicity of S. aureus, so as to provide theoretical references for illustrating the infection mechanism and coping strategies of S. aureus.
{"title":"Metabolite-responsive regulator RpiRB modulates Staphylococcus aureus pathogenicity via regulation of agr expression","authors":"Shihui Yuan , Ping Yan , Huimin Su , Ayesha Serwat , Yujie Li , Baolin Sun","doi":"10.1016/j.ijmm.2025.151695","DOIUrl":"10.1016/j.ijmm.2025.151695","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> is a well-known pathogenic bacterium that can produce a variety of virulence factors that cause disease in humans. RpiRB is a regulator of metabolic response, whose regulatory role in the virulence of <em>S. aureus</em> is largely unknown. In this study, we demonstrated that the disruption of <em>rpiRB</em> led to down-regulation of the transcription levels of <em>agr</em>-related virulence factors, and reduced the hemolytic activity of methicillin-resistance <em>S. aureus</em> (MRSA). In addition, we also found that RpiRB was involved in regulating the inflammatory response of the host. A mouse subcutaneous abscess model showed that the pathogenicity of the strain was significantly reduced after the destruction of <em>rpiRB</em>. Interestingly, RpiRB enhanced the pathogenic capacity of <em>S. aureus</em> in an <em>agr</em>-dependent manner, while it was directly inhibited by SarA. This study aims to highlight the role of RpiRB in the regulation of the pathogenicity of <em>S. aureus</em>, so as to provide theoretical references for illustrating the infection mechanism and coping strategies of <em>S. aureus</em>.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151695"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.ijmm.2025.151692
Valentin Lemoine , Simon Rolland , Sophie Reissier , David Luque Paz , Marion Souffez , Mathilde Favalelli , Victor Scavazzin , Julie Brousseau , Claudie Lamoureux , Caroline Piau , Vincent Cattoir , François Caméléna , Béatrice Berçot , Geneviève Héry-Arnaud
Background
Gonococcal infections are sexually-transmitted infections (STIs), which in 0.5–3 % of cases, can progress to disseminated infections (DGI). This study aimed to characterize the epidemiology of septic arthritis and tenosynovitis caused by Neisseria gonorrhoeae, the two most common clinical manifestations of DGI (30–90 %).
Methods
A retrospective observational study was conducted in two French referral hospitals from June 2014 to June 2024. Adult patients treated for septic arthritis due to N. gonorrhoeae with a positive culture of joint fluid were included.
Results
We identified ten cases (eight males and two females) with a mean age of 44 years. The infected joints were the wrist, knee, thumb, elbow, ankle, and hip. On average, it took 13 days from the onset of symptoms to the administration of appropriate antibiotic treatment. Among the ten cases, seven strains were available. Of these, five were resistant to fluoroquinolones and six to tetracyclines. All strains were susceptible to third-generation cephalosporins. All patients received ceftriaxone as first-line therapy and achieved complete recovery in 70 % (7/10) of cases at the one-year follow-up. Whole genome sequencing identified virulence-associated alleles, such as porB1a, but no clustering of hypervirulent clones was observed.
Conclusions
Our findings highlight the variety of joints affected by septic arthritis caused by N. gonorrhoeae, as well as high level of resistance to both fluoroquinolones and tetracyclines. These results emphasize the importance of vigilance when diagnosing and managing gonococcal infections, particularly in high-risk populations, and highlight the need for further research into alternative treatments to address emerging resistance.
