Microbiology spectrum最新文献

{"title":"Comparison of the mechanism of antimicrobial action of the gold(I) compound auranofin in Gram-positive and Gram-negative bacteria.","authors":"Laísa Quadros Barsé, Agnes Ulfig, Marharyta Varatnitskaya, Melissa Vázquez-Hernández, Jihyun Yoo, Astrid M Imann, Natalie Lupilov, Marina Fischer, Katja Becker, Julia E Bandow, Lars I Leichert","doi":"10.1128/spectrum.00138-24","DOIUrl":"10.1128/spectrum.00138-24","url":null,"abstract":"<p><p>While highly effective at killing Gram-positive bacteria, auranofin lacks significant activity against Gram-negative species for reasons that largely remain unclear. Here, we aimed to elucidate the molecular mechanisms underlying the low susceptibility of the Gram-negative model organism <i>Escherichia coli</i> to auranofin when compared to the Gram-positive model organism <i>Bacillus subtilis</i>. The proteome response of <i>E. coli</i> exposed to auranofin suggests a combination of inactivation of thiol-containing enzymes and the induction of systemic oxidative stress. Susceptibility tests in <i>E. coli</i> mutants lacking proteins upregulated upon auranofin treatment suggested that none of them are directly involved in <i>E. coli</i>'s high tolerance to auranofin. <i>E. coli</i> cells lacking the efflux pump component TolC were more sensitive to auranofin treatment, but not to an extent that would fully explain the observed difference in susceptibility of Gram-positive and Gram-negative organisms. We thus tested whether <i>E. coli</i>'s thioredoxin reductase (TrxB) is inherently less sensitive to auranofin than TrxB from <i>B. subtilis</i>, which was not the case. However, <i>E. coli</i> strains lacking the low-molecular-weight thiol glutathione, but not glutathione reductase, showed a high susceptibility to auranofin. Bacterial cells expressing the genetically encoded redox probe roGFP2 allowed us to observe the oxidation of cellular protein thiols <i>in situ</i>. Based on our findings, we hypothesize that auranofin leads to a global disturbance in the cellular thiol redox homeostasis in bacteria, but Gram-negative bacteria are inherently more resistant due to the presence of drug export systems and high cellular concentrations of glutathione.IMPORTANCEAuranofin is an FDA-approved drug for the treatment of rheumatoid arthritis. However, it has also high antibacterial activity, in particular against Gram-positive organisms. In the current antibiotics crisis, this would make it an ideal candidate for drug repurposing. However, its much lower activity against Gram-negative organisms prevents its broad-spectrum application. Here we show that, on the level of the presumed target, there is no difference in susceptibility between Gram-negative and Gram-positive species: thioredoxin reductases from both <i>Escherichia coli</i> and <i>Bacillus subtilis</i> are equally inhibited by auranofin. In both species, auranofin treatment leads to oxidative protein modification on a systemic level, as monitored by proteomics and the genetically encoded redox probe roGFP2. The single largest contributor to <i>E. coli</i>'s relative resistance to auranofin seems to be the low-molecular-weight thiol glutathione, which is absent in <i>B. subtilis</i> and other Gram-positive species.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an infant colon simulating <i>in vitro</i> model, I-TIM-2, to study the effects of modulation strategies on the infant gut microbiome composition and function.","authors":"Olivia Colberg, Gerben D A Hermes, Tine Rask Licht, Anita Wichmann, Adam Baker, Martin Frederik Laursen, Anja Wellejus","doi":"10.1128/spectrum.00724-24","DOIUrl":"10.1128/spectrum.00724-24","url":null,"abstract":"<p><p>The early life stages are critical for the development of the gut microbiome. Variables such as antibiotics exposure, birth-mode via Cesarean section, and formula feeding are associated with disruptions in microbiome development and are related to adverse health effects later in life. Studying the effects of microbiome-modulating strategies in infants is challenged by appropriate ethical constraints. Therefore, we developed I-TIM-2, an infant <i>in vitro</i> colonic model based on the validated, computer-controlled, dynamic model of the colon, TIM-2. The system, consisting of four separate compartments, was inoculated with feces from four healthy, primarily breastfed infants, displaying distinctive microbiome profiles. For each infant's fecal sample, a 96-h experiment was performed, with two compartments receiving an infant diet adapted medium and two compartments additionally receiving five human milk oligosaccharides (HMOs) in physiological concentrations and proportions. Bacterial composition was determined by shotgun metagenomics and qPCR. Concentrations of short-chain fatty acids (SCFAs) and HMOs were determined by LC-MS. Microbial diversity and high amounts of inoculum-derived species were preserved in the model throughout each experiment. Microbiome composition and SCFA concentrations were