Journal of medical microbiology最新文献

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Rabbit intradermal inoculations as an efficient method to quantitate Treponema pallidum. 兔皮内接种作为梅毒螺旋体定量的有效方法。
IF 2
Journal of medical microbiology Pub Date : 2026-09-01 DOI: 10.1099/jmm.0.002199
Oksana Yakovleva, Teresa Pilant, Juraj Cervenak, R Damaris Molano, Luisa Gregori
{"title":"Rabbit intradermal inoculations as an efficient method to quantitate <i>Treponema pallidum</i>.","authors":"Oksana Yakovleva, Teresa Pilant, Juraj Cervenak, R Damaris Molano, Luisa Gregori","doi":"10.1099/jmm.0.002199","DOIUrl":"10.1099/jmm.0.002199","url":null,"abstract":"<p><p><b>Background</b>. Histological examination and rabbit intratesticular inoculation of clinical specimens are traditionally used to diagnose syphilis and characterize the aetiological agent, <i>Treponema pallidum</i>. Usually, these methods provide only qualitative data of the bacterium. For quantitative analysis, dark-field microscopy and real-time PCR are commonly used but both methods have important limitations. We investigated intradermal inoculations in rabbits as a sensitive and quantitative alternative test method.<b>Methods</b>. We prepared 10-fold serial dilutions of a treponemal stock ranging from 4×10³ to 4 treponemes ml<sup>-1</sup>. Each dilution series was injected intradermally in two rabbits, ten sites per rabbit. Similarly, each dilution was inoculated intratesticularly into two rabbits, four dilutions in a total of eight rabbits. We scored and measured the size of lesions at the injection sites in rabbits inoculated intradermally. We monitored intratesticularly infected rabbits for orchitis. Sera from all animals were tested for seroconversion. We also compared the analytical sensitivity of animal bioassays to that of treponemal PCR.<b>Results.</b> The infectivity titre of <i>T. pallidum</i> was the same whether measured by intradermal or intratesticular inoculations, but the former used 75% fewer animals. Bacterial concentration at 50% endpoint was lower, 4 treponemes ml<sup>-1</sup>, with intratesticular route compared to 25 treponemes ml<sup>-1</sup> using intradermal injections. Nested PCR demonstrated an analytical sensitivity of 40 treponemes ml<sup>-1</sup>, comparable to that obtained with animal bioassays. We also showed a correlation between lesion size and treponemal counts that, under standardized conditions, might be exploited to estimate the number of treponemes in a sample.<b>Conclusions.</b> Our studies showed that all methods tested detected <i>T. pallidum</i> with similar sensitivities. However, the intradermal route might be better suited to investigate clinical specimens as it offered desirable features such as treponemal quantification, minimal number of animals required and detection of live infectious bacteria, all in a single test.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Convergent methodologies in prosthetic joint infection research: integrating transdisciplinary approaches to understand and prevent biofilm-driven failure of orthopaedic prostheses. 假体关节感染研究的趋同方法:整合跨学科方法来理解和预防生物膜驱动的矫形假体失败。
IF 2
Journal of medical microbiology Pub Date : 2026-09-01 DOI: 10.1099/jmm.0.002206
Heather Pinder, Justine K Rudkin, Nathaniel P A Quail, Daniel M Wall, Peter Young, Liam M Rooney
{"title":"Convergent methodologies in prosthetic joint infection research: integrating transdisciplinary approaches to understand and prevent biofilm-driven failure of orthopaedic prostheses.","authors":"Heather Pinder, Justine K Rudkin, Nathaniel P A Quail, Daniel M Wall, Peter Young, Liam M Rooney","doi":"10.1099/jmm.0.002206","DOIUrl":"https://doi.org/10.1099/jmm.0.002206","url":null,"abstract":"<p><p>Prosthetic joint infections (PJIs) remain among the most devastating complications of arthroplasty, imposing substantial clinical, economic and patient burdens. Although culture-based diagnostics underpin current clinical practice, PJIs are biofilm-driven infections shaped by taxonomic diversity, spatial organization, host responses and surface interactions, meaning conventional approaches provide only a partial and often decontextualized view of the infection process. We examine how convergent methodologies can transform PJI research by integrating approaches that have traditionally been studied in isolation, including sequencing, transcriptomics, metabolomics, advanced imaging and culture-based characterization. We discuss how whole-genome sequencing, shotgun metagenomics, transcriptomic and metabolomic approaches resolve pathogen identity, functional activity and adaptive persistence and how cross-scale imaging and spatial biology techniques reveal where microbes colonize, interact and survive across implant surfaces. We highlight emerging opportunities to unify these datasets into coherent frameworks that capture both the molecular and physical dimensions of PJIs. Integrating these complementary approaches will enable a multi-layered understanding of PJIs that link composition, function and spatial organization. Ultimately, this provides a foundation for predictive diagnostics, precision antimicrobial strategies and improved implant design and supports a shift towards more effective, mechanism-informed management of implant-associated infection.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Open question: Can Chlamydia pneumoniae cause persistent infections, and how are these associated with chronic diseases? 开放性问题:肺炎衣原体能否引起持续性感染?这些感染与慢性疾病有何关联?