{"title":"Epidemiology of gonococcal arthritis in Brittany - France (EpGAr study)","authors":"Valentin Lemoine , Simon Rolland , Sophie Reissier , David Luque Paz , Marion Souffez , Mathilde Favalelli , Victor Scavazzin , Julie Brousseau , Claudie Lamoureux , Caroline Piau , Vincent Cattoir , François Caméléna , Béatrice Berçot , Geneviève Héry-Arnaud","doi":"10.1016/j.ijmm.2025.151692","DOIUrl":"10.1016/j.ijmm.2025.151692","url":null,"abstract":"<div><h3>Background</h3><div>Gonococcal infections are sexually-transmitted infections (STIs), which in 0.5–3 % of cases, can progress to disseminated infections (DGI). This study aimed to characterize the epidemiology of septic arthritis and tenosynovitis caused by <em>Neisseria gonorrhoeae</em>, the two most common clinical manifestations of DGI (30–90 %).</div></div><div><h3>Methods</h3><div>A retrospective observational study was conducted in two French referral hospitals from June 2014 to June 2024. Adult patients treated for septic arthritis due to <em>N. gonorrhoeae</em> with a positive culture of joint fluid were included.</div></div><div><h3>Results</h3><div>We identified ten cases (eight males and two females) with a mean age of 44 years. The infected joints were the wrist, knee, thumb, elbow, ankle, and hip. On average, it took 13 days from the onset of symptoms to the administration of appropriate antibiotic treatment. Among the ten cases, seven strains were available. Of these, five were resistant to fluoroquinolones and six to tetracyclines. All strains were susceptible to third-generation cephalosporins. All patients received ceftriaxone as first-line therapy and achieved complete recovery in 70 % (7/10) of cases at the one-year follow-up. Whole genome sequencing identified virulence-associated alleles, such as <em>porB1a</em>, but no clustering of hypervirulent clones was observed.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the variety of joints affected by septic arthritis caused by <em>N. gonorrhoeae</em>, as well as high level of resistance to both fluoroquinolones and tetracyclines. These results emphasize the importance of vigilance when diagnosing and managing gonococcal infections, particularly in high-risk populations, and highlight the need for further research into alternative treatments to address emerging resistance.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151692"},"PeriodicalIF":3.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ijmm.2025.151689
Zhengyu Luo , Yating Ning , Rongchen Dai , Ailifeire Ainiwaer , Yanhong Li , Ruike Zhang , Meng Xiao , Xiaoxi Wang , Yang Yang , Yuyan Huang , Dingding Li , Lingli Liu , Roujie Huang , Tingying Xu , Yingchun Xu , Zhiyong Liu , Li Zhang , Tianshu Sun
Fungal infections pose a growing global threat, particularly due to the emergence of multidrug-resistant pathogens. This study reports the first globally documented case of a Wickerhamomyces anomalus isolate (XN272) displaying dual high-level resistance to all tested azoles and echinocandins. Genomic analysis of the strain, which was isolated from a bloodstream infection in a 64-year-old male post-pancreatic surgery, identified two key resistance mechanisms: the azole target gene ERG11 harbored missense mutations (Y140H, K151R) and tandem copy number variations, while the echinocandin target gene FKS1 carried an F665S mutation. Transcriptomic profiling under antifungal exposure suggested an additional resistance mechanism, the upregulation of membrane-associated genes and efflux transporters (e.g., FLU1). Strain XN272 exhibited robust biofilm-forming capacity, a trait linked to reduced drug susceptibility. Despite its resistant phenotype, virulence assessments in immunosuppressed mice showed comparable tissue colonization and clearance rates to strain ATCC 8168. The discovery of pan-azole and pan-echinocandin resistance in W. anomalus highlights the expanding landscape of antifungal resistance and its clinical management challenges.
{"title":"A pan-azole and pan-echinocandin resistant Wickerhamomyces anomalus isolate causing bloodstream infection: ERG11Y140F, K151R with copy number variation and FKS1 F665S mutation","authors":"Zhengyu Luo , Yating Ning , Rongchen Dai , Ailifeire Ainiwaer , Yanhong Li , Ruike Zhang , Meng Xiao , Xiaoxi Wang , Yang Yang , Yuyan Huang , Dingding Li , Lingli Liu , Roujie Huang , Tingying Xu , Yingchun Xu , Zhiyong Liu , Li Zhang , Tianshu Sun","doi":"10.1016/j.ijmm.2025.151689","DOIUrl":"10.1016/j.ijmm.2025.151689","url":null,"abstract":"<div><div>Fungal infections pose a growing global threat, particularly due to the emergence of multidrug-resistant pathogens. This study reports the first globally documented case of a <em>Wickerhamomyces anomalus</em> isolate (XN272) displaying dual high-level resistance to all tested azoles and echinocandins. Genomic analysis of the strain, which was isolated from a bloodstream infection in a 64-year-old male post-pancreatic surgery, identified two key resistance mechanisms: the azole target gene <em>ERG11</em> harbored missense mutations (Y140H, K151R) and tandem copy number variations, while the echinocandin target gene <em>FKS1</em> carried an F665S mutation. Transcriptomic profiling under antifungal exposure suggested an additional resistance mechanism, the upregulation of membrane-associated genes and efflux transporters (e.g., <em>FLU1</em>). Strain XN272 exhibited robust biofilm-forming capacity, a trait linked to reduced drug susceptibility. Despite its resistant phenotype, virulence assessments in immunosuppressed mice showed comparable tissue colonization and clearance rates to strain ATCC 8168. The discovery of pan-azole and pan-echinocandin resistance in <em>W. anomalus</em> highlights the expanding landscape of antifungal resistance and its clinical management challenges.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151689"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ijmm.2025.151686
Ying Wang , Zhihan Xiao , Huimin Xi , Qing Zhu , Peng Liu , Rui Zhao
Objectives
This study aimed to characterize the molecular epidemiology, antimicrobial resistance, virulence profiles, and clinical outcomes of Methicillin-resistant Staphylococcus aureus (MRSA) infections among intensive care unit (ICU) patients in southern China.
