{"title":"Mycoplasma pneumoniae drives macrophage lipid uptake via GlpD-mediated oxidation, facilitating foam cell formation.","authors":"Takeshi Yamamoto, Miki Okuno, Koichi Kuwano, Yoshitoshi Ogura","doi":"10.1016/j.ijmm.2025.151646","DOIUrl":"https://doi.org/10.1016/j.ijmm.2025.151646","url":null,"abstract":"<p><p>Cardiovascular diseases, primarily caused by atherosclerosis, are a major public health concern worldwide. Atherosclerosis is characterized by chronic inflammation and lipid accumulation in the arterial wall, leading to plaque formation. In this process, macrophages play a crucial role by ingesting lipids and transforming into foam cells, which contribute to plaque instability and cardiovascular events. Recent studies have suggested that various pathogens are involved in the development of atherosclerosis, with Mycoplasma pneumoniae considered one of the potential candidates. Therefore, this study investigated whether this bacterium induces lipid accumulation in macrophages, which play a crucial role in the development of atherosclerosis, using the Raw264.7 model. Our findings revealed that M. pneumoniae infection promotes lipid droplet formation in macrophages. Glycerol 3-phosphate oxidase, GlpD, in the bacterium is involved in this process by producing reactive oxygen species, which in turn causes the oxidation of low-density lipoprotein. Furthermore, the significant increase in the expression of oxidized lipid receptors involved in the uptake of this oxidized lipid indicates that the bacteria promote lipid uptake in infected macrophages. These results suggest that M. pneumoniae has a direct pro-atherogenic effect, promoting the formation of atherosclerotic lesions through foam cell formation. Understanding the mechanisms by which M. pneumoniae influences atherosclerosis provides valuable insights for devising new therapeutic strategies for the prevention and management of cardiovascular diseases.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151646"},"PeriodicalIF":4.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042877","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}
Nahed Al Laham, Ahmed Al Afifi, Alexander Mellmann, Frieder Schaumburg
{"title":"Characterization of carbapenem-resistant Klebsiella pneumoniae from blood cultures in Gaza Strip hospitals, Palestine.","authors":"Nahed Al Laham, Ahmed Al Afifi, Alexander Mellmann, Frieder Schaumburg","doi":"10.1016/j.ijmm.2025.151645","DOIUrl":"https://doi.org/10.1016/j.ijmm.2025.151645","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult to treat organism owing to limited therapeutic options. So far, little is known about the molecular characteristics of CRKP in Palestine.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the antimicrobial resistance patterns, multilocus sequence types (ST) and resistance genes among clinical K. pneumoniae isolates from hospitalized patients in Gaza Strip, Palestine.</p><p><strong>Methods: </strong>K. pneumoniae from blood cultures (n = 55) were collected at two hospitals in Gaza Strip (2023) and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing was done using VITEK-2 automated systems. Carbapenemases were phenotypically detected. Whole genome sequencing (WGS) of all CRKP isolates was performed to assess determinants for carbapenem resistance and genotypes.</p><p><strong>Results: </strong>Of all K. pneumoniae isolates, 40 % (n = 22/55) were CRKP. Among CRKP, cefiderocol showed the least resistance (46 %, n = 10/22) while ceftazidime/avibactam showed a synergistic effect with aztreonam (36 %, n = 8/22). The majority (86 %, n = 19/22) of CRKP carried metallo-β-lactamases, and only 9 % (n = 2/22) encoded OXA-48 carbapenemase. WGS of CRKP revealed that the predominant genotype is multilocus sequence type ST147 harboring bla<sub>NDM-5</sub> and bla<sub>CTX-M-15</sub>.</p><p><strong>Conclusion: </strong>The proportion of CRKP among all K. pneumoniae from bloodstream infection in Gaza Strip is high (40 %) and mainly associated with the bla<sub>NDM-5</sub>-positive high-risk clone ST147.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151645"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958167","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}
