Pub Date : 2026-06-01Epub 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":"2026-06-01","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 : 2026-06-01Epub Date: 2026-01-31DOI: 10.1016/j.ijmm.2026.151705
Sika Dossim , Komla M. Dossouvi , Amivi M. Godonou , Essokedi Tchedie , Mounerou Salou , Anoumou Y. Dagnra , Thierry Naas
Genomics have become crucial in addressing the public health challenges posed by antimicrobial resistance (AMR). In this study, we performed the first whole-genome sequencing (WGS) and genomic analyses of clinical Acinetobacter baumannii (A. baumannii) strains isolated at the Sylvanus Olympio University Teaching Hospital in Lomé, Togo. This prospective study, conducted from April 19 to September 02, 2019. Susceptibility profiles were obtained using the Kirby-Bauer disc diffusion method, and the nine studied carbapenem-resistant A. baumannii strains were subjected to next generation sequencing (NGS) using an Illumina platform. All isolates exhibited resistance to imipenem, ticarcillin, clavulanic acid, cefotaxime, and ciprofloxacin, but remained susceptible to colistin, tigecycline, and rifampicin. The study identified five A. baumannii ST1 strains, two ST103 strains, one ST52 strain, and one ST1153 strain. The number of AMR genes per strain ranged from six to 24, whereas the number of virulence genes per strain varied from 32 to 67. Each isolate contained at least one plasmid, with the number of plasmids per isolate ranging from one to four per isolate. The carbapenemase-producing genes blaOXA-23, blaOXA-58, blaOXA-68, blaOXA-69, blaOXA-70, blaOXA-91, and blaNDM-1 were identified, along with blaCTX-M-15 and other antibiotic resistance genes. Additionally, multidrug efflux system genes, including adeCFGHIJKLMNS, abeSJ, and amvA, and a wide array of virulence and biofilm-forming genetic determinants were found in all isolates. Eleven integrons were detected, featuring aac(3)-Ia, sat-2, and dfrA1 cassettes. Tn6018, carrying the mercury resistance gene merR and czcD (Co/Zn/Cd efflux system), and Tn2007, carrying blaOXA-23, were present in six genomes. Four Ghanaian genomes were most closely related to the A. baumannii ST1 and ST103 strains reported in this study. Furthermore, several multidrug resistance plasmids and one virulence and AMR hybrid plasmid (accession number JBFMWK020002174.1) were identified. This study provides valuable insights into clinical A. baumannii in Togo, underscoring the need for more frequent genomic studies in sub-Saharan countries to effectively monitor and combat AMR in Africa.
{"title":"Resistome, virulome and mobilome of clinical carbapenemase-producing Acinetobacter baumannii strains isolated in Togo","authors":"Sika Dossim , Komla M. Dossouvi , Amivi M. Godonou , Essokedi Tchedie , Mounerou Salou , Anoumou Y. Dagnra , Thierry Naas","doi":"10.1016/j.ijmm.2026.151705","DOIUrl":"10.1016/j.ijmm.2026.151705","url":null,"abstract":"<div><div>Genomics have become crucial in addressing the public health challenges posed by antimicrobial resistance (AMR). In this study, we performed the first whole-genome sequencing (WGS) and genomic analyses of clinical <em>Acinetobacter baumannii</em> (<em>A. baumannii</em>) strains isolated at the Sylvanus Olympio University Teaching Hospital in Lomé, Togo. This prospective study, conducted from April 19 to September 02, 2019. Susceptibility profiles were obtained using the Kirby-Bauer disc diffusion method, and the nine studied carbapenem-resistant <em>A. baumannii</em> strains were subjected to next generation sequencing (NGS) using an <em>Illumina</em> platform. All isolates exhibited resistance to imipenem, ticarcillin, clavulanic