IF 2
Journal of medical microbiology Pub Date : 2026-09-01 DOI: 10.1099/jmm.0.002200
David L Hahn
{"title":"Open question: Can <i>Chlamydia pneumoniae</i> cause persistent infections, and how are these associated with chronic diseases?","authors":"David L Hahn","doi":"10.1099/jmm.0.002200","DOIUrl":"https://doi.org/10.1099/jmm.0.002200","url":null,"abstract":"","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tetracyclines, a timely resurgence or doomed to fail again? 四环素,及时复苏还是注定再次失败?
IF 2
Journal of medical microbiology Pub Date : 2026-09-01 DOI: 10.1099/jmm.0.002197
Samuel Fenn, Dimitra Panagiotopoulou, Kim R Hardie
{"title":"Tetracyclines, a timely resurgence or doomed to fail again?","authors":"Samuel Fenn, Dimitra Panagiotopoulou, Kim R Hardie","doi":"10.1099/jmm.0.002197","DOIUrl":"https://doi.org/10.1099/jmm.0.002197","url":null,"abstract":"<p><p>Tetracyclines are bacteriostatic antimicrobials used in the treatment of both bacterial and protozoan pathogens. They abolish protein synthesis by binding to the 16S rRNA, blocking aminoacyl-tRNA access and preventing polypeptide elongation. Tetracyclines are polyketide antimicrobials, with members of this drug family (doxycycline, minocycline and tigecycline) on the World Health Organization (WHO) list of essential medicines. Bacterial resistance to this antimicrobial family is widespread and arises via multiple mechanisms. The most common of these resistance mechanisms are tetracycline efflux, ribosomal protection proteins and the newly emerging tetracycline destructases (TDases). The rise of resistance has limited the clinical use of first- and second-generation tetracyclines; however, third-generation tetracyclines are now reserved as antimicrobials of last resort for complicated bacterial infections. However, genetically mobile TDases have now been identified in opportunistic pathogens, with this mechanism of resistance capable of inactivating third-generation tetracyclines. This presents the question, are third-generation tetracyclines doomed to fail in the same manner as first-generation tetracyclines?</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbiota and inflammatory factor profiles in different stages of bacterial vaginosis formation and recurrence. 细菌性阴道病形成和复发的不同阶段的微生物群和炎症因子谱。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002183
Qing Zhu, Yutong Li, Hu Luo
{"title":"Microbiota and inflammatory factor profiles in different stages of bacterial vaginosis formation and recurrence.","authors":"Qing Zhu, Yutong Li, Hu Luo","doi":"10.1099/jmm.0.002183","DOIUrl":"10.1099/jmm.0.002183","url":null,"abstract":"<p><p><b>Introduction.</b> Bacterial vaginosis (BV) is a common gynaecological disorder characterized by an imbalance in the vaginal microbiota, leading to increased risk of infection and recurrence.<b>Hypothesis/Gap statement.</b> Although the role of microbiota dysbiosis in BV is established, the dynamic changes in microbial communities and inflammatory factors during BV formation and recurrence, as well as reliable biomarkers for predicting recurrence, remain inadequately explored.<b>Aim.</b> This study aimed to systematically analyse the changes in vaginal microbiota and inflammatory factors during different stages of BV formation and recurrence, and to identify potential biomarkers for predicting BV recurrence.<b>Methodology.</b> Vaginal swab samples were collected from 135 women, including 55 BV patients, 50 intermediate BV (IBV) patients and 30 healthy controls. Twenty-six recurrent BV (Re-BV) samples were obtained within 1 year after treatment. 16S rRNA gene sequencing was performed to profile the vaginal microbiota, and ELISA was used to measure IL-6, IL-10 and IL-1β levels. Statistical analyses included diversity metrics, correlation analysis and predictive modelling using LASSO regression and receiver operating characteristic curves.<b>Results.