Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Advancements in the development of antivirals against SARS-Coronavirus.","authors":"Mrityunjay Kumar, Mirza Sarwar Baig, Kanchan Bhardwaj","doi":"10.3389/fcimb.2025.1520811","DOIUrl":"10.3389/fcimb.2025.1520811","url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1520811"},"PeriodicalIF":4.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomic next-generation sequencing for lung cancer low respiratory tract infections diagnosis and characterizing microbiome features.","authors":"Yao Liu, Bohan Yang, Qi Qi, Shijie Liu, Yiheng Du, Linlin Ye, Qiong Zhou","doi":"10.3389/fcimb.2024.1518199","DOIUrl":"10.3389/fcimb.2024.1518199","url":null,"abstract":"<p><strong>Background: </strong>The capability of mNGS in diagnosing suspected LRTIs and characterizing the respiratory microbiome in lung cancer patients requires further evaluation.</p><p><strong>Methods: </strong>This study evaluated mNGS diagnostic performance and utilized background microbial sequences to characterize LRT microbiome in these patients. GSVA was used to analyze the potential functions of identified genera.</p><p><strong>Results: </strong>Bacteria were the most common pathogens (n=74) in LRTIs of lung cancer patients, and polymicrobial infections predominated compared to monomicrobial infections (p<0.001). In diagnosing LRTIs in lung cancer patients, the pathogen detection rate of mNGS (83.3%, 70/84) was significantly higher than that of sputum culture (34.5%, 29/84) (p<0.001). This result was consistent with that of non-lung cancer patients (p<0.001). Furthermore, in the specific detection of bacteria (95.7% vs. 22.6%) and fungi (96.0% vs. 22.2%), the detection rate of mNGS was also significantly higher than that of CMTs mainly based on culture (p<0.001, p<0.001). However, in the detection of CMV/EBV viruses, there was no significant difference between the detection rate of mNGS and that of viral DNA quantification (p = 1.000 and 0.152). mNGS analysis revealed <i>Prevotella</i>, <i>Streptococcus</i>, <i>Veillonella</i>, <i>Rothia</i>, and <i>Capnocytophaga</i> as the most prevalent genera in the LRT of lung cancer patients. GSVA revealed significant correlations between these genera and tumor metabolic pathways as well as various signaling pathways including PI3K, Hippo, and p53.</p><p><strong>Conclusion: </strong>mNGS showed a higher pathogen detection rate than culture-based CMTs in lung cancer patients with LRTIs, and also characterizing LRT microbiome composition and revealing potential microbial functions linked to lung carcinogenesis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1518199"},"PeriodicalIF":4.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of the oral pathogen <i>Filifactor alocis</i> and its FtxA toxin related to clinical parameters and presence of <i>Aggregatibacter actinomycetemcomitans</i>.","authors":"Zeinab Razooqi, Nabil Khzam, Mahina L'Hostis, Georgios N Belibasakis, Anders Johansson, Jan Oscarsson","doi":"10.3389/fcimb.2024.1501028","DOIUrl":"10.3389/fcimb.2024.1501028","url":null,"abstract":"<p><p>The Gram-positive organism <i>Filifactor alocis</i> is implicated in multiple oral diseases including periodontitis, and approximately 50% of known strains encode and produce a recently identified repeat-in-toxin (RTX) protein, FtxA, partly homologous to the <i>Aggregatibacter actinomycetemcomitans</i> leukotoxin. By assessing a longitudinal Ghanaian study population of adolescents, we recently identified a possible correlation between <i>F. alocis</i> levels, <i>ftxA</i> gene carriage, and progression of clinical attachment loss (CAL). To extend knowledge on the possible significance of <i>F. alocis</i> and its FtxA in periodontal disease, we have in the present work analyzed saliva samples in an independent cohort of periodontitis (n=156), collected at two private periodontal specialist practices in Perth, Western Australia. The present results corroborate that high loads of <i>F. alocis</i> and the presence of its <i>ftxA</i> gene together are associated with parameters of periodontal tissue destruction and severity. Moreover, among the individuals carrying <i>A. actinomycetemcomitans</i>, a majority also exhibited an <i>ftxA</i>-positive <i>F. alocis</i>, supporting the notion of the synergistic behavior of these two species. This emphasizes that <i>F. alocis</i> and its <i>ftxA</i> are involved in the pathogenesis of periodontitis and may have ecological roles, with diagnostic and prognostic implications for the disease.