acid, cefotaxime, and ciprofloxacin, but remained susceptible to colistin, tigecycline, and rifampicin. The study identified five <em>A. baumannii</em> ST1 strains, two ST103 strains, one ST52 strain, and one ST1153 strain. The number of AMR genes per strain ranged from six to 24, whereas the number of virulence genes per strain varied from 32 to 67. Each isolate contained at least one plasmid, with the number of plasmids per isolate ranging from one to four per isolate. The carbapenemase-producing genes <em>bla</em><sub>OXA-23</sub>, <em>bla</em><sub>OXA-58</sub>, <em>bla</em><sub>OXA-68</sub>, <em>bla</em><sub>OXA-69</sub>, <em>bla</em><sub>OXA-70</sub>, <em>bla</em><sub>OXA-91</sub>, and <em>bla</em><sub>NDM-1</sub> were identified, along with <em>bla</em><sub>CTX-M-15</sub> and other antibiotic resistance genes. Additionally, multidrug efflux system genes, including <em>ade</em>CFGHIJKLMNS, <em>abe</em>SJ, and <em>amv</em>A, and a wide array of virulence and biofilm-forming genetic determinants were found in all isolates. Eleven integrons were detected, featuring <em>aac(3)-Ia</em>, <em>sat-</em>2, and <em>dfr</em>A1 cassettes. Tn<em>6018</em>, carrying the mercury resistance gene <em>mer</em>R and <em>czc</em>D (Co/Zn/Cd efflux system), and Tn<em>2007</em>, carrying <em>bla</em><sub>OXA-23</sub>, were present in six genomes. Four Ghanaian genomes were most closely related to the <em>A. baumannii</em> ST1 and ST103 strains reported in this study. Furthermore, several multidrug resistance plasmids and one virulence and AMR hybrid plasmid (accession number JBFMWK020002174.1) were identified. This study provides valuable insights into clinical <em>A. baumannii</em> in Togo, underscoring the need for more frequent genomic studies in sub-Saharan countries to effectively monitor and combat AMR in Africa.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151705"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120298","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 : 2026-06-01Epub Date: 2025-12-16DOI: 10.1016/j.ijmm.2025.151690
Domonkos Sváb , Linda Falgenhauer , Eszter Kotogán , Trinad Chakraborty , István Tóth
Cytolethal distending toxin (CDT), a cyclomodulin and genotoxin produced by many Gram-negative bacteria including pathogenic Escherichia coli, disrupts the eukaryotic host cell cycle to facilitate bacterial colonization. In a survey of dairy cows in Hungary, 7 % of of sampled animal and farm environment isolates carried CDT-producing E. coli (CTEC). Whole genome sequencing (WGS) performed on six recent isolates and three historical CTEC strains revealed association with diverse pathotypes, including enteropathogenic- (EPEC) and necrotoxigenic- (NTEC) types, as well as several unclassified atypical strains. Four of the six strains isolated in this study carried plasmid encoding cdt-III+ NTEC, while a prophage based cdt-V allele was present in the remaining two strains which were of unknown pathotype. These isolates exhibited significant variability in their supplementary virulence genes (SVGs) content as well as in multiple prophage regions linked to virulence or fitness factors. They were phylogenetically distinct and comprised of only distantly related sequence types (STs) that include two novel STs. Several isolates also carried other genotoxic cyclomodulins such as the cytotoxic necrotizing factor (cnf), the cycle inhibiting factor (cif), and colibactin (polyketide synthase, pks) which is located on a genomic island, indicating multiple mechanisms for dysplastic damage of the eukaryotic host cells exist and highlight the role of horizontal gene transfer in the zoonotic and pathogenic potential of CTEC.