</b> Microbial richness was significantly higher in BV, Re-BV and IBV groups compared to controls. <i>Lactobacillus</i> abundance decreased progressively from IBV to BV, while <i>Gardnerella</i>, <i>Prevotella</i>, <i>Sneathia</i>, <i>Fannyhessea</i> and <i>Dialister</i> increased. These genera were positively correlated with vaginal pH, human papillomavirus (HPV) status and enzymatic activity. IL-6, IL-10 and IL-1β levels were elevated in BV, IBV and Re-BV groups. IL-10 and IL-1β were further increased in recurrent cases. A combined predictive model integrating microbial and cytokine markers achieved an area under the curve of 0.928 for BV recurrence.<b>Conclusion.</b> Distinct shifts in vaginal microbiota composition and inflammatory factor levels occur during BV formation and recurrence. The integration of microbial and cytokine profiles offers a robust approach for predicting BV recurrence, with important implications for clinical management and prevention strategies.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of resistance to last-line therapeutic molecules and genetic diversity of Klebsiella spp. strains involved in urinary tract infections in women: the case of Hôpital d'Instruction des Armées Omar Bongo Ondimba. 与妇女尿路感染有关的克雷伯氏菌菌株对最后一线治疗分子的耐药性和遗传多样性的特征:Hôpital d'Instruction des armsames Omar Bongo Ondimba病例。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002190
Evrard Mayombo Ngoussou, Annicet Clotaire Dikoumba, Mundunge Mambu, Rolande Mabika Mabika, Ornella Zong Minko, Franck Mounioko, Léonce Fauster Ondjiangui, Rachel Moyen, Jean Fabrice Yala
{"title":"Characterization of resistance to last-line therapeutic molecules and genetic diversity of <i>Klebsiella</i> spp. strains involved in urinary tract infections in women: the case of Hôpital d'Instruction des Armées Omar Bongo Ondimba.","authors":"Evrard Mayombo Ngoussou, Annicet Clotaire Dikoumba, Mundunge Mambu, Rolande Mabika Mabika, Ornella Zong Minko, Franck Mounioko, Léonce Fauster Ondjiangui, Rachel Moyen, Jean Fabrice Yala","doi":"10.1099/jmm.0.002190","DOIUrl":"10.1099/jmm.0.002190","url":null,"abstract":"<p><p><b>Introduction.</b> <i>Klebsiella</i> spp. are the second most common uropathogens after <i>Escherichia coli</i> and are globally recognized for their high morbidity, driven by their significant ability to develop multi-drug resistance against a wide range of antimicrobials.<b>Hypothesis/Gap Statement.</b> In Central Africa, and particularly in Gabon, there is a significant lack of data regarding the prevalence and genetic diversity of uropathogenic <i>Klebsiella</i> spp. resistant to last-line antibiotics involved in urinary tract infections (UTIs) in women.<b>Aim.</b> This study aims to characterize the resistance of <i>Klebsiella</i> spp. involved in UTIs in women to last-line therapeutic molecules and to explore their genetic diversity through enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) profiling.<b>Methodology.</b> The germs were isolated on Urilines biphasic slides. Identification and susceptibility profiles were performed using the API 20E, ATB Ur and VITEK<sup>®</sup> 2 COMPACT. Molecular research of carbapenemase genes (<i>bla</i> <sub>KPC</sub>, <i>bla</i> <sub>IMP</sub> and <i>bla</i> <sub>VIM</sub>) and resistance to fosfomycin (<i>fos</i>A, <i>fos</i>B, <i>fos</i>C, <i>glpT</i> and <i>uhpT</i>) was made by conventional PCR, and genetic diversity was screened using ERIC-PCR.<b>Results.</b> Of 343 patients, 60.64% (208 out of 343) were women, with a prevalence of UTIs of 43.75% (91 out of 208). The involvement of <i>Klebsiella</i> spp. uropathogens was 29.03% (27 out of 93) against 53.76% (50 out of 93) of other enterobacteria. <i>Klebsiella</i> spp. strains showed high levels of resistance to third-generation cephalosporins (55.56%), fourth-generation cephalosporins and fosfomycin (40.74%), average levels of resistance to third-generation fluoroquinolones (25.92%) and low levels of resistance to carbapenems (7.41%). A total of 81.82% (18 out of 22) of <i>Klebsiella</i> spp. strains possess antibiotic resistance genes, <i>bla</i> <sub>KPC</sub> (40.0%) and <i>fos</i>A (36.0%), respectively. The study of genetic diversity by interpretation of ERIC-PCR profiles shows 19 distinct banding patterns and 2 repeated profiles, all divided into 9 clusters.