Microbiology and Immunology最新文献

{"title":"Persistent Epstein–Barr Virus Infection of Epithelial Cells Leads to APOBEC3C Expression and Induces Mitochondrial DNA Mutations","authors":"Aung Phyo Wai,&nbsp;Timmy Richardo,&nbsp;Kousho Wakae,&nbsp;Shunpei Okada,&nbsp;Masamichi Muramatsu,&nbsp;Hironori Yoshiyama,&nbsp;Hisashi Iizasa","doi":"10.1111/1348-0421.13196","DOIUrl":"10.1111/1348-0421.13196","url":null,"abstract":"<div>\u0000 \u0000 <p>Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C-to-T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein–Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection. However, because viral resistance factors are not expressed during EBV latent infection, it is unknown how APOBEC3 functions during latent infection. We observed that in gastric epithelial cells persistently infected with EBV, the expression of APOBEC3 family genes increased, C-to-T mutations in the D-loop genome of mitochondrial DNA (mtDNA) increased, and mtDNA copy number decreased. By introducing and expressing individual APOBEC3 family genes, APOBEC3C was particularly expressed in the cytoplasm, increasing C-to-T mutations in mtDNA and decreasing mtDNA copy number. Furthermore, we confirmed that APOBEC3C co-localized with mitochondria in EBV-infected cells. Expression of the EBV latent gene LMP2A increased APOBEC3C expression. Conversely, APOBEC3C expression was reduced in LMP2A-deficient EBV-infected cells compared to wild-type EBV-infected cells. These results indicate that persistent infection of EBV in gastric epithelial cells reduces the number of mitochondria through mtDNA mutations induced by APOBEC3C expression.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 3","pages":"157-167"},"PeriodicalIF":1.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species","authors":"Natsuko Ota,&nbsp;Takashi Nishida,&nbsp;Daron M. Standley,&nbsp;Aalaa Alrahman Sherif,&nbsp;Satoshi Iwano,&nbsp;Dendi Krisna Nugraha,&nbsp;Toshiya Ueno,&nbsp;Yasuhiko Horiguchi","doi":"10.1111/1348-0421.13193","DOIUrl":"10.1111/1348-0421.13193","url":null,"abstract":"<p>The Gram-negative bacteria <i>Bordetella pertussis</i>, <i>B. parapertussis</i>, and <i>B. bronchiseptica</i> cause respiratory diseases in various mammals. They share the BvgAS two-component system, which regulates the phenotypic conversion between the virulent Bvg⁺ and avirulent Bvg^– phases. In the BvgAS system, the sensor kinase BvgS senses environmental cues and transduces a phosphorelay signal to the response regulator BvgA, which leads to the expression of Bvg⁺ phase-specific genes, including virulence factor genes. Bacteria grown at 37°C exhibit the Bvg⁺ phenotype. In contrast, at lower than 26°C or in the presence of modulators, such as MgSO₄ and nicotinic acid, the BvgAS system is inactivated, leading bacteria to the avirulent Bvg^– phase. Therefore, effective modulators are expected to provide a therapeutic measure for <i>Bordetella</i> infection; however, no such modulators are currently available, and the mechanism by which modulators inactivate the BvgAS system is poorly understood. In the present study, we identified lonidamine as a novel modulator after screening an FDA-approved drug library using bacterial reporter systems with the Bvg⁺-specific and Bvg^–-specific promoters. Lonidamine directly bound to the VFT2 domain of BvgS and inactivated the BvgAS system at concentrations as low as 50 nM, which was at least 2000- to 20,000-fold lower than the effective concentrations of known modulators. Lonidamine significantly reduced the adherence of <i>B. pertussis</i> to cultured cells but unexpectedly exacerbated bacterial colonization of the mouse nasal septum. These results provide insights into the structural requirements for BvgAS modulators and the role of Bvg phenotypes in the establishment of infection.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 3","pages":"133-147"},"PeriodicalIF":1.