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1501028"},"PeriodicalIF":4.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid diagnostic testing combined with an immediate infectious disease consultation increases the rate of septic intensive care unit patients on targeted antibiotic therapy.","authors":"Evelyn Kramme, Nadja Käding, Tobias Graf, Karolin Schmoll, Heidi Linnen, Katharina Nagel, Esther Grote-Levi, Susanne Hauswaldt, Dennis Nurjadi, Jan Rupp","doi":"10.3389/fcimb.2024.1513408","DOIUrl":"10.3389/fcimb.2024.1513408","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the impact of rapid diagnostic testing (RDT) combined with immediate infectious disease (ID) consultation on the treatment of septic patients with positive blood cultures in intensive care units in a setting without 24/7 service.</p><p><strong>Methods: </strong>Adult ICU patients in a tertiary care hospital with positive blood cultures were included from January 2019 to December 2020. The control group underwent routine laboratory testing, and for the intervention group, RDT was applied with immediate ID consultation.</p><p><strong>Results: </strong>In 77 out of the 91 patients in the intervention group, the pathogen was identified by RDT. Regarding antimicrobial susceptibility testing (AST), genotypic testing (ePlex^®) was successful for Gram-positive cocci, but inadequate for Gram-negative rods. Phenotypic resistance testing with the Accelerate PhenoTest^® took too long to be successfully integrated into the intervention. Adaptation of empirical antibiotic therapy was recommended for 72.7% of the patients. Adherence to the ID consultation post-RDT results was high at 82.3%. In the control group, adaptation of the initial antibiotic therapy would have been recommended for 81.8% of patients, if the species identification had been available. Overall adherence to the local antibiotic therapy guideline for sepsis was significantly lower in the control than in the intervention group (27.8% versus 89.3%, p<0.001).</p><p><strong>Conclusion: </strong>Integration of an RDT system in the microbiological workflow for septic patients in ICU combined with a standardized ID intervention led to a significantly higher percentage of adequate antimicrobial treatment and greater adherence to local antibiotic therapy recommendations, even in a setting where 24/7 service is not available.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1513408"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the <i>Vibrio anguillarum Va</i>RyhB regulon and role in pathogenesis.","authors":"Yingjie Li, Xinran Yu, Peng Li, Xin Li, Lushan Wang","doi":"10.3389/fcimb.2024.1531176","DOIUrl":"10.3389/fcimb.2024.1531176","url":null,"abstract":"<p><strong>Background: </strong>The marine Gram-negative bacterium <i>Vibrio anguillarum</i> is one of the major pathogens in aquaculture. Iron uptake is a prerequisite for virulence and is strictly controlled by a global iron uptake regulator, Fur, which acts as a repressor under iron-replete conditions. When iron is depleted, Fur also functions as an activator, playing an important role in pathogenesis. It is unclear whether this upregulation model is mediated by a small RNA, RyhB.</p><p><strong>Methods: </strong>The small RNA, <i>VaryhB</i>, was deleted in <i>V. anguillarum</i> strain 775, and its regulon was investigated using transcriptomic analysis. The roles of VaRyhB in siderophore synthesis, chemotaxis and motility, and oxidative stress were evaluated using chrome azurol S (CAS) liquid assay, swimming motility assay, and intracellular reactive oxygen species (ROS) assay, respectively. The virulence of VaRyhB was evaluated by challenging turbot larvae intraperitoneally.</p><p><strong>Results: </strong>The small RNA called VaRyhB identified in <i>V. anguillarum</i> strain 775 is significantly longer than that in Escherichia coli. Transcriptomic analysis revealed that VaRyhB is critical for iron homeostasis under limited iron conditions, and deletion of VaRyhB resulted in lower expression levels of certain genes for siderophore biosynthesis and transport, thereby leading to impaired growth, reduced siderophore production, and decreased pathogenesis. The virulence factor motility is also upregulated by VaRyhB, and reduced motility capability was observed in the ΔVaryhB mutant, which may be another reason resulting in weak pathogenesis. The sensitivity toward H2O2 in the ΔVafur mutant could be restored by the loss of VaRyhB, suggesting that the role of Fur in oxidative stress is mediated by VaRyhB. VaRyhB also functions to inhibit the expression of genes involved in Fe-S assembly and the TCA cycle. In addition, two aspects of the type VI secretion system and molybdenum cofactor biosynthesis were first identified as being regulated by VaRyhB.