{"title":"Comparative genomic analysis of cyclomodulin-producing Escherichia coli strains of animal origin","authors":"Domonkos Sváb , Linda Falgenhauer , Eszter Kotogán , Trinad Chakraborty , István Tóth","doi":"10.1016/j.ijmm.2025.151690","DOIUrl":"10.1016/j.ijmm.2025.151690","url":null,"abstract":"<div><div>Cytolethal distending toxin (CDT), a cyclomodulin and genotoxin produced by many Gram-negative bacteria including pathogenic <em>Escherichia coli</em>, disrupts the eukaryotic host cell cycle to facilitate bacterial colonization. In a survey of dairy cows in Hungary, 7 % of of sampled animal and farm environment isolates carried CDT-producing <em>E. coli</em> (CTEC). Whole genome sequencing (WGS) performed on six recent isolates and three historical CTEC strains revealed association with diverse pathotypes, including enteropathogenic- (EPEC) and necrotoxigenic- (NTEC) types, as well as several unclassified atypical strains. Four of the six strains isolated in this study carried plasmid encoding <em>cdt-III+</em> NTEC, while a prophage based <em>cdt-V</em> allele was present in the remaining two strains which were of unknown pathotype. These isolates exhibited significant variability in their supplementary virulence genes (SVGs) content as well as in multiple prophage regions linked to virulence or fitness factors. They were phylogenetically distinct and comprised of only distantly related sequence types (STs) that include two novel STs. Several isolates also carried other genotoxic cyclomodulins such as the cytotoxic necrotizing factor (<em>cnf</em>), the cycle inhibiting factor (<em>cif</em>), and colibactin (polyketide synthase, <em>pks</em>) which is located on a genomic island, indicating multiple mechanisms for dysplastic damage of the eukaryotic host cells exist and highlight the role of horizontal gene transfer in the zoonotic and pathogenic potential of CTEC.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151690"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913863","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 : 2026-06-01Epub Date: 2026-01-12DOI: 10.1016/j.ijmm.2026.151700
Hajnalka Juhász , Katalin Burián , Mátyás Bukva , Gabriella Terhes
Our study determined the prevalence, types of RSV, and sequence variability of the G and F genes in Hungary between 2017 and 2023. During the study, 1828 respiratory samples were collected from hospitalised pediatric patients. We confirmed the presence of RSV A in 12.74 %, RSV B in 13.85 %, and their simultaneous presence in 0.27 %. The highest RSV positivity was observed in the 2018–2019 season, while the lowest was in the 2017–2018 season. Following the SARS-CoV-2 pandemic, the RSV season has an earlier onset and longer duration than it did previously; however, an earlier onset was already detected in 2018. All RSV A isolates are classified into the A.D., while RSV B into the B.D. clades. The entire ectodomain of G protein showed a high sequence diversity, higher than in the case of B.D. strains. Mutations at position 276, adjacent to the palivizumab binding site of the F protein, could be detected. At the same time, neither K272E/N nor any other mutation is present in the palivizumab binding region in our strains. Several mutations in the nirsevimab binding region could be detected in our strains; however, none of these mutations, which would affect nirsevimab activity, were found in our isolates.
{"title":"Sequence variability of Hungarian RSV G and F proteins between 2017 and 2023: single-center study","authors":"Hajnalka Juhász , Katalin Burián , Mátyás Bukva , Gabriella Terhes","doi":"10.1016/j.ijmm.2026.151700","DOIUrl":"10.1016/j.ijmm.2026.151700","url":null,"abstract":"<div><div>Our study determined the prevalence, types of RSV, and sequence variability of the G and F genes in Hungary between 2017 and 2023. During the study, 1828 respiratory samples were collected from hospitalised pediatric patients. We confirmed the presence of RSV A in 12.74 %, RSV B in 13.85 %, and their simultaneous presence in 0.27 %. The highest RSV positivity was observed in the 2018–2019 season, while the lowest was in the 2017–2018 season. Following the SARS-CoV-2 pandemic, the RSV season has an earlier onset and longer duration than it did previously; however, an earlier onset was already detected in 2018. All RSV A isolates are classified into the A.D., while RSV B into the B.D. clades. The entire ectodomain of G protein showed a high sequence diversity, higher than in the case of B.D. strains. Mutations at position 276, adjacent to the palivizumab binding site of the F protein, could be detected. At the same time, neither K272E/N nor any other mutation is present in the palivizumab binding region in our strains. Several mutations in the nirsevimab binding region could be detected in our strains; however, none of these mutations, which would affect nirsevimab activity, were found in our isolates.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151700"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977643","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 : 2026-06-01Epub Date: 2025-12-23DOI: 10.1016/j.ijmm.2025.151698
Raphael Hermann , Annika Sobkowiak , Franziska Schuler , Vincent van Almsick , Alexander Mellmann , Vera Schwierzeck
Our study characterized 301 extended-spectrum beta-lactamases (ESBL) Escherichia coli isolates collected a tertiary hospital in Germany during a during an 18-month period starting from March 2021. All isolates were subjected to long-read whole genome sequencing (lrWGS) to identify resistance genes, type strains and investigate genetic relatedness. Results showed that the sequence type (ST)131 subclade B2 dominates the E. coli population. While carbapenemase genes were rare (n = 7), the most common resistance genes identified were the extended-spectrum beta-lactamase (ESBL) encoding genes blaCTX-M-15 (26.6 %), blaCTX-M-27 (18.9 %) and blaOXA-1 in combination with blaCTX-M-15 (14.6 %). About half of the isolates were categorized as nosocomial. Epidemiological evaluation and genetic analysis of bacterial isolates identified five probable cases of transmission during hospital admission. 43,7 % (55 isolates) of the E. coli ST131 isolates were detected in urine samples. 23 % of respective patients received antibiotic treatment prior to sample collection. Moreover, we used lrWGS data to investigate the antimicrobial resistance plasmids in the E. coli ST131 isolates. In total, 68 E. coli ST131 carried at least one ESBL gene on a plasmid. Of these, the blaCTX-M-27 carrying IncF plasmid was detected in 49 isolates. Taken together our study represents a detailed characterization of the ESBL E. coli population in the hospital setting and highlights the role of ST131 E. coli for hospital epidemiology.