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategy to Identify Virulence-Related Genes of the Pathogenic Fungus Trichosporon asahii Using an Efficient Gene-Targeting System","authors":"Yasuhiko Matsumoto,&nbsp;Sanae Kurakado,&nbsp;Tsuyoshi Yamada,&nbsp;Takashi Sugita","doi":"10.1111/1348-0421.13192","DOIUrl":"10.1111/1348-0421.13192","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Trichosporon asahii</i> is a pathogenic fungus that causes severe deep-seated mycosis in immunocompromised patients with neutropenia. Understanding the molecular mechanisms of <i>T. asahii</i> infection will facilitate the development of new therapeutic and preventive strategies. Two main obstacles have prevented the identification of virulence-related genes in <i>T. asahii</i> using molecular genetic techniques: the lack of experimental animal infection models for easy evaluation of <i>T. asahii</i> virulence and the lack of genetic recombination technology for <i>T. asahii</i>. To address these issues, we developed a silkworm infection model to quantitatively evaluate <i>T. asahii</i> virulence and a genetic recombination method to generate gene-deficient <i>T. asahii</i> mutants, enabling the identification of virulence factors of <i>T. asahii</i>. In this review, we propose a strategy for identifying virulence-related factors in <i>T. asahii</i> using a silkworm infection model and an efficient gene-targeting system.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 2","pages":"77-84"},"PeriodicalIF":1.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewers List","authors":"","doi":"10.1111/1348-0421.13194","DOIUrl":"10.1111/1348-0421.13194","url":null,"abstract":"","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"68 12","pages":"438-439"},"PeriodicalIF":1.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13186","DOIUrl":"https://doi.org/10.1111/1348-0421.13186","url":null,"abstract":"<p><b>Cover photograph</b>: Representation of the E6 + Lumacaftor (ZINC000064033452) complex. The hydrogen bonds formed (yellow dotted lines), the distance in Å of these interactions, and the residues that interact with the drug or are part of the binding site were highlighted. <i>Microbiol Immunol: 68:414-426</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"68 12","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prevalence and Comparative Analysis of Adhesion and Biofilm-Related Genes in Staphylococcus aureus Isolates: A Network Meta-Analysis","authors":"Aram Sharifi,&nbsp;Peyman Mahmoudi,&nbsp;Keyvan Sobhani,&nbsp;Morahem Ashengroph","doi":"10.1111/1348-0421.13189","DOIUrl":"10.1111/1348-0421.13189","url":null,"abstract":"<p><i>Staphylococcus aureus</i> is a versatile pathogen capable of causing a wide range of infections, from minor skin infections to life-threatening invasive diseases. The pathogenicity of <i>S. aureus</i> is attributed to its ability to produce various virulence factors, including adhesion and biofilm-related proteins. Understanding the prevalence and distribution of these genes among <i>S. aureus</i> isolates from different sources is crucial for devising effective strategies to combat biofilm-associated contamination. In this study, we conducted a comprehensive network meta-analysis to assess the prevalence of adhesion and biofilm-related genes in <i>S. aureus</i> isolates and investigate the impact of the isolate source on their occurrence. A systematic search of multiple databases was performed, and a total of 53 relevant studies were included. The prevalence of adhesion and biofilm-related genes in <i>S. aureus</i> isolates was determined, with the highest prevalence observed for <i>clfB</i> (<i>p</i>-estimate = 85.4, 95% confidence interval [CI] 78–90.6), followed by <i>eno</i> (<i>p</i>-estimate = 81.1, 95% CI 61.7–91.9), and <i>icaD</i> (<i>p</i>-estimate = 77, 95% CI 68.6–83.6). Conversely, <i>bap</i> and <i>bbp</i> genes exhibited the lowest prevalence rates (<i>p</i>-estimate = 6.7 and 18.7, respectively). The network meta-analysis allowed us to examine the pairwise co-study of adhesion and biofilm-related genes in <i>S. aureus</i> isolates. The most frequently co-studied gene pairs were <i>icaA</i>-<i>icaD</i> (30 times) and <i>fnbA</i>-<i>fnbB</i> (25 times). Subgroup analysis showed that the occurrence of <i>icaC</i> and <i>icaB</i> genes was significantly lower in animal