Roman Chlibek, Jan Smetana, Kateřina Kybicová, Martina Malikova, Frederick J Angulo, Alexandra Loew-Baselli, Ye Tan, Aleš Ondřejíček, Gordon Brestrich, Andreas Pilz, Jennifer C Moïsi, James H Stark
{"title":"Prevalence of Borrelia burgdorferi sensu lato infection in the Czech Republic.","authors":"Roman Chlibek, Jan Smetana, Kateřina Kybicová, Martina Malikova, Frederick J Angulo, Alexandra Loew-Baselli, Ye Tan, Aleš Ondřejíček, Gordon Brestrich, Andreas Pilz, Jennifer C Moïsi, James H Stark","doi":"10.1016/j.ijmm.2024.151644","DOIUrl":"https://doi.org/10.1016/j.ijmm.2024.151644","url":null,"abstract":"<p><strong>Introduction: </strong>Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections.</p><p><strong>Methods: </strong>Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 -2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory. The incidence of symptomatic Bbsl infections was estimated from the seroprevalence results and the symptomatic proportion and duration of persistence of anti-Bbsl IgG antibodies in Bbsl-infected individuals. Surveillance under-detection of symptomatic Bbsl infections was estimated by comparing surveillance-reported and seroprevalence-based incidence.</p><p><strong>Results: </strong>Samples from 1996 adults were tested; the median age (range) was 45 (18 -87) years; 1037 (52.0 %) were female. The prevalence (with 95 % confidence interval) of anti-Bbsl IgG, and IgM and/or IgG (IgM/IgG) antibodies was 6.3 % (5.3 -7.5 %), and 9.5 % (8.3 -10.9 %), respectively. The IgM/IgG prevalence was 7.8 % (6.5 -9.2 %) in Bohemia and 15.3 % (12.2 -19.0 %) in Moravia. There were an estimated 30,563 (26,550 -34,962) symptomatic incident Bbsl infections in adults in the Czech Republic in 2012, for an incidence of 352.2 (306.0 -402.9) symptomatic Bbsl infections per 100,000 adults per year. There were an estimated 11 (10 -13) symptomatic Bbsl infections for each surveillance-reported LB case in the Czech Republic in 2012.</p><p><strong>Conclusions: </strong>There is high incidence of symptomatic Bbsl infections in the Czech Republic, particularly in Moravia. Interventions are needed to address the substantial burden of LB in the Czech Republic.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151644"},"PeriodicalIF":4.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958168","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}
Lisa Maria Kleine, Emmanuel Marx Kanu, Tobias Grebe, Desmond Mohamed Sesay, Henning Loismann, Maxwell Sesay, Tom Theiler, Viktoria Rudolf, Alexander Mellmann, Laura C Kalkman, Martin P Grobusch, Frieder Schaumburg
{"title":"Nasopharyngeal carriage of Staphylococcus aureus in a rural population, Sierra Leone.","authors":"Lisa Maria Kleine, Emmanuel Marx Kanu, Tobias Grebe, Desmond Mohamed Sesay, Henning Loismann, Maxwell Sesay, Tom Theiler, Viktoria Rudolf, Alexander Mellmann, Laura C Kalkman, Martin P Grobusch, Frieder Schaumburg","doi":"10.1016/j.ijmm.2024.151643","DOIUrl":"https://doi.org/10.1016/j.ijmm.2024.151643","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal colonization with Staphylococcus aureus is a risk factor for subsequent infection. Isolates from colonization can therefore provide important information on virulence factors and antimicrobial resistance when data from clinical isolates are lacking. The aim of this study was to assess colonization rates, resistance patterns and selected virulence factors of S. aureus from rural Sierra Leone.</p><p><strong>Methods: </strong>Residents of randomly selected houses in Masanga, Sierra Leone were included in a cross-sectional study (8-11/2023). Participants were tested for nasopharyngeal S. aureus colonization using selective culture media. Risk factors for colonization were documented in a standardized questionnaire. Isolates were genotyped and tested for antimicrobial susceptibility and selected virulence factors (e.g. Panton-Valentine leukocidin, capsular types).