{"title":"Epidemiology of multidrug resistant E. coli isolates from a German university hospital illustrates dominance of E. coli ST131","authors":"Raphael Hermann , Annika Sobkowiak , Franziska Schuler , Vincent van Almsick , Alexander Mellmann , Vera Schwierzeck","doi":"10.1016/j.ijmm.2025.151698","DOIUrl":"10.1016/j.ijmm.2025.151698","url":null,"abstract":"<div><div>Our study characterized 301 extended-spectrum beta-lactamases (ESBL) <em>Escherichia coli</em> isolates collected a tertiary hospital in Germany during a during an 18-month period starting from March 2021. All isolates were subjected to long-read whole genome sequencing (lrWGS) to identify resistance genes, type strains and investigate genetic relatedness. Results showed that the sequence type (ST)131 subclade B2 dominates the <em>E. coli</em> population. While carbapenemase genes were rare (n = 7), the most common resistance genes identified were the extended-spectrum beta-lactamase (ESBL) encoding genes <em>bla</em><sub>CTX-M-15</sub> (26.6 %), <em>bla</em><sub>CTX-M-27</sub> (18.9 %) and <em>bla</em><sub>OXA-1</sub> in combination with <em>bla</em><sub>CTX-M-15</sub> (14.6 %)<em>.</em> About half of the isolates were categorized as nosocomial. Epidemiological evaluation and genetic analysis of bacterial isolates identified five probable cases of transmission during hospital admission. 43,7 % (55 isolates) of the <em>E. coli</em> ST131 isolates were detected in urine samples. 23 % of respective patients received antibiotic treatment prior to sample collection. Moreover, we used lrWGS data to investigate the antimicrobial resistance plasmids in the <em>E. coli</em> ST131 isolates. In total, 68 <em>E. coli</em> ST131 carried at least one ESBL gene on a plasmid. Of these, the <em>bla</em><sub>CTX-M-27</sub> carrying <em>IncF</em> plasmid was detected in 49 isolates. Taken together our study represents a detailed characterization of the ESBL <em>E. coli</em> population in the hospital setting and highlights the role of ST131 <em>E. coli</em> for hospital epidemiology.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151698"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913841","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 : 2026-06-01Epub Date: 2026-02-10DOI: 10.1016/j.ijmm.2026.151707
Mei Li, Zeqing Xu, Jiarui Zeng, Xiaoqi Zhang, Shixuan Chen, Zhaonan Shen, Yixuan Wu, Wenli Liu, Ziqiang Pan
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key genes in Koi Carp responding to S. aureus from human rhinitis remain unclear. In this study, we established an intraperitoneal infection model in koi carp (Cyprinus carpio) using an S. aureus isolate from patients with rhinitis and integrated RNA-seq, qPCR, and ELISA to dissect the host response. Our findings reveal a dual-module immune evasion strategy employed by S. aureus in koi carp. Module I: The pathogen down-regulated the entire complement coagulation cascade (C3, C9, CFH, F7/9/10) and apolipoprotein-mediated opsonins (APOA1, APOB, APOC1/2), thereby crippling innate clearance. Module II: The host mounted a restricted but potent counter-response, characterized by type I IFN signalling (gvin1, MHC-I), NK/T-cell co-stimulation (CD244, SLAMF5), and the selective induction of IL-8 and IL-1β, while IL-6, IL-10, and TNF-α remained unchanged. Functionally, serum superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM) activities surged, confirming an oxidative burst, whereas splenic CD22R protein decreased, indicating B-cell disinhibition. These results establish a molecular basis for understanding the interaction between human-derived S. aureus and the immune system of aquatic organisms.