isolates compared to human and food isolates (<i>p</i> &lt; 0.05). It is worth noting that there was limited data available for the analysis of <i>sasG</i>, <i>bbp</i>, <i>bap</i>, <i>eno</i>, and <i>fib</i> genes. In conclusion, the study revealed varying prevalence rates of adhesion and biofilm-related genes in <i>S. aureus</i> isolates. Genes such as <i>clfB</i>, <i>eno</i>, and <i>icaD</i> were found to be highly prevalent, while <i>bap</i> and <i>bbp</i> were less common. Limited existing data on the prevalence of genes like <i>sasG</i>, <i>bbp</i>, <i>bap</i>, <i>eno</i>, and <i>fib</i> highlights the need for further research to determine their exact prevalence rates. Our results contribute to a better understanding of <i>S. aureus</i> pathogenesis and can facilitate the development of effective strategies for the prevention and treatment of <i>S. aureus</i> infections.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 2","pages":"104-113"},"PeriodicalIF":1.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of Replication-Competent Hepatitis B Virus Harboring Tagged Polymerase for Visualization and Quantification of the Infection","authors":"Chiharu Morita,&nbsp;Masami Wada,&nbsp;Eriko Ohsaki,&nbsp;Shihoko Kimura-Ohba,&nbsp;Keiji Ueda","doi":"10.1111/1348-0421.13183","DOIUrl":"10.1111/1348-0421.13183","url":null,"abstract":"<p>Hepatitis B virus (HBV) infection is a serious global health problem causing acute and chronic hepatitis and related diseases. Approximately, 296 million patients have been chronically infected with the virus, leading to cirrhosis and hepatocellular carcinoma. Although HBV polymerase (HBVpol, pol) plays a pivotal role in HBV replication and must be a definite therapeutic target. The problems are that the detailed functions and intracellular dynamics of HBVpol remain unclear. Here, we constructed two kinds of tagged HBVpol, PA-tagged and HiBiT-tagged pol, and the HBV-producing vectors. Each PA tag and HiBiT tag were inserted into N-terminus of spacer region on HBVpol open reading frame. Transfection of the plasmids into HepG2 cells led to production of HBV. These tagged HBVpol were detectable in HBV replicating cells and pol-HiBiT enabled quantitative analysis. Furthermore, these recombinant HBV were infectious to primary human hepatocytes. Thus, we successfully designed infectious and replication-competent recombinant HBV harboring detectable tagged HBVpol. Such infectious recombinant HBV will provide a novel tool to study HBVpol dynamics and develop new therapeutics against HBV.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 1","pages":"43-58"},"PeriodicalIF":1.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota and Metabolite Profiles Associated With Functional Constipation Severity","authors":"Jiwei Wang,&nbsp;Jixin He,&nbsp;Dandan Liu,&nbsp;Tao Zhang,&nbsp;Yin Wu,&nbsp;Ming Xie","doi":"10.1111/1348-0421.13187","DOIUrl":"10.1111/1348-0421.13187","url":null,"abstract":"<p>Functional constipation (FC) is a common digestive disorder that affects patients' quality of life and is closely associated with intestinal tumors. This study used a cross-sectional design to assess the changes of intestinal flora and metabolites in different severities of FC patients through 16S rRNA sequencing and metabolomics analysis. Results showed that patients with severe FC had significantly higher clinical and anxiety scores compared to those in the mild and moderate groups. The species richness of intestinal microorganisms in the severe FC group was also significantly higher, and obvious differences in the flora composition existed. Specifically, the <i>Bacteroidota</i> was more abundant in the severe FC group, which was a characteristic feature distinguishing severe FC. Metabolomic analyses also revealed metabolite differences among patients with mild-to-moderate and severe FC, with the severe FC group showing increased enrichment in L-isoleucine biosynthesis and glycolysis metabolic pathways. The short-chain fatty acid–targeted metabolome suggested that a decrease in butyric acid might be related to worsening constipation. This study suggests that specific flora and metabolic pathways could serve as potential diagnostic and therapeutic targets, thereby contributing to the development of new diagnostic and therapeutic approaches to improve the quality of life and therapeutic outcomes for FC patients.