consistent with published data from infants. HMOs strongly modulated the microbiome composition by stimulating relative proportions of <i>Bifidobacterium</i>. This affected the metabolic output and resulted in an increased production of acetic and formic acid, characteristic of bifidobacterial HMO metabolism. In conclusion, these data demonstrate the development of a valid model to study the dynamics and modulations of the infant gut microbiome and metabolome.IMPORTANCEThe infant gut microbiome is intricately linked to the health of its host. This is partly mediated through the bacterial production of metabolites that interact with the host cells. Human milk shapes the establishment of the infant gut microbiome as it contains human milk sugars that select for primarily bifidobacteria. The establishment can be disrupted by modern interventions such as formula feeding. This can alter the microbiome composition and metabolite production profile, which can affect the host. In this article, we set up an infant <i>in vitro</i> colonic model to study microbiome interactions and functions. In this model, we investigated the effects of human milk sugars and their promotion of bifidobacteria at the expense of other bacteria. The model is an ideal system to assess the effects of various modulating strategies on the infant gut microbiome and its interactions with its host.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization and clinical evaluation of prosthetic joint infections caused by <i>Cutibacterium acnes</i>.","authors":"C Liew-Littorin, S Davidsson, Å Nilsdotter-Augustinsson, B Hellmark, H Brüggemann, B Söderquist","doi":"10.1128/spectrum.00303-24","DOIUrl":"10.1128/spectrum.00303-24","url":null,"abstract":"<p><p><i>Cutibacterium acnes</i> is a major skin commensal that may act as an opportunistic pathogen. It is difficult to interpret findings of <i>C. acnes</i> in tissue cultures obtained during arthroplasty revision surgery, since they may represent true infection or contamination. This study investigated whether <i>C. acnes</i> obtained from prosthetic joint infections (PJIs) were related and shared common genomic traits that might correlate with clinical courses and patient outcomes. <i>C. acnes</i> isolates from revision surgery of patients with PJIs of the hip, shoulder, and knee were characterized using molecular methods to determine the sequence type (ST) and the presence of possible virulence determinants (Christie-Atkins-Munch-Peterson factors, dermatan sulfate-binding adhesion 1, hyaluronidase lyase, and linear plasmid). A standardized review of the patients' medical charts was performed. The study included 37 patients with <i>C. acnes</i> culture-positive tissue samples where multiple isolates of <i>C. acnes</i> belonged to the same ST. Most of the isolates belonged to phylotype IA₁. Phylogenetic analysis of virulence determinants revealed no shared pattern among PJI isolates. Seven patients had a polymicrobial infection. Exchange revision was performed in 70% of the patients, and >50% of all patients received antibiotic treatment for ≥3 months. Failure was noted in seven patients. No specific ST or any identifiable unique feature among virulence determinants were found among <i>C. acnes</i> isolated from PJIs of hips and shoulders. The majority of patients had low inflammatory markers and were treated successfully, even polymicrobial infections. However, failure was more common among shoulder infections compared with hip infections.</p><p><strong>Importance: </strong>Prosthetic joint infection (PJI) is a rare complication after arthroplasty surgery. The infection seldom resolves without a combination of both surgical and antibiotic treatment and can cause significant suffering among affected patients. <i>Cutibacterium acnes</i> is a common skin bacterium that is most often found in shoulder PJIs but can also infect other prostheses. In this study, we conducted a review of patients with previously verified PJIs involving <i>C. acnes</i> in hip or shoulder prostheses, along with a genomic analysis of the bacteria causing the infections. The majority of patients had successful outcomes. We did not identify any specific phylogenetic lineage or specific molecular signature of virulence factors among these PJI-associated <i>C. acnes</i> isolates that seemed to be associated with increased potential to cause infection among this species. This indicates that <i>C. acnes</i> isolated from PJIs originates from the patients' own skin microbiome and is inoculated during the arthroplasty surgery.