Infection and Immunity最新文献

{"title":"Expression of Concern for Galdiero et al., \"Porins from <i>Salmonella enterica</i> Serovar Typhimurium Activate the Transcription Factors Activating Protein 1 and NF-κB through the Raf-1-Mitogen-Activated Protein Kinase Cascade\".","authors":"","doi":"10.1128/iai.00491-24","DOIUrl":"10.1128/iai.00491-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049124"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750716","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":"Expression of Concern for Galdiero et al., \"Role of Surface-Exposed Loops of <i>Haemophilus influenzae</i> Protein P2 in the Mitogen-Activated Protein Kinase Cascade\".","authors":"","doi":"10.1128/iai.00492-24","DOIUrl":"10.1128/iai.00492-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049224"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750739","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":"The group A <i>Streptococcus</i> pathogenicity island RD2: virulence role and barriers to conjugative transfer.","authors":"Roshika Roshika, Sushila Baral, Ira Jain, Ashna Prabhu, Ameya Singh, Paul Sumby","doi":"10.1128/iai.00273-24","DOIUrl":"10.1128/iai.00273-24","url":null,"abstract":"<p><p>Serotype M28 isolates of the bacterial pathogen the group A <i>Streptococcus</i> (GAS; <i>Streptococcus pyogenes</i>), but not isolates of other serotypes, have a nonrandom association with cases of puerperal sepsis, a life-threatening infection that can occur in women following childbirth. In prior studies, we established that RD2, a pathogenicity island present in all M28 GAS isolates but mostly absent from other serotypes, is a factor in the M28-puerperal sepsis association. Here, we identified a significant reduction in the RD2 conjugation frequency in inter-serotype conjugation assays relative to intra-serotype assays. As isolates of most GAS serotypes produce an antiphagocytic hyaluronic acid capsule, while M28 isolates do not, we tested whether the capsule served as a barrier to RD2 acquisition or maintenance. The data showed that capsule production had no impact on the RD2 conjugation frequency or on the ability of RD2 to enhance vaginal colonization by GAS, but did inhibit the ability of RD2 to enhance GAS adherence to vaginal epithelial cell lines. Further molecular explanations for the inter-serotype barrier to RD2 conjugative transfer were investigated, and a conserved, chromosomally encoded Type I restriction-modification system was identified as being key. We also identified that RD2 modifies the GAS transcriptome, including mRNAs encoding virulence factors with adherence and dissemination roles, following exposure to human plasma. Our data provide insights into factors that contribute to the restriction of the RD2 pathogenicity island to discrete subsets of the GAS population.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0027324"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726809","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":"<i>bb0689</i> contributes to the virulence of <i>Borrelia burgdorferi</i> in a murine model of Lyme disease.","authors":"Connor Waldron, Sierra George, Christina Thompson, Yu Hsien Liao, Zhiming Ouyang","doi":"10.1128/iai.00459-24","DOIUrl":"10.1128/iai.00459-24","url":null,"abstract":"<p><p><i>Borrelia burgdorferi</i>, the Lyme disease pathogen, continuously changes its gene expression profile in order to adapt to ticks and mammalian hosts. The alternative sigma factor RpoS plays a central role in borrelial host adaptation. Global transcriptome analyses suggested that more than 100 genes might be regulated by RpoS, but the main part of the regulon remains unexplored. Here, we showed that the expression of <i>bb0689</i>, a gene encoding an outer surface lipoprotein with unknown function, was activated by RpoS. By analyzing gene expression using luciferase reporter assays and quantitative reverse transcription PCR, we found that expression of <i>bb0689</i> was induced by an elevated temperature, a reduced pH, and increased cell density during <i>in vitro</i> cultivation. The transcriptional start site and a functional promoter for gene expression were identified in the 5' regulatory region of <i>bb0689</i>. The promoter was responsive to environmental stimuli and influenced by RpoS. We also showed that <i>bb0689</i> expression was expressed in <i>B. burgdorferi</i> during animal infection, suggesting the importance of this gene for infection. We further generated a <i>bb0689</i> mutant and found that the infectivity of the mutant was severely attenuated in a murine infection model. Although <i>bb0689</i>-deficient spirochetes exhibited no defect during <i>in vitro</i> growth, they were defective in resistance to osmotic stress. <i>Cis</i>-complementation of the mutant with a wild-type copy of <i>bb0689</i> fully rescued all phenotypes. Collectively, these results demonstrate that the RpoS-regulated gene <i>bb0689</i> is a key contributor to the optimal infection of <i>B. burgdorferi</i> in animals.