</p><p><strong>Results: </strong>Of 300 participants (62.7 % females, median age: 16 years), 168 (56 %) were colonized with S. aureus-related complex; six participants carried two different S. aureus genotypes, resulting in a total number of 174 isolates. Resistance to penicillin was predominant (97.1 %, 169/174), followed by tetracycline (66.1 %, 115/174), co-trimoxazole (56.9 %, 99/174) and oxacillin (24.1 %, 42/174, all mecA-positive, mostly associated with ST8/PVL-negative). PVL gene was detected in 21.3 % of isolates (37/174) mainly associated with ST15 and ST152. Except for past use of antimicrobials (p = 0.019), no specific risk factors such as comorbidities including hemoglobin variants were associated with S. aureus nasopharyngeal colonization.</p><p><strong>Conclusion: </strong>The prevalence of methicillin-resistant and PVL-positive methicillin-susceptible S. aureus (MRSA/MSSA) is high in a rural community of asymptomatic carriers in Sierra Leone. Measures to contain the spread of MRSA, also in the community, are needed.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151643"},"PeriodicalIF":4.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933443","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}
{"title":"E. coli Nissle 1917 improves gut microbiota composition and serum metabolites to counteract atherosclerosis via the homocitrulline/Caspase 1/NLRP3/GSDMD axis.","authors":"Huan Liu, Xiaofeng Ma, Xuefeng Yang, Sujun Xiao, Shao Ouyang, Zhihao Hu, Zhixiang Zhou, Zhisheng Jiang","doi":"10.1016/j.ijmm.2024.151642","DOIUrl":"https://doi.org/10.1016/j.ijmm.2024.151642","url":null,"abstract":"<p><strong>Background: </strong>The probiotic E. coli Nissle 1917 (EcN) alleviates the progression of various diseases, including colitis and tumors. However, EcN has not been studied in atherosclerosis. The study investigated the effects of EcN on atherosclerosis model mice and the potential mechanisms.</p><p><strong>Methods: </strong>Mice in the high-fat diet (HFD) model were given EcN (1 × 10<sup>9</sup> CFU/g) or homocitrulline (150 mg/L) by oral administration for 12 weeks. The EcN + antibiotic group was set up to investigate the effects of EcN combined with antibiotics on gut microbiota. The control group was utilized as the negative control. Atherosclerosis status, pyroptosis, gut microbiota, and serum metabolites of mice were examined.</p><p><strong>Results: </strong>EcN treatment alleviated HFD-caused atherosclerotic plaque and lipid droplet production. EcN treatment reversed HFD-induced increases in total cholesterol, triglycerides, and low-density lipoprotein levels and decreases in high-density lipoprotein levels. EcN inhibited the HFD-caused rise in the expression of pyroptosis-related indicators (cleaved Caspase 1, GSDMD-N, NLRP3, IL-18, and IL-1β). The antibiotics partially reversed the effects of EcN on the model mice, suggesting that EcN regulated pyroptosis in the model mice through gut microbiota. Probiotic bacteria, such as Lactobacillus and Muribaculum, were mainly enriched in the EcN and EcN + antibiotic groups, while Helicobacter, Alistipes, and Rikenella were depleted, suggesting that EcN and EcN + antibiotics could alleviate disorders of gut microbiota in the model mice. EcN reversed the trend of HFD-induced decrease of some metabolites, such as 2-methyl-5-nitroimidazole-1-ethanol, methionine sulfoxide, and shikimate 3-phosphate, and inhibited the increase of some metabolites, such as kynurenine, oxoadipate, and homocitrulline. In addition, homocitrulline showed the opposite effects of EcN in the model mice. Homocitrulline could bind to pyroptosis-related proteins to aggravate ox-LDL-induced endothelial cell pyroptosis.</p><p><strong>Conclusion: </strong>EcN could alleviate atherosclerosis development by ameliorating HFD-induced disorders of gut microbiota and serum metabolites (such as homocitrulline) to alleviate pyroptosis, which may be associated with homocitrulline/Caspase 1/NLRP3/GSDMD axis. Our study lays the foundation for the development of promising drugs for atherosclerosis in the future.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151642"},"PeriodicalIF":4.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916117","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}