<b>Conclusion.</b> Uropathogenic <i>Klebsiella</i> spp. isolated from women have high rates of resistance to last-line antibiotics, with the exception of imipenem. They exhibit diverse ERIC-PCR profiles and possess <i>bla</i> <sub>KPC</sub> and <i>fos</i>A. These findings provide important preliminary surveillance data for the region.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ex vivo inhibition of enamel phosphate uptake in Rothia dentocariosa. 牙齿罗汉花牙釉质磷酸盐摄取的体外抑制。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002192
Dhiraj Kumar, Robert S Jones, Beverly E Flood, Jake V Bailey
{"title":"<i>Ex vivo</i> inhibition of enamel phosphate uptake in <i>Rothia dentocariosa</i>.","authors":"Dhiraj Kumar, Robert S Jones, Beverly E Flood, Jake V Bailey","doi":"10.1099/jmm.0.002192","DOIUrl":"10.1099/jmm.0.002192","url":null,"abstract":"<p><p><b>Introduction.</b> Oral bacteria, such as <i>Rothia dentocariosa</i> (<i>Rd</i>), can modulate external aqueous phase orthophosphate (P<sub>i</sub>) concentrations via P<sub>i</sub> internalization and accumulate high amounts of P<sub>i</sub> in the form of polyphosphate (polyP).<b>Hypothesis/Gap Statement.</b> This study investigates whether the carbohydrate metabolism of <i>Rd</i> that generates acid and solubilizes P<sub>i</sub>, derived from phosphorus-32 (<sup>32</sup>P)-labelled tooth enamel, can be internalized and incorporated into intracellular polyP. The study investigated the hypothesis that the internalization of tooth-derived P<sub>i</sub> and polyP synthesis could be attenuated.<b>Aim.</b> A radionuclide <sup>32</sup>P-labelled remineralized model examined the influence of gallein, an inhibitor of polyP kinases, on the ingestion of tooth-derived P<sub>i</sub> and on the bacterium's cultivability.<b>Methodology.</b> Radionuclide <sup>32</sup>P-labelled remineralized bovine enamel (<i>n</i>=6) was exposed to <i>Rd</i> (ATCC 17931) incubated in brain heart infusion (BHI) broth containing glucose. Attenuated total reflectance Fourier transform infrared (FTIR) spectroscopy and cross-polarization optical coherence tomography assessed the surface and subsurface characteristics of the remineralized and demineralized enamel surface. Liquid scintillation traced the <sup>32</sup>P release from the tooth to the intracellular polyP in gallein<sup>pos/neg</sup> samples. Cell-media, supernatant, cell resuspension, and extracted polyP, from <i>Rd</i> exposed to the radioisotope-labelled remineralized enamel, were analysed for <sup>32</sup>P activity at 10 and 22 h time points.<b>Results.</b> FTIR determined that <sup>32</sup>P was incorporated in dental enamel lesions and was released after exposure to an acidic buffer (pH=4.5) or <i>Rd</i>. After 24 h of exposure, gallein<sup>pos</sup> reduced <i>Rd</i>'s planktonic growth and increased pH by 7.45% and 7.19%, respectively, compared to gallein<sup>neg</sup>. Gallein inhibited the cultivability of planktonic <i>Rd</i> on BHI agar plates with a 13- to 60-fold reduction of c.f.u. ml<sup>-1</sup> (25 µM-13.03×, 50 µM-19.58× and 100 µM-60.57×) compared to gallein<sup>neg</sup> samples. Isotope labelling demonstrated that <i>Rd</i> used P<sub>i</sub> derived directly from the tooth for the benefit of the bacterium's fitness through the formation of polyP.<b>Conclusion.</b> <i>Rd</i> used the P<sub>i</sub> derived directly from the tooth for the benefit of the bacterium's fitness. Gallein attenuated polyP accumulation, reduced bacterial cultivability and may be a potential therapy option in the prevention and treatment of primary and secondary caries.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biofilm sensitization to break Staphylococcus aureus tolerance to cold atmospheric plasma therapy. 生物膜致敏以打破金黄色葡萄球菌对低温大气等离子体治疗的耐受性。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002193