Methods
A total of 104 non-duplicate MRSA isolates were collected from ICU patients at a tertiary hospital between 2021 and 2024. Whole-genome sequencing was used to determine molecular characteristics. Antimicrobial susceptibility, biofilm formation, and hemolytic activity were conducted. Clinical data were analyzed to evaluate associations between MRSA lineages and patient outcomes.
Results
Eight clonal complexes and 16 sequence types were identified, with Clonal Complex (CC)5 (31.7 %), CC59 (20.2 %), and CC398 (18.3 %) being the most predominant. The dominant clones, namely CC5-ST5-SCCmec II-agr II, CC398-ST398-SCCmec V-agr I, and CC59-ST59-SCCmec IV-agr I, each exhibited distinct phylogenetic clustering patterns and resistance patterns. Notably, ST764, a variant of ST5, showed extensive multidrug resistance and robust biofilm-forming capacity, while ST59 isolates displayed the highest hemolytic activity. ST5 and ST764 exhibited the broadest resistance profiles. Virulence genes hla, psmα1–4 and psmβ1 present in all isolates, while tst was more frequent in CC5 and associated with higher 30-day death rate (P = 0.038). CC5 infections were linked to worse outcomes, with a death rate of 45.5 %. Renal insufficiency (P < 0.001) and malignancy (P = 0.011) were independent predictors of 30-day death rate.
Conclusion
ICU-derived MRSA isolates in southern China display considerable molecular diversity and varying resistance and virulence profiles. CC5, especially ST764, is associated with multidrug resistance and poor clinical outcomes, highlighting the need for enhanced infection control in ICUs.
{"title":"Clinical characteristics and whole-genome analysis of methicillin-resistant Staphylococcus aureus in ICU patients from a tertiary hospital in southern China","authors":"Ying Wang , Zhihan Xiao , Huimin Xi , Qing Zhu , Peng Liu , Rui Zhao","doi":"10.1016/j.ijmm.2025.151686","DOIUrl":"10.1016/j.ijmm.2025.151686","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to characterize the molecular epidemiology, antimicrobial resistance, virulence profiles, and clinical outcomes of Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) infections among intensive care unit (ICU) patients in southern China.</div></div><div><h3>Methods</h3><div>A total of 104 non-duplicate MRSA isolates were collected from ICU patients at a tertiary hospital between 2021 and 2024. Whole-genome sequencing was used to determine molecular characteristics. Antimicrobial susceptibility, biofilm formation, and hemolytic activity were conducted. Clinical data were analyzed to evaluate associations between MRSA lineages and patient outcomes.</div></div><div><h3>Results</h3><div>Eight clonal complexes and 16 sequence types were identified, with Clonal Complex (CC)5 (31.7 %), CC59 (20.2 %), and CC398 (18.3 %) being the most predominant. The dominant clones, namely CC5-ST5-SCC<em>mec</em> II-<em>agr</em> II, CC398-ST398-SCC<em>mec</em> V-<em>agr</em> I, and CC59-ST59-SCC<em>mec</em> IV-<em>agr</em> I, each exhibited distinct phylogenetic clustering patterns and resistance patterns. Notably, ST764, a variant of ST5, showed extensive multidrug resistance and robust biofilm-forming capacity, while ST59 isolates displayed the highest hemolytic activity. ST5 and ST764 exhibited the broadest resistance profiles. Virulence genes <em>hla, psmα1–4</em> and <em>psmβ1</em> present in all isolates, while <em>tst</em> was more frequent in CC5 and associated with higher 30-day death rate (<em>P</em> = 0.038). CC5 infections were linked to worse outcomes, with a death rate of 45.5 %. Renal insufficiency (<em>P</em> < 0.001) and malignancy (<em>P</em> = 0.011) were independent predictors of 30-day death rate.</div></div><div><h3>Conclusion</h3><div>ICU-derived MRSA isolates in southern China display considerable molecular diversity and varying resistance and virulence profiles. CC5, especially ST764, is associated with multidrug resistance and poor clinical outcomes, highlighting the need for enhanced infection control in ICUs.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151686"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ijmm.2025.151688