{"title":"Transcriptomic and functional evidence reveals dual-module immune response of human-nasal staphylococcus aureus in Koi Carp (Cyprinus carpio)","authors":"Mei Li, Zeqing Xu, Jiarui Zeng, Xiaoqi Zhang, Shixuan Chen, Zhaonan Shen, Yixuan Wu, Wenli Liu, Ziqiang Pan","doi":"10.1016/j.ijmm.2026.151707","DOIUrl":"10.1016/j.ijmm.2026.151707","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key genes in Koi Carp responding to <em>S. aureus</em> from human rhinitis remain unclear. In this study, we established an intraperitoneal infection model in koi carp (<em>Cyprinus carpio</em>) using an <em>S. aureus</em> isolate from patients with rhinitis and integrated RNA-seq, qPCR, and ELISA to dissect the host response. Our findings reveal a dual-module immune evasion strategy employed by <em>S. aureus</em> in koi carp. Module I: The pathogen down-regulated the entire complement coagulation cascade (C3, C9, CFH, F7/9/10) and apolipoprotein-mediated opsonins (APOA1, APOB, APOC1/2), thereby crippling innate clearance. Module II: The host mounted a restricted but potent counter-response, characterized by type I IFN signalling (gvin1, MHC-I), NK/T-cell co-stimulation (CD244, SLAMF5), and the selective induction of IL-8 and IL-1β, while IL-6, IL-10, and TNF-α remained unchanged. Functionally, serum superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM) activities surged, confirming an oxidative burst, whereas splenic CD22R protein decreased, indicating B-cell disinhibition. These results establish a molecular basis for understanding the interaction between human-derived <em>S. aureus</em> and the immune system of aquatic organisms.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"322 ","pages":"Article 151707"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188592","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}
Enteroinvasive Escherichia coli (EIEC) is a diarrhoeagenic E. coli pathotype that shares key virulence traits with Shigella, including the invasion plasmid (pINV). In Thailand, an outbreak caused by the EIEC serotype O8:H19—the first reported in the country—occurred in 2023, affecting over 150 patients. To elucidate the emergence, clinical relevance, and epidemiological distribution of EIEC in Thailand, we conducted a comprehensive investigation. We isolated and genomically characterised 63 isolates, comprising 28 EIEC (eight serotypes, including O96:H19 from a 2024 outbreak) and 35 Shigella (25 S. sonnei and 10 S. flexneri), along with 85 global reference strains. Comparative genomics revealed that the 2023 and 2024 EIEC outbreak isolates, along with a novel OX18:H25 EIEC lineage, harboured highly similar pINV plasmids with conserved invasion genes and complete conjugation elements. These isolates retained several biochemical traits that were more typical of commensal E. coli than classical EIEC. Limited chromosomal genome reduction—a hallmark of Shigella— was observed, which suggests that these lineages are in an early stage of adaptation toward a pathogenic lifestyle. Phylogenomic analysis showed that OX18:H25 is closely related to livestock-associated E. coli, supporting the hypothesis that pINV was recently acquired via horizontal gene transfer. These findings highlight the active circulation of putatively conjugative virulence plasmids among E. coli populations and the ongoing emergence of novel EIEC clones with epidemic-inducing potential.