Jasmin Adam, Lisa-Marie Graf, Stefanie Westermann, David Voehringer, Sven Krappmann
{"title":"Signaling events driving Aspergillus fumigatus-induced eosinophil activation.","authors":"Jasmin Adam, Lisa-Marie Graf, Stefanie Westermann, David Voehringer, Sven Krappmann","doi":"10.1016/j.ijmm.2024.151641","DOIUrl":"https://doi.org/10.1016/j.ijmm.2024.151641","url":null,"abstract":"<p><p>Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold Aspergillus fumigatus. This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by A. fumigatus, we used an in vitro coculture system of murine bone marrow-derived eosinophils confronted with conidia. Using small-molecule inhibitors, we identified signaling modules of eosinophils in the course of A. fumigatus confrontation. Eosinophils reduced fungal metabolic activity, but inhibition of relevant signaling modules did not affect this phenomenon upon eosinophil confrontation. A. fumigatus-induced secretion of Th2 cytokines and chemokines by eosinophils engaged proto-oncogene tyrosine-protein kinase Src, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase as well as calcium cations and to some extent serine/threonine-protein kinase Akt and protein arginine deiminase 4. Src and PI3K kinases were also involved in A. fumigatus-mediated ROS production and regulation of eosinophils surface receptors. Especially Src and PI3K inhibitors prevented A. fumigatus-induced eosinophil activation. Taken together, identification of signaling cascades of eosinophils during their interaction with A. fumigatus provides relevant insights into the host-pathogen interaction in the context of ABPA to yield therapeutic perspectives.</p>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"151641"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886397","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}
{"title":"Aspergillus fumigatus sensu stricto genetic diversity from cystic fibrosis patients","authors":"Aryse Martins Melo , Vanice Rodrigues Poester , Mariana Rodrigues Trápaga , Fernando Azevedo Faria , Valério Aquino , Cecília Bittencourt Severo , David A. Stevens , Cristina Veríssimo , Raquel Sabino , Melissa Orzechowski Xavier","doi":"10.1016/j.ijmm.2024.151639","DOIUrl":"10.1016/j.ijmm.2024.151639","url":null,"abstract":"<div><div>We aimed to access the genetic diversity of <em>Apergillus fumigatus</em> strains obtained from cystic fibrosis (CF) patients from southern Brazil. <em>A. fumigatus</em> sensu stricto isolates from respiratory clinical specimens were genotyped by microsatellite markers and azole resistance was evaluated by azole-agar screening. Twenty-seven isolates from twenty-seven patients showed a high genetic diversity, with the differentiation of 25 different genotypes (25 unique and one common to two isolates). All isolates were susceptible to the azoles tested. We believe that prospectively monitoring <em>A. fumigatus</em> genetic diversity is essential to identify interpatient transmission and outbreaks, as is the identification of resistant strains.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"317 ","pages":"Article 151639"},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Huang , Jiaru Zhuang , Lin Wan , Yutong Liu , Yiran Du , Lu Zhou , Renjing Hu , Lanfeng Shen