Florence Crombé , Frederic Auvray , Angela H.A.M. van Hoek , Bavo Verhaegen , Sigrid C.J. De Keersmaecker , Carolina Silva Nodari , Aurélie Cointe , Jacques Mainil , Caroline Willis , Gro S. Johannessen , Ralph Litjens , Joost Stassen , Denis Piérard
The increased detection of Shiga toxin-producing Escherichia coli (STEC) O113:H4 among human cases in Belgium questions the importance of this serotype as an emerging pathogen. However, detailed information focusing on serotype O113:H4 from human and non-human sources remains limited. We analysed a collection of 140 STEC O113:H4 isolates and their whole genomes, originating from animal hosts (cattle, deer, goats, and sheep), food, and humans, to determine their genetic relationship and assess key virulence genes. All STEC O113:H4 genomes lacked the locus of enterocyte effacement (LEE) and belonged to Pasteur Sequence Type (pST) 367 complex, dominated by pST367 (ehxA-, stx2d+) and pST1729 (ehxA+, stx2b+). Compared to stx2d+ isolates, stx2b+ isolates carried on median more virulence factors, which might thus contribute to enhanced pathogenicity. Besides, humans appear to be infected with distinct subgroups of STEC O113:H4 carrying distinct stx subtypes and originating from potentially different sources: deer, goats, and sheep for STEC carrying stx2b (alone or in combination with stx1c) and mainly cattle for STEC carrying stx2d. Our results call for improved understanding and continuous surveillance of emerging STEC O113:H4.
{"title":"Emergence and genetic heterogeneity of STEC O113:H4: insights from whole-genome sequences of isolates across human and non-human sources","authors":"Florence Crombé , Frederic Auvray , Angela H.A.M. van Hoek , Bavo Verhaegen , Sigrid C.J. De Keersmaecker , Carolina Silva Nodari , Aurélie Cointe , Jacques Mainil , Caroline Willis , Gro S. Johannessen , Ralph Litjens , Joost Stassen , Denis Piérard","doi":"10.1016/j.ijmm.2025.151688","DOIUrl":"10.1016/j.ijmm.2025.151688","url":null,"abstract":"<div><div>The increased detection of Shiga toxin-producing <em>Escherichia coli</em> (STEC) O113:H4 among human cases in Belgium questions the importance of this serotype as an emerging pathogen. However, detailed information focusing on serotype O113:H4 from human and non-human sources remains limited. We analysed a collection of 140 STEC O113:H4 isolates and their whole genomes, originating from animal hosts (cattle, deer, goats, and sheep), food, and humans, to determine their genetic relationship and assess key virulence genes. All STEC O113:H4 genomes lacked the locus of enterocyte effacement (LEE) and belonged to Pasteur Sequence Type (pST) 367 complex, dominated by pST367 (<em>ehxA</em><sup>-</sup>, <em>stx</em><sub>2d</sub><sup>+</sup>) and pST1729 (<em>ehxA</em><sup>+</sup>, <em>stx</em><sub>2b</sub><sup>+</sup>). Compared to <em>stx</em><sub>2d</sub><sup>+</sup> isolates, <em>stx</em><sub>2b</sub><sup>+</sup> isolates carried on median more virulence factors, which might thus contribute to enhanced pathogenicity. Besides, humans appear to be infected with distinct subgroups of STEC O113:H4 carrying distinct <em>stx</em> subtypes and originating from potentially different sources: deer, goats, and sheep for STEC carrying <em>stx</em><sub>2b</sub> (alone or in combination with <em>stx</em><sub>1c</sub>) and mainly cattle for STEC carrying <em>stx</em><sub>2d</sub>. Our results call for improved understanding and continuous surveillance of emerging STEC O113:H4.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151688"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acinetobacter baumannii (AB) is the most frequently isolated nosocomial pathogen, but severe infections by A. pittii, A. ursingii, and A. bereziniae are increasing. This study investigated the distribution and antibiotic resistance of Acinetobacter spp. strains from various clinical specimens.