{"title":"Genomic analyses of enteroinvasive Escherichia coli revealed the circulation of conjugative virulence plasmids and emergence of novel clones","authors":"Kazuhisa Okada , Warawan Wongboot , Amonrattana Roobthaisong , Nonzee Hanchanachai , Pawinee Doung-ngern , Pilailuk Akkapaiboon Okada , Thanee Wongchai , Witaya Swaddiwudhipong , Tetsuya Iida , Shigeyuki Hamada","doi":"10.1016/j.ijmm.2025.151677","DOIUrl":"10.1016/j.ijmm.2025.151677","url":null,"abstract":"<div><div>Enteroinvasive <em>Escherichia coli</em> (EIEC) is a diarrhoeagenic <em>E. coli</em> pathotype that shares key virulence traits with <em>Shigella</em>, including the invasion plasmid (pINV). In Thailand, an outbreak caused by the EIEC serotype O8:H19—the first reported in the country—occurred in 2023, affecting over 150 patients. To elucidate the emergence, clinical relevance, and epidemiological distribution of EIEC in Thailand, we conducted a comprehensive investigation. We isolated and genomically characterised 63 isolates, comprising 28 EIEC (eight serotypes, including O96:H19 from a 2024 outbreak) and 35 <em>Shigella</em> (25 <em>S. sonnei</em> and 10 <em>S. flexneri</em>), along with 85 global reference strains. Comparative genomics revealed that the 2023 and 2024 EIEC outbreak isolates, along with a novel OX18:H25 EIEC lineage, harboured highly similar pINV plasmids with conserved invasion genes and complete conjugation elements. These isolates retained several biochemical traits that were more typical of commensal <em>E. coli</em> than classical EIEC. Limited chromosomal genome reduction—a hallmark of <em>Shigella</em>— was observed, which suggests that these lineages are in an early stage of adaptation toward a pathogenic lifestyle. Phylogenomic analysis showed that OX18:H25 is closely related to livestock-associated <em>E. coli</em>, supporting the hypothesis that pINV was recently acquired via horizontal gene transfer. These findings highlight the active circulation of putatively conjugative virulence plasmids among <em>E. coli</em> populations and the ongoing emergence of novel EIEC clones with epidemic-inducing potential.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151677"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158885","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 : 2025-12-01Epub Date: 2025-09-21DOI: 10.1016/j.ijmm.2025.151675
Deng Hui , Zhu Bin , Zhang Shiyu , Zhang Bin , Dilihumar Zaire , Gao Ruihan , Liu Shuting , Zhou Xin , Zhou Shunchang , Xiong Jian , Yang Xuecheng , Feng Xuemei , Lu Yinping , Zheng Xin , Wang Baoju
Hepatitis B virus (HBV) infection seems to be related to gut microbiota. This study aims to explore the effects of HBV infection on gut microbiota and possible immunological mechanisms using the Chinese woodchuck model. Nine adult woodchucks were randomly divided into Cyclosporine A (CsA) or Control group. Animals were orally treated with CsA and saline for 2 weeks before WHV inoculation, and continued until 8 weeks after that. Blood CsA concentrations were tested at 2 weeks after administration and before discontinuation. Quantitative PCR was used to detect serum WHV DNA. Flow cytometry was used to detect T cell immune response. Feces were collected for 16S rRNA sequencing. The result shows CsA oral administration can reach effective blood drug concentration in woodchucks and successfully prolong WHV replication. After 2 weeks of oral treatment, there was no significant difference in the gut microbiota between the two groups. At the clearance period of serum WHV, the relative abundance of Prevotella and Prevotella genera in the phylum Bacteroidetes significantly increased, while the relative abundance of Firmicutes significantly decreased. Meanwhile, the CD107a degranulation of CD4-T cells in peripheral blood showed a decreasing trend, while there was no significant difference in the frequency of PD-1+ CD4-T cells. In Conclusion, oral administration of CsA can significantly prolong the replication time of WHV in Chinese woodchucks. The gut microbiota of Chinese woodchuck undergoes significant changes during serum WHV clearance, which implies the Chinese woodchuck model can be used to study the interaction between HBV infection and gut microbiota.
{"title":"The impact of HBV infection on gut microbiota using Chinese woodchuck model with woodchuck hepatitis virus (WHV) infection","authors":"Deng Hui , Zhu Bin , Zhang Shiyu , Zhang Bin , Dilihumar Zaire , Gao Ruihan , Liu Shuting , Zhou Xin , Zhou Shunchang , Xiong Jian , Yang Xuecheng , Feng Xuemei , Lu Yinping , Zheng Xin , Wang Baoju","doi":"10.1016/j.ijmm.2025.151675","DOIUrl":"10.1016/j.ijmm.2025.151675","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) infection seems to be related to gut microbiota. This study aims to explore the effects of HBV infection on gut microbiota and possible immunological mechanisms using the Chinese woodchuck model. Nine adult woodchucks were randomly divided into Cyclosporine A (CsA) or Control group. Animals