Abdullah Baz, Jontana Allkja, Muhanna Alshehri, Yao He, Zainab Bilal, Eve Hughes, Olivia Sealy, Craig Williams, Karen Faulds, Gordon Ramage, Jason L Brown
{"title":"Biofilm sensitization to break <i>Staphylococcus aureus</i> tolerance to cold atmospheric plasma therapy.","authors":"Abdullah Baz, Jontana Allkja, Muhanna Alshehri, Yao He, Zainab Bilal, Eve Hughes, Olivia Sealy, Craig Williams, Karen Faulds, Gordon Ramage, Jason L Brown","doi":"10.1099/jmm.0.002193","DOIUrl":"10.1099/jmm.0.002193","url":null,"abstract":"<p><p><b>Introduction.</b> Biofilm-associated infections present a major therapeutic challenge due to their intrinsic tolerance to conventional antimicrobials. Cold atmospheric plasma (CAP) has shown promise as a non-antibiotic antimicrobial modality; however, some bacteria including <i>Staphylococcus aureus</i> can exhibit tolerance to plasma exposure.<b>Gap Statement.</b> Strategies that sensitize CAP-tolerant biofilms to plasma treatment may improve CAP efficacy, but suitable adjunctive compounds and mechanisms remain poorly defined.<b>Aim.</b> This study aimed to determine whether repurposed bioactive compounds could enhance CAP activity against <i>S. aureus</i> biofilms.<b>Methodology.</b> Selected compounds from the Tocriscreen™ bioactive compound library were initially screened, followed by treatment of <i>S. aureus</i> biofilms with KHS101 ±CAP therapy. Biofilm viability was quantified using live/dead qPCR. To probe mechanisms of sensitization, biofilms were exposed to H<sub>2</sub>O<sub>2</sub> at concentrations equivalent to those generated by CAP, either alone, or in combination with KHS101 or conventional antibiotics. Various microscopy techniques were used to visualize the cellular impacts of KHS101, while metabolic activity and cell viability of dual therapies were determined using AlamarBlue<sup>®</sup> assay and plate count assays, respectively.<b>Results.</b> Short-term KHS101 treatment alone displayed modest antibiofilm activity at concentrations that inhibited planktonic growth. However, pre-treatment with KHS101 followed by CAP therapy resulted in significant reductions in viable populations in <i>S. aureus</i>-containing biofilms. Microscopy revealed structural perturbations consistent with cellular stress following KHS101 exposure, but also showed intact cellular ultrastructure. Mechanistic probing demonstrated that equivalent concentrations of H<sub>2</sub>O<sub>2</sub> with KHS101 were insufficient to reproduce the enhanced efficacy observed with CAP. In contrast, H<sub>2</sub>O<sub>2</sub> enhanced flucloxacillin activity in a strain-dependent manner, sensitizing <i>S. aureus</i> biofilms to otherwise sub-lethal concentrations of antibiotic.<b>Conclusion.</b> These findings demonstrate that tolerance of <i>S. aureus</i> biofilms to CAP can be overcome through dual-therapy strategies. Treatment with the repurposed compound KHS101 was associated with enhancement of CAP efficacy via an unknown mechanism. However, the inability of H<sub>2</sub>O<sub>2</sub> to reproduce this effect highlights the importance of additional plasma-derived reactive species in mediating this dual-action killing. Together, these findings position biofilm sensitization as a central concept emerging from this study, whereby a non-lethal adjunct can lower the threshold for CAP-mediated killing without acting primarily as a direct antimicrobial.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brucella suis vaccine strain 2 promotes intracellular proliferation by inducing M2 macrophage polarization and autophagy through PI3K/Akt/mTOR signalling. 猪布鲁氏菌疫苗2株通过PI3K/Akt/mTOR信号传导诱导M2巨噬细胞极化和自噬,促进细胞内增殖。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002182
Haining Li, Juan Yang, Ting Xu, Zhang Ji, Zhenhai Wang