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a droplet digital PCR assay for the detection of BK polyomavirus.","authors":"Lu Ai, Yating Zhao, Chianru Tan, Lu Bai, Gang Huang, Ruizhi Wang, Hao Huang, Xuegao Yu, Yong Guo, Peisong Chen","doi":"10.1128/spectrum.01089-24","DOIUrl":"10.1128/spectrum.01089-24","url":null,"abstract":"<p><p>The objective of this study was to establish a more sensitive and specific diagnostic method for detecting plasma BK polyomavirus (BKPyV) DNA load in patients after renal transplantation using droplet digital polymerase chain reaction (ddPCR) and to validate the methodology. The linear range, lower limit of detection, accuracy, precision, and specificity of the detection system were evaluated by using the WHO BKPyV standard (7.2 log₁₀ IU/mL) as a reference, in accordance with the relevant documents of the Clinical and Laboratory Standards Institute. Plasma samples were collected from 74 renal transplantation patients with urinary BKPyV-DNA levels exceeding 7 log₁₀ copies/mL. Quantitative PCR (qPCR) and ddPCR were performed, and their diagnostic efficacy for BKPyV-DNA in the diagnosis of BK polyomavirus-associated nephropathy was evaluated using a receiver operating characteristic (ROC) curve. The coefficients of variation for the repeated detection of BKPyV standard DNA were 2.55 and 4.71 at concentrations of 6.2 and 3.2 log₁₀ IU/mL, respectively. The linear range was 2.2-6.2 log₁₀ IU/mL, and the lowest detection limit was 100 IU/mL. By utilizing histopathological examination of renal biopsy as the gold standard for BKPyV diagnosis, the area under the ROC curve of 74 post-transplantation plasma samples detected by the ddPCR system was found to be 0.875 (95% CI: 0.797-0.953, <i>P</i> < 0.01). The optimal threshold was 512.86 copies/mL, with a sensitivity of 90.0% and a specificity of 67.6%. In comparison, the area under the ROC curve for qPCR was 0.668 (95% CI: 0.583-0.752, <i>P</i> < 0.01), with an optimal threshold of 11,481.54 copies/mL, a sensitivity of 35.0%, and a specificity of 100.0%. Pairwise comparison (Delong test) of the ROC curves of the two systems showed a significant difference in the area under the curve, with a difference of 0.207 and a <i>P</i>-value <0.01. The BKPyV nucleic acid detection system, based on ddPCR, is appropriate for the regular monitoring of the BK polyomavirus, specifically in plasma samples containing low viral DNA loads while it provides the benefits of both absolute quantification and high sensitivity.IMPORTANCEIt was previously believed that droplet digital polymerase chain reaction had limitations, including high cost, limited throughput, and cumbersome operation, which hindered its widespread application in clinical practice. However, the current fully automated digital PCR platform, combined with streamlined operations, can detect 96 samples at once, and the entire process can be completed within an hour, laying a solid foundation for its extensive use.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylacetic acid metabolic genes are associated with <i>Mycobacteroides abscessus</i> dominant circulating clone 1.","authors":"Brittany N Ross, Emma Evans, Marvin Whiteley","doi":"10.1128/spectrum.01330-24","DOIUrl":"10.1128/spectrum.01330-24","url":null,"abstract":"<p><p><i>Mycobacteroides abscessus</i> (MAB) causes lung infections in people with cystic fibrosis (pwCF), and infecting strains show significant genetic variability both between and within individuals. MAB isolates can be divided into dominant clonal clusters (DCCs) or non-clustering groups and can present as smooth or rough colonies on agar plates. Both DCCs and the rough colony morphology have been linked to increased pathogenicity, but the mechanisms are unclear. This study explored the genomes of MAB isolates collected from individuals within the CF@LANTA CF center along with publicly available genomes to identify genes associated with more pathogenic MAB DCCs. Sixty-eight isolates from 26 CF individuals colonized by MAB were morphotyped and sequenced, with almost half of these isolates being members of DCC group 1 (DCC1). While lung function was not significantly impacted by colonization with DCC1 or rough isolates, 102 genes were specifically associated with DCC1 isolates. These genes were enriched for functions in sulfur-based DNA modification, DNA integration, and phenylacetic acid (PAA) catabolism. PAA is produced by the human gut microbiota and found throughout the human body. We show that strains containing PAA metabolic genes allow MAB to use PAA as a sole carbon and energy source. Although the benefits of PAA metabolic genes and other enriched pathways remain unclear, these findings highlight genes associated with emerging MAB CF strains.</p><p><strong>Importance: </strong>A primary challenge in treating bacterial infections is the wide spectrum of disease and genetic variability across bacterial strains. This is particularly evident in <i>Mycobacteroides abscessus</i> (MAB), an emerging pathogen affecting people with cystic fibrosis (pwCF). MAB exhibits significant genetic diversity both within and between individuals. However, seven dominant circulating clones (DCCs) have emerged as the major cause of human infections, demonstrating increased pathogenicity. Understanding the mechanisms underlying this increased pathogenicity and the associated genetic factors is crucial for developing novel treatment strategies. Our findings reveal that specific genes are associated with the DCC1 isolate of MAB, many of which are implicated in antimicrobial susceptibility or virulence.