were orally treated with CsA and saline for 2 weeks before WHV inoculation, and continued until 8 weeks after that. Blood CsA concentrations were tested at 2 weeks after administration and before discontinuation. Quantitative PCR was used to detect serum WHV DNA. Flow cytometry was used to detect T cell immune response. Feces were collected for 16S rRNA sequencing. The result shows CsA oral administration can reach effective blood drug concentration in woodchucks and successfully prolong WHV replication. After 2 weeks of oral treatment, there was no significant difference in the gut microbiota between the two groups. At the clearance period of serum WHV, the relative abundance of Prevotella and Prevotella genera in the phylum Bacteroidetes significantly increased, while the relative abundance of Firmicutes significantly decreased. Meanwhile, the CD107a degranulation of CD4-T cells in peripheral blood showed a decreasing trend, while there was no significant difference in the frequency of PD-1+ CD4-T cells. In Conclusion, oral administration of CsA can significantly prolong the replication time of WHV in Chinese woodchucks. The gut microbiota of Chinese woodchuck undergoes significant changes during serum WHV clearance, which implies the Chinese woodchuck model can be used to study the interaction between HBV infection and gut microbiota.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151675"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119465","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 : 2025-12-01Epub Date: 2025-09-20DOI: 10.1016/j.ijmm.2025.151678
Cheng-Yen Kao , Nevia Longjam , Jazon Harl Hidrosollo , Lee-Chung Lin , Jang-Jih Lu
Staphylococcus lugdunensis, an emerging coagulase-negative Staphylococcus (CoNS) pathogen, has garnered increasing interest due to its production of lugdunin, a thiazolidine-containing antimicrobial peptide. However, standardized protocols for directly assessing lugdunin activity produced by S. lugdunensis remain lacking. In this study, we examined the effects of pH and incubation duration on lugdunin activity and evaluated the antibacterial spectrum of lugdunin produced by S. lugdunensis isolates against a panel of gram-positive and gram-negative bacterial strains. The optimal conditions for lugdunin antibacterial activity of isolate CGMH-SL85 were identified as pH 7.5 and a 72-h incubation period. Under the tested conditions, the lugdunin produced by CGMH-SL85 exhibited antimicrobial activity against five gram-positive strains, including Staphylococcus aureus ATCC29213 and Staphylococcus haemolyticus CGMH-SH53, followed by Enterococcus faecium EF029 and EF081–2 and Listeria monocytogenes ATCC10403S. However, no antibacterial activity was observed against any of the 11 tested gram-negative bacterial species. Furthermore, four distinct lugdunin susceptibility phenotypes were observed among 47 lugdunin-nonproducing S. lugdunensis strains (14 sequence type (ST)4, 27 ST27, and 6 ST29 strains), including Type A characterized by large, clear inhibition zones; Type B with smaller, clear zones; Type C displaying halo-like inhibition zones; and Type D showing no detectable activity. Moreover, 20 S. lugdunensis strains (42.6 %) exhibited the Type C phenotype. Notably, all six ST29 strains displayed the Type C phenotype, while the Type A phenotype was observed only among ST27 strains (3 strains). In conclusion, we developed a standardized protocol for evaluating lugdunin activity, using pH 7.5 and a 72-h incubation period, and found that different S. lugdunensis strains exhibited distinct lugdunin susceptibility phenotypes.
{"title":"Optimization and spectrum characterization of the antibacterial activity of lugdunin","authors":"Cheng-Yen Kao , Nevia Longjam , Jazon Harl Hidrosollo , Lee-Chung Lin , Jang-Jih Lu","doi":"10.1016/j.ijmm.2025.151678","DOIUrl":"10.1016/j.ijmm.2025.151678","url":null,"abstract":"<div><div><em>Staphylococcus lugdunensis</em>, an emerging coagulase-negative <em>Staphylococcus</em> (CoNS) pathogen, has garnered increasing interest due to its production of lugdunin, a thiazolidine-containing antimicrobial peptide. However, standardized protocols for directly assessing lugdunin activity produced by <em>S. lugdunensis</em> remain lacking. In this study, we examined the effects of pH and incubation duration on lugdunin activity and evaluated the antibacterial spectrum of lugdunin produced by <em>S. lugdunensis</em> isolates against a panel of gram-positive and gram-negative bacterial strains. The optimal conditions for lugdunin antibacterial activity of isolate CGMH-SL85 were identified as pH 7.5 and a 72-h incubation period. Under the tested conditions, the lugdunin produced by CGMH-SL85 exhibited antimicrobial activity against five gram-positive strains, including <em>Staphylococcus aureus</em> ATCC29213 and <em>Staphylococcus haemolyticus</em> CGMH-SH53, followed by <em>Enterococcus faecium</em> EF029 and EF081–2 and <em>Listeria monocytogenes</em> ATCC10403S. However, no