{"title":"<i>Brucella suis</i> vaccine strain 2 promotes intracellular proliferation by inducing M2 macrophage polarization and autophagy through PI3K/Akt/mTOR signalling.","authors":"Haining Li, Juan Yang, Ting Xu, Zhang Ji, Zhenhai Wang","doi":"10.1099/jmm.0.002182","DOIUrl":"10.1099/jmm.0.002182","url":null,"abstract":"<p><p><b>Introduction.</b> The persistent intracellular survival of <i>Brucella</i> is a key factor contributing to immune evasion and chronic infection as evidenced by clinical recurrence. This ability of establishing long-term intracellular residency is a major driver of brucellosis relapse. Pathogens such as <i>Brucella</i> often manipulate host cell polarization and exploit autophagy to sustain their intracellular survival.<b>Hypothesis/Gap Statement.</b> Real-world understanding of how macrophage polarization and autophagy jointly influence <i>Brucella</i> intracellular replication remains limited, and the specific signalling pathways mediating this interaction have not been fully characterized.<b>Aim.</b> This study aimed to investigate the interplay between macrophage polarization, autophagy and intracellular proliferation of <i>Brucella suis</i> strain 2 and to characterize the involvement of the PI3K/AKT/mTOR signalling pathway in this process.<b>Methodology.</b> We examined infection-induced alterations in BV2 cell polarization and autophagic activity following <i>Brucella</i> S2 infection. Autophagy-related protein expression (LC3B-I, LC3B-II, ULK1 and p62) was assessed by Western blot, and autophagosome-to-autolysosome conversion was visualized by laser confocal microscopy. Macrophage polarization markers (iNOS and Arg1) and cytokine secretion (TNF-<i>α</i> and IL-10) were measured by ELISA. Intracellular bacterial replication was quantified by c.f.u. assays, and pharmacological inhibitors were used to modulate PI3K/Akt/mTOR signalling and autophagic activity.<b>Results.</b> Following <i>Brucella</i> S2 infection in BV2 cells, we observed elevated expression of iNOS, Arg1, p-Akt, mTOR and autophagy-related proteins (LC3B-I, LC3B-II and ULK1), accompanied by decreased p62 levels. Laser confocal microscopy revealed efficient autophagosome-to-autolysosome conversion. Time-dependent increases in TNF-<i>α</i> and IL-10 secretion indicated macrophage plasticity and the establishment of a mixed M1/M2 phenotype. c.f.u. assays demonstrated that PI3K/Akt/mTOR inhibition and autophagy induction promoted <i>Brucella</i> S2 intracellular proliferation. Notably, pharmacological inhibition of the PI3K/Akt/mTOR pathway reversed this effect by promoting M1 polarization while suppressing autophagic activity.<b>Conclusion.</b> Collectively, our findings demonstrate that <i>Brucella</i> S2 infection induces both M1/M2 mixed polarization and autophagic activation in BV2 cells. Importantly, we identified that the M2-polarized state and autophagy induction synergistically promote intracellular bacterial replication, a process mediated through the PI3K/Akt/mTOR signalling pathway. These results suggest that targeted modulation of PI3K/Akt/mTOR signalling could represent a promising therapeutic approach to control <i>Brucella</i> S2 intracellular proliferation.</p>","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: In vitro synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of Brucella melitensis. 更正:短阳离子肽和临床使用的抗生素对耐药布鲁氏菌的体外协同作用。
IF 2
Journal of medical microbiology Pub Date : 2026-08-01 DOI: 10.1099/jmm.0.002201
Zohreh Mohammadi Azad, Hoda Moravej, Mahdi Fasihi-Ramandi, Faramarz Masjedian, Raziyeh Nazari, Reza Mirnejad, Mehrdad Moosazadeh Moghaddam
{"title":"Erratum: <i>In vitro</i> synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of <i>Brucella melitensis</i>.","authors":"Zohreh Mohammadi Azad, Hoda Moravej, Mahdi Fasihi-Ramandi, Faramarz Masjedian, Raziyeh Nazari, Reza Mirnejad, Mehrdad Moosazadeh Moghaddam","doi":"10.1099/jmm.0.002201","DOIUrl":"https://doi.org/10.1099/jmm.0.002201","url":null,"abstract":"","PeriodicalId":94093,"journal":{"name":"Journal of medical microbiology","volume":"75 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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