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0045924"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827790","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":"Polycytotoxic T cells mediate antimicrobial activity against intracellular <i>Mycobacterium tuberculosis</i>.","authors":"Marc Zumwinkel, Aaron Chirambo, Markus Zähnle, Max Bürger, Mark Grieshober, Vincent Romahn, Henry Mwandumba, Steffen Stenger","doi":"10.1128/iai.00297-24","DOIUrl":"10.1128/iai.00297-24","url":null,"abstract":"<p><p>Protection against infections with intracellular bacteria requires the interaction of macrophages and T-lymphocytes, including CD8⁺ T cells. Recently, the expression of natural killer cell receptors NKG2A and NKG2C was introduced as markers of CD8⁺ T-cell subsets. The goal of this study was to functionally characterize human NKG2A and NKG2C-expressing T cells using the major pathogen <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) as a model organism. Sorted NKG2 populations were analyzed for their capacity to proliferate and degranulate and their intracellular expression of cytotoxic molecules. Cytokine release and the effect on bacterial growth were assessed after coculture of NKG2 populations with <i>Mtb</i>-infected macrophages. NKG2A⁺ T cells released higher levels of IFN-γ and IL-10, whereas NKG2C⁺ T cells released higher levels of IL-2, contained the greatest reservoir of intracellular granzyme B and showed a remarkable constitutive level of degranulation. Both subsets inhibited the intracellular growth of <i>Mtb</i> more efficiently than NKG2-negative CD8⁺ T cells. Antimicrobial activity of NKG2⁺ T cells was not associated with the release of cytokines or cytotoxic molecules. However, the frequency of polycytotoxic T cells (P-CTL), defined as CD8⁺ T cells co-expressing granzyme B, perforin, and granulysin, positively correlated with the ability of NKG2-expressing T cells to control <i>Mtb</i>-growth in macrophages. Our results highlight the potential of NKG2-expressing P-CTL to trigger the antibacterial activity of human macrophages. Targeting this population by preventive or therapeutic immune interventions could provide a novel strategy to combat severe infectious diseases such as tuberculosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0029724"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806984","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":"Infection-induced trained immunity: a twist in paradigm of innate host defense and generation of immunological memory.","authors":"Aayush Bahl, Saurabh Pandey, Roopshali Rakshit, Sashi Kant, Deeksha Tripathi","doi":"10.1128/iai.00472-24","DOIUrl":"10.1128/iai.00472-24","url":null,"abstract":"<p><p>In contrast to adaptive immunity, which relies on memory T and B cells for long-term pathogen-specific responses, trained immunity involves the enhancement of innate immune responses through cellular reprogramming. Experimental evidence from animal models and human studies supports the concept of trained immunity and its potential therapeutic applications in the development of personalized medicine. However, there remains a huge gap in understanding the mechanisms, identifying specific microbial triggers responsible for the induction of trained immunity. This underscores the importance of investigating the potential role of trained immunity in redefining host defense and highlights future research directions. This minireview will provide a comprehensive summary of the new paradigm of trained immunity or innate memory pathways. It will shed light on infection-induced pathways through non-specific stimulation within macrophages and natural killer cells, which will be further elaborated in multiple disease perspectives caused by infectious agents such as bacteria, fungi, and viruses. The article further elaborates on the biochemical and cellular basis of trained immunity and its impact on disease status during recurrent exposures. The review concludes with a perspective segment discussing potential therapeutic benefits, limitations, and future challenges in this area of study. The review also sheds light upon potential risks involved in the induction of trained immunity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0047224"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800612","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":"Novel