Methods
Data were collected between 2021–2023 from clinical samples of hospitalized and outpatient individuals in southern Poland. Strains were identified using MALDI-TOF Biotyper, and antibiotic susceptibility was tested with the MIDITECH-Analyzer system. Statistical analyses were conducted using IBM SPSS Statistics.
Results
Among 1507 isolated Acinetobacter strains, 951 (63.1 %) were AB, while 556 (36.9 %) represented 27 non-AB species. Most isolates (73.6 %) came from outpatients, while 26.4 % were from hospitalized patients. A. ursingii (30.2 %), A. pittii (20.6 %), and A. junii (13 %) were the most common non-AB species. A. bereziniae, A. calcoaceticus, and A. proteolyticus were more frequently found in hospitalized patients. Non-AB species dominated in clinical specimens from genitourinary tract (87 %), whereas AB was more common in clinical specimens from invasive sites. Nearly all strains were non-susceptible to ciprofloxacin (98.4 %), with lower resistance rates to ampicillin/sulbactam (11.1 %), trimethoprim/sulfamethoxazole (5.8 %), gentamicin (2.9 %), amikacin (2.5 %), meropenem (1.6 %), and colistin (1.6 %). A. bereziniae showed frequently resistance to carbapenems, aminoglycosides, and trimethoprim/sulfamethoxazole. Colistin resistance was observed in A. ursingii and A. pittii.
Conclusions
While AB accounted for 63.1 % of isolates, non-AB species were common, particularly in clinical specimens from genitourinary tract and from skin and wound. Emerging hospital-acquired infections by species like A. pittii underline the need for vigilant monitoring. The high resistance to ciprofloxacin and low but noticeable resistance to carbapenems and colistin highlights the importance of early detection and resistance surveillance to prevent the spread of resistant strains.
{"title":"Distribution and antimicrobial resistance of Acinetobacter spp. isolated from different types of clinical specimens from hospitalized patients and outpatients in Poland","authors":"Tomasz Kasperski , Monika Pobiega , Monika Pomorska-Wesołowska , Wiktoria Papuga , Agnieszka Chmielarczyk","doi":"10.1016/j.ijmm.2025.151685","DOIUrl":"10.1016/j.ijmm.2025.151685","url":null,"abstract":"<div><h3>Background</h3><div><em>Acinetobacter baumannii</em> (AB) is the most frequently isolated nosocomial pathogen, but severe infections by <em>A. pittii</em>, <em>A. ursingii</em>, and <em>A. bereziniae</em> are increasing. This study investigated the distribution and antibiotic resistance of Acinetobacter spp. strains from various clinical specimens.</div></div><div><h3>Methods</h3><div>Data were collected between 2021–2023 from clinical samples of hospitalized and outpatient individuals in southern Poland. Strains were identified using MALDI-TOF Biotyper, and antibiotic susceptibility was tested with the MIDITECH-Analyzer system. Statistical analyses were conducted using IBM SPSS Statistics.</div></div><div><h3>Results</h3><div>Among 1507 isolated Acinetobacter strains, 951 (63.1 %) were AB, while 556 (36.9 %) represented 27 non-AB species. Most isolates (73.6 %) came from outpatients, while 26.4 % were from hospitalized patients. <em>A. ursingii</em> (30.2 %), <em>A. pittii</em> (20.6 %), and <em>A. junii</em> (13 %) were the most common non-AB species. <em>A. bereziniae</em>, <em>A. calcoaceticus</em>, and <em>A. proteolyticus</em> were more frequently found in hospitalized patients. Non-AB species dominated in clinical specimens from genitourinary tract (87 %), whereas AB was more common in clinical specimens from invasive sites. Nearly all strains were non-susceptible to ciprofloxacin (98.4 %), with lower resistance rates to ampicillin/sulbactam (11.1 %), trimethoprim/sulfamethoxazole (5.8 %), gentamicin (2.9 %), amikacin (2.5 %), meropenem (1.6 %), and colistin (1.6 %). <em>A. bereziniae</em> showed frequently resistance to carbapenems, aminoglycosides, and trimethoprim/sulfamethoxazole. Colistin resistance was observed in <em>A. ursingii</em> and <em>A. pittii</em>.</div></div><div><h3>Conclusions</h3><div>While AB accounted for 63.1 % of isolates, non-AB species were common, particularly in clinical specimens from genitourinary tract and from skin and wound. Emerging hospital-acquired infections by species like <em>A. pittii</em> underline the need for vigilant monitoring. The high resistance to ciprofloxacin and low but noticeable resistance to carbapenems and colistin highlights the importance of early detection and resistance surveillance to prevent the spread of resistant strains.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151685"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ijmm.2025.151691