</p><p><strong>Conclusion: </strong>In <i>V. anguillarum</i>, the sRNA VaRyhB plays a critical role in the inhibition of genes involved in the TCA cycle, Fe-S assembly, and the type VI secretion system. It is also essential for the activation of siderophore synthesis, chemotaxis and motility, and anaerobic denitrification. Our work provides the first evidence of the VaRyhB regulon and its role in the pathogenesis of <i>V. anguillarum</i>.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1531176"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAM/TMA-DPH as a promising alternative to SYTO9/PI for cell viability assessment in bacterial biofilms.","authors":"Tinatini Tchatchiashvili, Mateusz Jundzill, Mike Marquet, Kamran A Mirza, Mathias W Pletz, Oliwia Makarewicz, Lara Thieme","doi":"10.3389/fcimb.2024.1508016","DOIUrl":"10.3389/fcimb.2024.1508016","url":null,"abstract":"<p><strong>Introduction: </strong>Accurately assessing biofilm viability is essential for evaluating both biofilm formation and the efficacy of antibacterial treatments. Traditional SYTO9 and propidium iodide (PI) live/dead staining in biofilm viability assays often ace challenges due to non-specific staining, limiting precise differentiation between live and dead cells. To address this limitation, we investigated an alternative staining method employing calcein acetoxymethyl (CAM) to detect viable cells based on esterase activity, and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH) to assess the remaining biofilm population.</p><p><strong>Methods: </strong>Biofilms of <i>Pseudomonas aeruginosa, Klebsiella pneumoniae</i>, <i>Staphylococcus aureus</i>, and <i>Enterococcus faecium</i> were matured and exposed to varying concentrations of antibiotics or sterile medium. Biofilm viability was assessed using CAM/TMA-DPH or SYTO9/PIstaining, followed by analysis with confocal laser scanning microscopy (CLSM) and ImageJ-based biofilm surface coverage quantification. Viability findings were compared with colony-forming units (CFU/mL), a standard microbial viability measure.</p><p><strong>Results: </strong>CAM/TMA-DPH staining demonstrated strong positive correlations with CFU counts across all bacterial species (<i>r</i> = 0.59 - 0.91), accurately reflecting biofilm vitality. In contrast, SYTO9/PI staining consistently underestimated the viability of untreated biofilms, particularly in <i>Klebsiella pneumoniae</i>, where a negative correlation with CFU/mL was observed (<i>r</i> = -0.04). Positive correlations for SYTO9/PI staining were noted in other species (<i>r</i> = 0.65 - 0.79). These findings underscore the limitations of membrane integrity-based staining methods and highlight the advantages of metabolic-based probes like CAM/TMA-DPH.</p><p><strong>Discussion: </strong>Our findings suggest that CAM/TMA-DPH staining provides a promising alternative to SYTO9/PI for cell viability assessment in bacterial biofilms, highlighting the advantages of metabolic-based probes over traditional membrane integrity assays. The consistency of CAM/TMA-DPH staining across different bacterial species underscores its potential to advance studies on biofilm and contribute to the development of more effective anti-biofilm treatments, which is essential for clinical management of biofilm-associated infections.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1508016"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding <i>MexB</i> efflux pump genes: structural, molecular, and phylogenetic analysis of multidrug-resistant and extensively drug-resistant <i>Pseudomonas aeruginosa</i>.","authors":"Muhammad Bilal Habib, Naseer Ali Shah, Afreenish Amir, Huda Ahmed Alghamdi, Muhammad Haseeb Tariq, Kiran Nisa, Mariam Ammoun","doi":"10.3389/fcimb.2024.1519737","DOIUrl":"10.3389/fcimb.2024.1519737","url":null,"abstract":"<p><strong>Objective: </strong>Emerging drug resistance in <i>Pseudomonas aeruginosa</i> is of great concern in clinical settings. <i>P. aeruginosa</i> activates its efflux-pump system in order to evade the effect of antibiotics. The current investigation aims to detect <i>MexB</i> genes in <i>P. aeruginosa</i>, their structural and molecular analysis and their impact on antimicrobial susceptibility profiling.