broadly reactive monoclonal antibody protects against <i>Pseudomonas aeruginosa</i> infection.","authors":"Margalida Mateu-Borrás, Spencer R Dublin, Jason Kang, Hunter L Monroe, Emel Sen-Kilic, Sarah J Miller, William T Witt, Joshua A Chapman, Gage M Pyles, Shreeram C Nallar, Annalisa B Huckaby, Evita Yang, Carleena Rocuskie-Marker, Megan E Grund, Md Shahrier Amin, Slawomir Lukomski, Greg A Snyder, Krishanu Ray, George K Lewis, Darrell O Ricke, F Heath Damron, Mariette Barbier","doi":"10.1128/iai.00330-24","DOIUrl":"10.1128/iai.00330-24","url":null,"abstract":"<p><p>The incidence of infections attributed to antimicrobial-resistant (AMR) pathogens has increased exponentially over the recent decades reaching 1.27 million deaths worldwide in 2019. Without intervention, these infections are predicted to cause up to 10 million deaths a year and incur costs of up to 100 trillion US dollars globally by 2050. The emergence of AMR bacteria such as the ESKAPEE pathogens, and in particular <i>Pseudomonas aeruginosa</i> and species from the genus <i>Burkholderia</i>, underscores an urgent need for new therapeutic strategies. Monoclonal antibody (mAb) therapy offers a promising alternative to treat and prevent bacterial infections. In this study, we used peptides from highly conserved areas of the bacterial flagellin to generate monoclonal antibodies capable of broad binding to flagellated Gram-negative bacteria. We generated a broadly reactive IgG2bĸ mAb (WVDC-2109) that recognizes <i>P. aeruginosa, Burkholderia</i> sp., and other Gram-negative pathogens of interest. Characterization of the therapeutic potential of this antibody was determined using <i>P. aeruginosa</i> as model. <i>In vitro</i> characterization of WVDC-2109 demonstrated complement-mediated bactericidal activity and enhanced opsonophagocytosis of <i>P. aeruginosa</i>. Prophylactic administration of WVDC-2109 markedly improved survival and outcome in a lethal sepsis model and a sub-lethal murine pneumonia model of <i>P. aeruginosa</i> infection, reducing bacterial burden and inflammation. These findings suggest that WVDC-2109 and similar FliC-targeting antibodies could be valuable in preventing or treating diseases caused by <i>P. aeruginosa</i> as well as other life-threatening diseases of concern.IMPORTANCEAntimicrobial resistance (AMR) costs hundreds of thousands of lives and billions of dollars annually. To protect the population against these infections, it is imperative to develop new medical countermeasures targeting AMR pathogens like <i>P. aeruginosa</i> and <i>Burkholderia</i> sp. The administration of broadly reactive monoclonal antibodies can represent an alternative to treat and prevent infections caused by multi-drug-resistant bacteria. Unlike vaccines, antibodies can provide protection regardless of the immune status of the infected host. In this study, we generated an antibody capable of recognizing flagellin from <i>P. aeruginosa</i> and <i>B. pseudomallei</i> along with other Gram-negative pathogens of concern. Our findings demonstrate that the administration of the monoclonal antibody WVDC-2109 enhances survival rates and outcomes in different murine models of <i>P. aeruginosa</i> infection. These results carry significant implications in the field given that there are no available vaccines for <i>P. aeruginosa</i>.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033024"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817927","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":"<i>Rickettsia</i> disrupts and reduces endothelial tight junction protein zonula occludens-1 in association with inflammasome activation.","authors":"Loka Reddy Velatooru, Esteban Arroyave, Meagan D Rippee-Brooks, Megan Burch, Ethan Yang, Bing Zhu, David H Walker, Yang Zhang, Rong Fang","doi":"10.1128/iai.00468-24","DOIUrl":"10.1128/iai.00468-24","url":null,"abstract":"<p><p><i>Rickettsia</i> spp. cause life-threatening diseases in humans. The fundamental pathophysiological changes in fatal rickettsial diseases are disrupted endothelial barrier and increased microvascular permeability. However, it remains largely unclear how rickettsiae induce microvascular endothelial injury. In the present study, we demonstrated that <i>Rickettsia conorii</i> infection disrupts the continuous immunofluorescence expression of the interendothelial tight junction protein, zonula occludens-1 (ZO-1), in infected monolayers of microvascular endothelial cells (MVECs), accompanied by significantly diminished total expression levels of ZO-1. Interestingly, <i>R. conorii</i> activated inflammasome in MVECs, as evidenced by cleaved caspase-1 and IL-1β in the cell lysates in association with significantly