antibacterial activity was observed against any of the 11 tested gram-negative bacterial species. Furthermore, four distinct lugdunin susceptibility phenotypes were observed among 47 lugdunin-nonproducing <em>S. lugdunensis</em> strains (14 sequence type (ST)4, 27 ST27, and 6 ST29 strains), including Type A characterized by large, clear inhibition zones; Type B with smaller, clear zones; Type C displaying halo-like inhibition zones; and Type D showing no detectable activity. Moreover, 20 <em>S. lugdunensis</em> strains (42.6 %) exhibited the Type C phenotype. Notably, all six ST29 strains displayed the Type C phenotype, while the Type A phenotype was observed only among ST27 strains (3 strains). In conclusion, we developed a standardized protocol for evaluating lugdunin activity, using pH 7.5 and a 72-h incubation period, and found that different <em>S. lugdunensis</em> strains exhibited distinct lugdunin susceptibility phenotypes.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151678"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119466","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 : 2025-12-01Epub Date: 2025-10-15DOI: 10.1016/j.ijmm.2025.151679
Shereen O. Abd Algaffar , Annelies Verbon , Kimberly Eadie , Deborah Horst-Kreft , Sami A. Khalid , Wendy W.J. van de Sande
Mycetoma is a neglected tropical disease characterized by large tumorous lesions. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). The hallmark of mycetoma is the formation of grains by the causative agent. Grains can only be formed in vivo; therefore, in vivo models are crucial to studying mycetoma. In vivo, grain models have been developed in the invertebrate Galleria mellonella for eumycetoma, but not for actinomycetoma. Here, we aimed to develop the first actinomycetoma grain model in G. mellonella larvae. Actinomadura madurae strains DSM43236 and DSM44005 were used to infect G. mellonella larvae. Larval survival was monitored over 10 days. Grain formation was studied histologically and compared to grains in human tissues. The efficacy of trimethoprim-sulfamethoxazole and amikacin, the current standard treatment for actinomycetoma, was determined. A. madurae infection decreased the survival of G. mellonella larvae in a concentration-dependent manner. Grains were formed within 24 h post-infection. After 72 h these grains became melanised. No significantly enhanced survival was noted with trimethoprim-sulfamethoxazole, amikacin, or a combination thereof. In this model, the melanised A. madurae grains did differ from human grains, most likely due to the immune system of G. mellonella. The lack of therapeutic efficacy could be caused by this melanin or the fact that A. madurae grains, in general, are less susceptible to these drugs. More research will be needed to address this question.
{"title":"The development of an Actinomadura madurae grain model in Galleria mellonella larvae","authors":"Shereen O. Abd Algaffar , Annelies Verbon , Kimberly Eadie , Deborah Horst-Kreft , Sami A. Khalid , Wendy W.J. van de Sande","doi":"10.1016/j.ijmm.2025.151679","DOIUrl":"10.1016/j.ijmm.2025.151679","url":null,"abstract":"<div><div>Mycetoma is a neglected tropical disease characterized by large tumorous lesions. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). The hallmark of mycetoma is the formation of grains by the causative agent. Grains can only be formed <em>in vivo;</em> therefore, <em>in vivo</em> models are crucial to studying mycetoma<em>. In vivo,</em> grain models have been developed in the invertebrate <em>Galleria mellonella</em> for eumycetoma, but not for actinomycetoma. Here, we aimed to develop the first actinomycetoma grain model in <em>G. mellonella</em> larvae. <em>Actinomadura madurae</em> strains DSM43236 and DSM44005 were used to infect <em>G. mellonella</em> larvae. Larval survival was monitored over 10 days. Grain formation was studied histologically and compared to grains in human tissues. The efficacy of trimethoprim-sulfamethoxazole and amikacin, the current standard treatment for actinomycetoma, was determined. <em>A. madurae</em> infection decreased the survival of <em>G. mellonella</em> larvae in a concentration-dependent manner. Grains were formed within 24 h post-infection. After 72 h these grains became melanised. No significantly enhanced survival was noted with trimethoprim-sulfamethoxazole, amikacin, or a combination thereof. In this model, the melanised <em>A. madurae</em> grains did differ from human grains, most likely due to the immune system of <em>G. mellonella</em>. The lack of therapeutic efficacy could be caused by this melanin or the fact that <em>A. madurae</em> grains, in general, are less susceptible to these drugs. More research will be needed to address this question.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151679"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318953","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}
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