{"title":"Genomic Analysis and Virulence Assessment of Hypervirulent Klebsiella pneumoniae K16-ST660 in Severe Cervical Necrotizing Fasciitis","authors":"Jun Huang , Jiaru Zhuang , Lin Wan , Yutong Liu , Yiran Du , Lu Zhou , Renjing Hu , Lanfeng Shen","doi":"10.1016/j.ijmm.2024.151635","DOIUrl":"10.1016/j.ijmm.2024.151635","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the source of infection in a patient with recurrent severe neck infections caused by <em>Klebsiella pneumoniae</em> and to analyze the virulence of isolates obtained from different sites of the patient.</div></div><div><h3>Methods</h3><div>We collected preoperative neck abscess puncture fluid, intraoperative neck drainage fluid, sputum, intestinal fecal specimens, and blood samples from a patient who visited Wuxi Second People's Hospital twice between 2017 and 2018. We conducted isolation, identification, drug sensitivity tests, and string tests on the isolates. Capsule serotyping and virulence gene analysis were performed using PCR. The genetic relationship of different isolates was assessed by Multilocus Sequence Typing and virulence was evaluated using the Galleria mellonella infection model. Additionally, whole-genome sequencing was used to analyze the chromosomal and plasmid genes of one isolate.</div></div><div><h3>Results</h3><div><em>Klebsiella pneumoniae</em> was detected in the sputum and fecal specimens from both hospitalizations, as well as the preoperative ultrasound-guided puncture fluid and intraoperative drainage fluid from the first hospitalization, resulting in six isolates. These isolates were all K16 serotype, positive in the string test, and identified as ST660 by Multilocus Sequence Typing, indicating they belonged to the same clone. Virulence gene analysis showed that <em>wcaG, iucB, iroNB, rmpA, rmpA2, Aer, kfuBC, ureA, fimH, mrkD, uge</em>, and <em>peg344</em> were positive, while <em>allS, cf29a</em>, and <em>Wzy_K1</em> were negative. In the Galleria mellonella virulence assay, the lethality of different isolates was dose-dependent. The K16 group showed significantly higher larval mortality compared to other control groups (including K1, K2, K5, K20, and K57 groups). Genome sequencing revealed that plasmid p17388 carried numerous virulence genes and insertion sequences, particularly <em>ISKPN74</em>, and showed high homology with other Klebsiella plasmids.</div></div><div><h3>Conclusion</h3><div>This study is the first to report severe cervical necrotizing fasciitis caused by the K16-ST660 <em>Klebsiella pneumoniae</em> Isolate. The high virulence of these isolates was confirmed by the Galleria mellonella virulence assay and the detection of numerous virulence genes. In-depth analysis of plasmid p17388 suggests that ISKPN74 may enhance stable integration of the plasmid into the bacterial chromosome through recombinases and transposases, thereby reducing the likelihood of plasmid loss and increasing bacterial virulence. Additionally, IS5 family insertion sequences may carry extra promoters or enhancers that, when inserted upstream of mucoviscosity-associated genes such as rmpA, may increase the transcription levels of downstream genes. This ISKPN74-mediated integration or insertion reveals a complex genetic mechanism that may contribute to the severity of infections caused by ST","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"317 ","pages":"Article 151635"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co-transcribed genes SA1833-SA1832 promote persister formation by regulating the transcription of holin-like gene lrgA in methicillin-resistant Staphylococcus aureus strain N315","authors":"Shiwen Xu , Jiade Zhu , Yujie Li , Baolin Sun","doi":"10.1016/j.ijmm.2024.151636","DOIUrl":"10.1016/j.ijmm.2024.151636","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em>, a facultative anaerobic gram-positive bacterial pathogen, has posed major threat to public health worldwide. Upon <em>S. aureus</em> infection, the host immune system is activated for clearance. However, intracellular <em>S. aureus</em>, which remains viable for an extended time, has evolved the ability to escape from immune response and extracellular antibiotics. One of possible strategies is the formation of persisters. Persistence is one of the major causes of <em>S. aureus</em> relapse infection but the underlying mechanisms remain obscure. Here, we identified two co-transcribed