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of a carbohydrate recognition domain-like region in <i>Entamoeba histolytica</i> Gal/GalNAc lectin intermediate subunit.","authors":"Hongze Zhang, Qingshan Li, Hang Zhou, Meng Feng, Yanqing Zhao, Ruixue Zhou, Lijun Chen, Hiroshi Tachibana, Xunjia Cheng","doi":"10.1128/spectrum.00538-24","DOIUrl":"10.1128/spectrum.00538-24","url":null,"abstract":"<p><p><i>Entamoeba histolytica</i> is an enteric protozoan parasite that causes human amebic colitis and extraintestinal abscesses. As a prerequisite for parasite colonization and invasion, adherence of <i>E. histolytica</i> is predominantly mediated by galactose (Gal)- and N-acetyl-d-galactosamine (GalNAc)-inhibitable lectins. The intermediate subunit (Igl) of Gal-/GalNAc-inhibitable lectin is a cysteine-rich protein containing multiple CXXC motifs and is considered a key factor affecting trophozoite's pathogenicity. However, details of the function of Igl during parasite adherence remain unclear. Here, using segmentally expressed Igl proteins and a CHO cell model transfected with Igl fragments, we identified a carbohydrate-recognition domain (CRD)-like region between amino acids 989 and 1,088. Through single- and double-point mutations in the Igl segments, two core CXXC motifs responsible for carbohydrate recognition in the CRD-like region, which are highly conserved among several lectins, were confirmed. In addition to adhesion, the roles of CRD-like region and its core CXXC motifs in various pathogenic effects were further explored. To our knowledge, this is the first report showing an adhesion-related region in <i>E. histolytica</i> Igl. The identification and characterization of this CRD-like region provides further insights into molecular mechanisms underlying <i>E. histolytica</i> pathogenicity and also aids in the determination of a potential drug target in this parasite.</p><p><strong>Importance: </strong><i>Entamoeba histolytica</i> adhesion mainly depends on galactose (Gal)-/N-acetyl-d-galactosamine (GalNAc)-inhibitable lectins, subsequently triggering a series of amebic reactions. Among the three subunits of Gal-/GalNAc-inhibitable lectin, heavy subunit and intermediate subunit (Igl) have exhibited lectin activity, but that of Igl remains poorly understood. In this study, we confirmed a carbohydrate-recognition domain (CRD)-like limiting region in <i>E. histolytica</i> Igl and further identified its two core CXXC motifs responsible for carbohydrate recognition. Moreover, the role of Igl's CRD-like region and its CXXC motifs in hemolysis and pathogenic effects was explored. This is the first study to determine an adhesion-related region in <i>E. histolytica</i> Igl protein, providing a new reference direction for subsequent research studies. Since the potential homogeneity of galectin-2 in several mammals and Igl CRD-like region, it could be meaningful to relate the corresponding pathogeneses and phenotypes of these two proteins. Except for adhesion, studies on the involvement of Igl CRD-like region in different parasite-host interactions are also promising.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the duration of antimicrobial therapy for the treatment of orthopedic hardware infections.","authors":"Rija Asim, Christian J Fuchs, Nathan A Summers","doi":"10.1128/spectrum.01269-24","DOIUrl":"10.1128/spectrum.01269-24","url":null,"abstract":"<p><p>The optimal duration of antimicrobial therapy for orthopedic hardware infections is unclear. We identified 216 patients with orthopedic hardware infections, of whom 42 (19%) later had relapsed infection. Chronic suppressive antimicrobial therapy beyond 12 weeks was not significantly associated with lower odds of relapse.IMPORTANCEThere is debate about how long to continue antibiotics after initial treatment of bone and joint infections when hardware remains in place. This study found no benefit from continuing antibiotics longer than 12 weeks when trying to prevent recurrent infection.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Veillonella parvula</i> acts as a pathobiont promoting the biofilm virulence and cariogenicity of <i>Streptococcus mutans</i> in adult severe caries.","authors":"Yuan Wei, Yu Zhang, Yuan Zhuang, Yifei Tang, Hua Nie, Yequan Haung, Ting Liu, Weidong Yang, Fuhua Yan, Yanan Zhu","doi":"10.1128/spectrum.04318-23","DOIUrl":"10.1128/spectrum.04318-23","url":null,"abstract":"<p><p>Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the <i>S. mutans</i>. Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and <i>gtf</i> (glucosyltransferase) gene expression of <i>S. mutans</i> cocultured with <i>V. parvula</i> which was identified as ASC-related dominant bacterium. The biofilm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the <i>in vivo</i> cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was <i>V. parvula</i>. <i>In vitro</i> experiments found that <i>V. parvula</i> can effectively promote <i>S. mutans</i> mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that <i>V. parvula</i> was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of <i>S. mutans</i> when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that <i>V. parvula</i> may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of <i>S. mutans</i> in the context of ASC.IMPORTANCEAdult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between <i>V. parvula</i> and <i>S. mutans</i> augments the severity of dental caries <i>in vivo</i>, suggesting <i>V. parvula</i> may act as a synergistic pathobiont exacerbating biofilm virulence of <i>S. mutans</i> in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of respiratory pathogens in patients with acute respiratory infections during the COVID-19 pandemic and after easing of COVID-19 restrictions.","authors":"Pei Zhao, Yu Zhang, Jie Wang, Yonghui Li, Yuxin Wang, Yuan Gao, Mengchuan Zhao, Ming Zhao, He Tan, Yanqing Tie, ZhiShan Feng","doi":"10.1128/spectrum.01161-24","DOIUrl":"10.1128/spectrum.01161-24","url":null,"abstract":"<p><p>We aimed to investigate the epidemiological characteristics of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory pathogens among patients with acute respiratory infections (ARIs) in Shijiazhuang, China, during the coronavirus disease 2019 (COVID-19) pandemic (January 2021--December 2022) and after the relaxation of COVID-19 restrictive measures (January 2022--December 2023). This retrospective study enrolled 6,633 ARIs patients who visited the Hebei General Hospital between 2021- and 2023. Nasopharyngeal swabs samples were collected for multiplex PCR detection of 13 common respiratory pathogens. Respiratory pathogens were detected in 31.58% of individuals diagnosed with ARIs, whileereas a co-infection with multiple pathogens was observed in 8.5% of the ARI patients. In the years 2021 and 2022, 326 (27.63%) and 283 (24.38%) respiratory pathogens were found to be positive, respectively, during the COVID-19 pandemic. However, in 2023, subsequent to the easing of COVID-19 restrictions, the positivity rate significantly rose to 34.62%, with 4,292 cases identified. The majority of positive cases over the last three3 years were concentrated in patients under 14 years old. The predominant pathogens identified were human rhinovirus (HRVs) (15.08%) in 2021, mycoplasma pneumonia (MP) (6.46%) in 2022, and influenza A virus (FluA) (11.35%) in 2023. Seasonal prevalence patterns of most pathogens were affected, except for parainfluenza virus (PIV). There was a simultaneous increase in the positive cases and positivity rates of FluA and adenovirus (ADV) Iin 2023, compared to 2021 and 2022. Additionally, the infection rates of respiratory syncytial virus (RSV), MP, and coronavirus (CoV) in 2023 either exceeded or were comparable to those in 2021 and 2022. Conversely, the positivity rates of PIV, RVs, metapneumovirus (MPV), and influenza B virus (FluB) were lower in 2023 compared to 2021 or 2022.</p><p><strong>Importance: </strong>The implementation of strict non-pharmaceutical interventions (NPIs) during the coronavirus disease 2019 (COVID-19) pandemic may lead to changes in the epidemiological features of respiratory pathogens, as well as the occurrence of immune debt, potentially causing a resurgence in respiratory pathogen activity following the easing of strict NPIs measures. There are limited reports on the epidemiological characteristics of respiratory pathogens among patients of all ages with acute respiratory infections (ARIs) during the COVID-19 pandemic and after the easing of COVID-19 restrictions. Our study investigated the epidemiology of 13 respiratory pathogens in Shijiazhuang, China, from January 2021 to December 2023. Thisese data isare crucial for the ongoing surveillance of epidemiological shifts in respiratory pathogens during and post the -COVID-19 pandemic, and serves as a scientific foundation for the prevention and management of ARIs.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates: <i>in vitro</i> and <i>in vivo</i> analyses.","authors":"Chaoqun Zhang, Le Fu, Yuan Zhu, Qigui Chen, Zetong Chen, Yung-Fu Chang, Yide Li, Mengjing Yao, Xinyi Huang, Li Jin, Xue Gao, Yiyu Zhang, Biao Jin, Shuli Chou, Liang Luo","doi":"10.1128/spectrum.00265-24","DOIUrl":"10.1128/spectrum.00265-24","url":null,"abstract":"<p><p>Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine-serine-glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W<b>5</b> demonstrated a rapid and effective sterilization against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W<b>5</b> killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W<b>5</b> also exhibited excellent biocompatibility in both <i>in vitro</i> and <i>in vivo</i> safety evaluations. AMP W<b>5</b> treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections.</p><p><strong>Importance: </strong>Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine-serine-glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}