</p><p><strong>Methods: </strong>A total of 42 clinical specimens were aseptically collected from hospitalized patients who had underlying infections related to medical implants. Matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) were used for the identification of isolates. The methods used in this study were antibiotic susceptibility profiling, minimum inhibitory concentration (MIC), polymerase chain reaction (PCR), sanger sequencing, phylogenetic analysis, MolProbity score, Ramachandran plot analysis and multiple sequence alignment.</p><p><strong>Results: </strong>The highest resistance was shown by <i>P. aeruginosa</i> against cefoperazone (67%), gentamycin and amikacin (66%) each, followed by cefotaxime (64%). The prevalence of multi-drug resistant (MDR) and extensively drug resistant (XDR) was 57% and 12%, respectively. The presence of an active efflux-pump system was indicated by the <i>MexB</i> genes found in most of the resistant isolates (p<0.05). Following addition of efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a significant decrease (p<0.05) in MIC was observed in resistance, that revealed the presence of active efflux pump system. Phylogenetic analysis revealed evolutionary relationships with the <i>P. aeruginosa</i> strains isolated in Switzerland, Denmark and Germany. Protein domain architecture revealed that <i>MexB</i> gene proteins were involved in particular efflux pump function. Protein sequences aligned by multiple sequence alignment revealed conserved regions and sequence variants, which suggested antibiotic translocation and evolutionary divergence. These highly conserved regions could be used for diagnostic purposes of efflux pump <i>MexB</i> genes.</p><p><strong>Conclusion: </strong>To avoid their spread in hospital settings, responsible authorities ought to begin rigorous initiatives in order to reduce the prevalence of multi-drug resistant, extensively drug resistant, and efflux pump carrying isolates in clinical settings.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1519737"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of lower respiratory microbiota in children's refractory <i>Mycoplasma pneumoniae</i> pneumonia pre- and post-COVID-19 era.","authors":"Zhimin Xi, Jinglong Chen, Libo Wang, Aizhen Lu","doi":"10.3389/fcimb.2024.1438777","DOIUrl":"10.3389/fcimb.2024.1438777","url":null,"abstract":"<p><strong>Introduction: </strong>Little was known about the characteristics of low respiratory tract (LRT) microbiota of refractory <i>M. pneumoniae</i> pneumonia (RMPP) in children before and after the COVID-19 pandemic.</p><p><strong>Methods: </strong>Forty-two children diagnosed with RMPP in 2019 (Y2019 group) and 33 children diagnosed with RMPP in 2023 (Y2023 group), entered into the study. The characteristics of the clinical findings were examined, and the LRT microbiota was analyzed by metagenomic next generation sequencing.</p><p><strong>Results: </strong>The ratio of consolidate, atelectasis, lung necrosis, and erythema multiforme in Y2023 group was significantly higher than that in Y2019 (<i>P</i><0.05). <i>Mycoplasmoides pneumoniae</i> was the top species of the LRT microbiota in both groups. The rate of macrolide resistance MP in Y2023 was significantly higher than that in Y2019 (<i>P</i><0.05), and the mutant site was all 23S rRNA A2063G. There were no significant differences in α-diversity and β-diversity of LRT microbiota between Y2019 and Y2023 group. <i>Trichoderma citrinoviride, Canine mastadenovirus A, Ralstonia pickettii, Lactococcus lactis, Pseudomonas aeruginosa</i> were the biomarkers of LRT microbiota in children with RMPP of Y2023. The abundance of <i>Mycoplasmoides pneumoniae</i> positively correlated with the levels of D-dimer and LDH, negatively correlated with the counts of CD3⁺ T cells, CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells.</p><p><strong>Discussion: </strong>Our study showed that high abundance of MP was correlated with the severity of RMPP and decrease of immune cells. <i>Trichoderma citrinoviride, Canine mastadenovirus A, Ralstonia pickettii, Lactococcus lactis, Pseudomonas aeruginosa</i> were the biomarkers in microbiota of LRT in children with RMPP post COVID-19 era.