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 2","pages":"85-95"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RpoB H481Y Rifampicin Resistance Mutation-Associated Oxidative Stress Sensitivity Reduces the Virulence of Staphylococcus aureus","authors":"Tomonori Kano,&nbsp;Kazuya Ishikawa,&nbsp;Lina Imai,&nbsp;Kazuyuki Furuta,&nbsp;Chikara Kaito","doi":"10.1111/1348-0421.13190","DOIUrl":"10.1111/1348-0421.13190","url":null,"abstract":"<p>In this study, we have established a <i>Staphylococcus aureus</i> RpoB H481Y mutant strain and demonstrated that it is sensitive to menadione or hydrogen peroxide-induced oxidative stress and exhibits reduced virulence against a silkworm infection model. Furthermore, the reduced virulence of the RpoB H481Y mutant was abrogated in the presence of <i>N</i>-acetylcysteine, a reactive oxygen species scavenger. These results suggest that oxidative stress sensitivity caused by the RpoB H481Y rifampicin resistance mutation attenuates the virulence of <i>S. aureus</i>.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 2","pages":"128-131"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decade-Long Analysis of Trends in Antimicrobial Resistance in a Neurosurgical Hospital in Kathmandu, Nepal","authors":"Ajaya Basnet,&nbsp;Apurba Shrestha,&nbsp;Gopal Raman Sharma,&nbsp;Shila Shrestha,&nbsp;Laxmi Kant Khanal,&nbsp;Junu Richhinbung Rai,&nbsp;Rajendra Maharjan,&nbsp;Bijaya Basnet,&nbsp;Shiba Kumar Rai","doi":"10.1111/1348-0421.13185","DOIUrl":"10.1111/1348-0421.13185","url":null,"abstract":"<div>\u0000 \u0000 <p>Multidrug-resistant (MDR) bacteria cause infections with higher risks of morbidity, mortality, and financial burden. Understanding the antimicrobial resistance patterns of these pathogens is crucial for effective treatment and managing resistance. Therefore, this retrospective study examined the prevalence, causes, and trends in antimicrobial resistance in bacterial infections at a neurosurgical hospital in Nepal. We analyzed the demographics, bacteriological profiles, and antimicrobial susceptibility results in patients who visited Dirghayu Guru Hospital and Research Center, Kathmandu, Nepal, between January 2014 and January 2024, using SPSS, version 17.00. Among 4758 patients, 465 (9.77%) had infections caused by 571 bacteria. Of them, 435 (93.55%) patients had urinary tract infections, 89 (19.14%) had bloodstream infections, and 31 (6.67%) had respiratory tract infections. <i>Klebsiella pneumoniae</i> (n = 172, 30.12%) was the predominant bacteria. Proportions of drug-resistant Enterobacterales and gram-positive cocci among drug-resistant bacteria against tetracyclines were 83.33% and 45.83%, cephalosporins were 78.02% and 40.45%, quinolones were 72.25% and 50.00%, aminoglycosides were 65.14% and 43.53%, carbapenems were 62.96% and 30.00%, penicillins were 54.55% and 57.89%, and penicillin with beta-lactamase inhibitors (PwBLIs) were 40.54% and 42.31%, respectively. Proportions of drug-resistant nonfermenters among drug-resistant bacteria showed 100.00% resistance to these antimicrobials. MDR isolates (<i>n</i> = 118, 20.67%) were 100.00% susceptible to piperacillin–tazobactam and 83.33% to polymyxin B. Over the years, resistance increased for cephalosporins (48.15%–60.53%) but decreased for carbapenems (50.00%–33.33%), penicillins (64.29%–42.31%), PwBLIs (50.00%–12.50%), aminoglycosides (60.00%–49.12%), tetracyclines (100.00%–16.67%), and polymyxins (76.22%–16.67%). One-tenth of hospital-visiting patients had bacterial infections, with three-fourths involving Enterobacterales and one-fifth involving MDR bacteria. In recent years, resistance to cephalosporins has increased, whereas resistance to other beta-lactams, aminoglycosides, and polymyxins has decreased.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 1","pages":"10-24"},"PeriodicalIF":1.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}