genes <em>SA1833-SA1832</em> that are involved in persister formation in <em>S. aureus</em>. Dysfunction of <em>SA1833</em> and/or <em>SA1832</em> significantly reduces persister formation in the presence of ceftizoxime. Additionally, we found that the expression of <em>SA1833</em> and <em>SA1832</em> under the induction of oxidative stress and SOS response is strictly regulated by the LexA-RecA pathway. Interestingly, <em>SA1833-SA1832</em> contributes to persister formation in an <em>lrgA</em>-dependent manner. Moreover, the mouse RAW264.7 macrophage infection model indicated that disrupting <em>SA1833-SA1832</em> inhibits <em>S. aureus</em> from infecting macrophages and impairs its ability to survive in the intracellular environment.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"317 ","pages":"Article 151636"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nurul Amirah Mohamad Farook , Silvia Argimón , Muttaqillah Najihan Abdul Samat , Sharifah Azura Salleh , Sunita Sulaiman , Toh Leong Tan , Petrick Periyasamy , Chee Lan Lau , Nor Azila Muhammad Azami , Raja Mohd Fadhil Raja Abd Rahman , Mia Yang Ang , Hui-min Neoh
{"title":"Desiccation tolerance and reduced antibiotic resistance: Key drivers in ST239-III to ST22-IV MRSA clonal replacement at a Malaysian teaching hospital","authors":"Nurul Amirah Mohamad Farook , Silvia Argimón , Muttaqillah Najihan Abdul Samat , Sharifah Azura Salleh , Sunita Sulaiman , Toh Leong Tan , Petrick Periyasamy , Chee Lan Lau , Nor Azila Muhammad Azami , Raja Mohd Fadhil Raja Abd Rahman , Mia Yang Ang , Hui-min Neoh","doi":"10.1016/j.ijmm.2024.151638","DOIUrl":"10.1016/j.ijmm.2024.151638","url":null,"abstract":"<div><div>Molecular surveillance of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) isolated from Hospital Canselor Tuanku Muhriz (HCTM), a Malaysian teaching hospital revealed clonal replacement events of SCC<em>mec</em> type III-SCC<em>mercury</em> to SCC<em>mec</em> type IV strains before the year 2017; however, the reasons behind this phenomenon are still unclear. This study aimed to identify factors associated with the clonal replacement using genomic sequencing and phenotypic investigations (antibiogram profiling, growth rate and desiccation tolerance determination, survival in vancomycin sub-minimum inhibitory concentration (MIC) determination) of representative HCTM MRSA strains isolated in four-year intervals from 2005 – 2017 (n = 16). HCTM Antimicrobial Stewardship (AMS) and Infection Prevention and Control (IPC) policies were also reviewed. Phylogenetic analyses revealed the presence of 3 major MRSA lineages: ST239-III, ST22-IV and ST6-IV; MRSAs with the same STs shared similar core and accessory genomes. Majority of the ST239-III strains isolated in earlier years of the surveillance (2005, 2009 and 2013) were resistant to many antibiotics and harboured multiple AMR and virulence genes compared to ST22-IV and ST6-IV strains (isolated in 2013 and 2017). Interestingly, ST22-IV and ST6-IV MRSAs grew significantly faster and were more resistant to desiccation than ST239-III (<em>p</em> < 0.05), even though the later clone survived better post-vancomycin exposure. Intriguingly, ST22-IV was outcompeted by ST239-III in broth co-cultures; though it survived better when desiccated together with ST239-III. Higher desiccation tolerance and fewer carriage of AMR genes by ST22-IV, together with reduction of antibiotic selection pressure in HCTM (due to AMS and IPC policies) during 2005 – 2017 may have provided the clone a competitive edge in replacing the previously dominant ST239-III in HCTM. This study highlights the importance of MRSA surveillance for a clearer picture of circulating clones and clonal changes. To our knowledge, this is the first genomic epidemiology study of MRSA in Malaysia, which will serve as baseline genomic data for future surveillance.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"317 ","pages":"Article 151638"},"PeriodicalIF":4.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}