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1438777"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding mitochondrial DNA damage and repair associated with <i>H. pylori</i> infection.","authors":"Aashirwad Shahi, Dawit Kidane","doi":"10.3389/fcimb.2024.1529441","DOIUrl":"10.3389/fcimb.2024.1529441","url":null,"abstract":"<p><p>Mitochondrial genomic stability is critical to prevent various human inflammatory diseases. Bacterial infection significantly increases oxidative stress, driving mitochondrial genomic instability and initiating inflammatory human disease. Oxidative DNA base damage is predominantly repaired by base excision repair (BER) in the nucleus (nBER) as well as in the mitochondria (mtBER). In this review, we summarize the molecular mechanisms of spontaneous and <i>H. pylori</i> infection-associated oxidative mtDNA damage, mtDNA replication stress, and its impact on innate immune signaling. Additionally, we discuss how mutations located on mitochondria targeting sequence (MTS) of BER genes may contribute to mtDNA genome instability and innate immune signaling activation. Overall, the review summarizes evidence to understand the dynamics of mitochondria genome and the impact of mtBER in innate immune response during <i>H. pylori</i>-associated pathological outcomes.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1529441"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome sequencing reveals transmission pattern and drug resistance of <i>Mycobacterium tuberculosis</i> intra- or inter-hosts.","authors":"Feng Ding, Wanfei Liu, Chi Wu, Wensi Zhang, Shuyan Chen, Wenjie Lai, Jiayao Qu, Qiang Lin, Shuihua Lu, Jiuxin Qu","doi":"10.3389/fcimb.2024.1488547","DOIUrl":"10.3389/fcimb.2024.1488547","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a serious global public health problem. The <i>Mycobacterium tuberculosis</i> (MTB) is responsible for approximately 10 million new TB cases globally each year. This study aimed to investigate transmission pattern and drug resistance of MTB in Shenzhen, China.</p><p><strong>Methods: </strong>A retrospective study on 286 samples from 184 TB patients collected between 2015 and 2018 in Shenzhen Third People's Hospital was conducted using whole-genome sequencing. Drug susceptibility testing (DST) was performed using both phenotypic DST (pDST) and molecular DST (mDST). Sample diversity was evaluated by SNPs and transmission clusters were identified based on SNP differences of 12 or fewer in genetic clusters.</p><p><strong>Results: </strong>Except four samples identified as non-tuberculous mycobacteria, 282 MTB samples (181 patients) underwent mDST, with 244 samples (162 patients) undergoing pDST. The overall multidrug-resistant rate in patients was 22.31% in pDST (12.00% for new patients and 40.82% for retreatment patients) and 34.48% in mDST (20.41% for new patients and 58.21% for retreatment patients). Totally 92 transmission clusters were identified, encompassing 70.21% samples (57.46% patients), with 5 clusters containing samples (15, 5.32%) from different patients (9, 4.97%), indicating recent transmission. The drug-resistant mutations in 36 of 45 transmission clusters (80.00%) were identical in all samples, suggesting the transmission of drug resistance. Patients with multiple samples were categorized into simultaneous sampling (SS) and continuous sampling (CS) groups, revealing significant differences in treatment types, treatment outcomes, residential addresses, and drug resistance types. mDST showed greater accuracy than pDST in SS and CS groups. A novel method based on heterozygous SNPs and two-sample Kolmogorov-Smirnov test were developed and identified 12 (4.26%) samples as mixed infection samples. Six of 12 patients had mixed and pure samples together, and major strains of mixed samples were closer to corresponding pure strains than minor strains.</p><p><strong>Conclusions: </strong>This retrospective study, conducted at the only municipal hospital specializing in infectious diseases in Shenzhen, provides the opportunity to understand drug resistance of TB patients, which mainly are refractory patients. The study revealed transmission patterns of MTB, analyzed mixed infections, and tracked changes in MTB strains during short/long-term treatment.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1488547"},"PeriodicalIF":4.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}