Nicolas Heyer , Tobias Grebe , Andreas Schlattmann , Ahmed Mostafa Abdrabou , Jonel Trebicka , Frieder Schaumburg
Clostridioides difficile infection (CDI) is mediated by the cytotoxins TcdA and/or TcdB. The reliable detection of these toxins using enzyme immunoassays (EIA) could be affected by toxin stability. We assessed the toxin stability in stool samples spiked with TcdA or TcdB and in stool samples from CDI patients under transport conditions. In the spiked samples, the concentration of TcdB decreased faster than TcdA within 72 h. In contrast, toxin levels in stool samples from CDI patients remained stable within 24 h, while viable C. difficile slightly increased. In conclusion, toxin instability did not affect C. difficile toxin detection in our study.
{"title":"Stability of Clostridioides difficile toxins in stool samples","authors":"Nicolas Heyer , Tobias Grebe , Andreas Schlattmann , Ahmed Mostafa Abdrabou , Jonel Trebicka , Frieder Schaumburg","doi":"10.1016/j.ijmm.2025.151691","DOIUrl":"10.1016/j.ijmm.2025.151691","url":null,"abstract":"<div><div><em>Clostridioides difficile</em> infection (CDI) is mediated by the cytotoxins TcdA and/or TcdB. The reliable detection of these toxins using enzyme immunoassays (EIA) could be affected by toxin stability. We assessed the toxin stability in stool samples spiked with TcdA or TcdB and in stool samples from CDI patients under transport conditions. In the spiked samples, the concentration of TcdB decreased faster than TcdA within 72 h. In contrast, toxin levels in stool samples from CDI patients remained stable within 24 h, while viable <em>C. difficile</em> slightly increased. In conclusion, toxin instability did not affect <em>C. difficile</em> toxin detection in our study.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151691"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ijmm.2025.151687
Yutong Liu , Lin Wan , Xiong Li , Yingshun Zhou , Renjing Hu
<div><h3>Objective</h3><div>KL57 <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) is an emerging serotype with epidemiological characteristics and pathogenic mechanisms that remain incompletely understood. This study comprehensively analyzed the genomic features of KL57 <em>K. pneumoniae</em> strains isolated in Wuxi from 2016 to 2023, and investigated the global molecular epidemiology and population dynamics of KL57 <em>K. pneumoniae</em>.</div></div><div><h3>Methods</h3><div>From January 2016 to December 2023, 17 KL57 <em>K. pneumoniae</em> isolates were collected from various clinical specimens at the Wuxi No.2 People's Hospital, Jiangsu Province, China. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), and bioinformatics analysis including evaluation of virulence genes, resistance genes, and plasmid replicon types were performed on these strains. To elucidate the genetic relationships and global distribution of the KL57 <em>K. pneumoniae</em>, phylogenetic trees were constructed through comparative analyses of our KL57 strains alongside those obtained from public databases. Additionally, the distribution patterns of serotypes and carbapenemase genes among these strains were examined.</div></div><div><h3>Results</h3><div>Seventeen KL57 <em>K. pneumoniae</em> strains were categorized into four distinct sequence types (STs), with ST412 being the most prevalent in Wuxi, and ST2846, which was identified for the first time. Analysis of virulence genes indicated KL57 <em>K. pneumoniae</em> isolates often express multiple virulence factors. Antimicrobial resistance profiling revealed that only one ST218 isolate contained the <em>bla</em><sub>KPC-2</sub> gene, which was located on an IncFII<sub>K34</sub> plasmid. Geographically, ST412, ST218, and ST592 were the main predominant epidemic sequence types of the KL57 <em>K. pneumoniae</em>. A global analysis indicated that KL57 carbapenem-resistant <em>K. pneumoniae</em> (CRKp) strains predominantly harbored the <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>OXA-48</sub>, <em>bla</em><sub>KPC-2</sub>, and <em>bla</em><sub>OXA-181</sub> genes. Furthermore, phylogenetic analysis demonstrated significant diversity in the sequence types of KL57 <em>K. pneumoniae</em> strains across continents, with notable variations even between countries.</div></div><div><h3>Conclusion</h3><div>Our study corroborates the widespread occurrence of the ST412 KL57 <em>K. pneumoniae</em> in China and identifies a specific strain harboring the IncFII<sub>K34</sub> resistance plasmid. Additionally, the KL57 CRKp strain carries a variety of carbapenemase genes, and some of these strains simultaneously harbor multiple such genes. Our findings suggest that this subtype demonstrates enhanced resistance adaptability and may facilitate the dissemination of drug resistance through horizontal gene transfer. Consequently, it is necessary to develop more targeted surveillance strategies that focus on resistan
{"title":"Emergence of KL57 hypervirulent Klebsiella pneumoniae in Wuxi, China: Genomic insights into virulence plasmid evolution and blaKPC-2-bearing IncFIIK34 plasmid transmission","authors":"Yutong Liu , Lin Wan , Xiong Li , Yingshun Zhou , Renjing Hu","doi":"10.1016/j.ijmm.2025.151687","DOIUrl":"10.1016/j.ijmm.2025.151687","url":null,"abstract":"<div><h3>Objective</h3><div>KL57 <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) is an emerging serotype with epidemiological characteristics and pathogenic mechanisms that remain incompletely understood. This study comprehensively analyzed the genomic features of KL57 <em>K. pneumoniae</em> strains isolated in Wuxi from 2016 to 2023, and investigated the global molecular epidemiology and population dynamics of KL57 <em>K. pneumoniae</em>.</div></div><div><h3>Methods</h3><div>From January 2016 to December 2023, 17 KL57 <em>K. pneumoniae</em> isolates were collected from various clinical specimens at the Wuxi No.2 People's Hospital, Jiangsu Province, China. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), and bioinformatics analysis including evaluation of virulence genes, resistance genes, and plasmid replicon types were performed on these strains. To elucidate the genetic relationships and global distribution of the KL57 <em>K. pneumoniae</em>, phylogenetic trees were constructed through comparative analyses of our KL57 strains alongside those obtained from public databases. Additionally, the distribution patterns of serotypes and carbapenemase genes among these strains were examined.</div></div><div><h3>Results</h3><div>Seventeen KL57 <em>K. pneumoniae</em> strains were categorized into four distinct sequence types (STs), with ST412 being the most prevalent in Wuxi, and ST2846, which was identified for the first time. Analysis of virulence genes indicated KL57 <em>K. pneumoniae</em> isolates often express multiple virulence factors. Antimicrobial resistance profiling revealed that only one ST218 isolate contained the <em>bla</em><sub>KPC-2</sub> gene, which was located on an IncFII<sub>K34</sub> plasmid. Geographically, ST412, ST218, and ST592 were the main predominant epidemic sequence types of the KL57 <em>K. pneumoniae</em>. A global analysis indicated that KL57 carbapenem-resistant <em>K. pneumoniae</em> (CRKp) strains predominantly harbored the <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>OXA-48</sub>, <em>bla</em><sub>KPC-2</sub>, and <em>bla</em><sub>OXA-181</sub> genes. Furthermore, phylogenetic analysis demonstrated significant diversity in the sequence types of KL57 <em>K. pneumoniae</em> strains across continents, with notable variations even between countries.</div></div><div><h3>Conclusion</h3><div>Our study corroborates the widespread occurrence of the ST412 KL57 <em>K. pneumoniae</em> in China and identifies a specific strain harboring the IncFII<sub>K34</sub> resistance plasmid. Additionally, the KL57 CRKp strain carries a variety of carbapenemase genes, and some of these strains simultaneously harbor multiple such genes. Our findings suggest that this subtype demonstrates enhanced resistance adaptability and may facilitate the dissemination of drug resistance through horizontal gene transfer. Consequently, it is necessary to develop more targeted surveillance strategies that focus on resistan","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151687"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}