elevated expression levels of nucleotide binding and oligomerization domain, leucine-rich repeat, and pyrin containing protein 3 (NLRP3). Furthermore, selective inhibition of NLRP3 by MCC950 significantly suppressed the activation and cleavage of caspase-1 induced by <i>R. conorii</i> in endothelial cells, which further prevented the disruption of interendothelial junctions and reduction of ZO-1 expression. Of note, pharmaceutical inhibition of NLRP3 mitigated the disrupted endothelial integrity caused by <i>R. conorii</i>, measured by fluorescein isothiocyanate-dextran passage in a Transwell assay, independent of bacterial growth and cellular cytotoxicity. Taken together, our results suggest that <i>R. conorii</i> affected microvascular endothelial junction integrity likely via diminishing and interrupting the junctional protein ZO-1 in association with activating NLRP3 inflammasome. These data not only highlight the potential of ZO-1 as a biomarker for <i>Rickettsia</i>-induced microvascular injury but also provide insight into targeting NLRP3 inflammasome/ZO-1 signaling as a potentially adjunctive therapeutic approach for severe rickettsioses.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0046824"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827701","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":"Expression of Concern for Galdiero et al., \"<i>Haemophilus influenzae</i> Porin Contributes to Signaling of the Inflammatory Cascade in Rat Brain\".","authors":"","doi":"10.1128/iai.00490-24","DOIUrl":"10.1128/iai.00490-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049024"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750713","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":"The ability of <i>sarA</i> to limit protease production plays a key role in the pathogenesis of <i>Staphylococcus aureus</i> osteomyelitis irrespective of the functional status of <i>agr</i>.","authors":"Karen E Beenken, Mara J Campbell, Mark S Smeltzer","doi":"10.1128/iai.00473-24","DOIUrl":"10.1128/iai.00473-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;We demonstrate that mutation of the staphylococcal accessory regulator A (&lt;i&gt;sarA&lt;/i&gt;) in the USA300 strain LAC limits virulence in a murine osteomyelitis model to a greater extent than mutation of the accessory gene regulator (&lt;i&gt;agr&lt;/i&gt;) and that it does so irrespective of the functional status of &lt;i&gt;agr&lt;/i&gt;. Protease production was decreased in the &lt;i&gt;agr&lt;/i&gt; mutant but increased in &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA/agr&lt;/i&gt; mutants to a degree that limited biofilm formation. Extracellular protein A (eSpa) and full-length extracellular nuclease (Nuc1) were absent in the conditioned medium (CM) from &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA&lt;/i&gt;/&lt;i&gt;agr&lt;/i&gt; mutants, and their abundance was restored in both mutants by eliminating protease production. Cytotoxicity of CM for osteoblasts and osteoclasts was also reduced in both mutants. Cytotoxicity was restored in a protease-deficient &lt;i&gt;sarA&lt;/i&gt; mutant but not in the protease-deficient &lt;i&gt;sarA&lt;/i&gt;/&lt;i&gt;agr&lt;/i&gt; mutant. Reduced cytotoxicity was correlated with the reduced abundance of full-length α-toxin, LukF, and LukS in &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA&lt;/i&gt;/&lt;i&gt;agr&lt;/i&gt; mutants. The abundance of these toxins in their full-length form was increased in the protease-deficient &lt;i&gt;sarA&lt;/i&gt; mutant by comparison to LAC, demonstrating that mutation of &lt;i&gt;sarA&lt;/i&gt; increases the production of these toxins but increased protease production limits their abundance in full-length and presumably functional forms. Most importantly, eliminating protease production enhanced the virulence of &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA/agr&lt;/i&gt; mutants, but had no impact in the &lt;i&gt;agr&lt;/i&gt; mutant. We conclude that a key factor in the attenuation of LAC &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA&lt;/i&gt;/&lt;i&gt;agr&lt;/i&gt; mutants in osteomyelitis is the increased production of extracellular proteases and its impact on virulence factors that contribute to biofilm formation and cytotoxicity.&lt;b&gt;IMPORTANCE&lt;/b&gt;The persistent emergence of antibiotic-resistant strains has rekindled interest in anti-virulence strategies to combat &lt;i&gt;S. aureus&lt;/i&gt; infections. Numerous reports describe anti-virulence strategies focusing on key regulatory elements that globally influence virulence factor production, the two most commonly targeted being the accessory gene regulator (&lt;i&gt;agr&lt;/i&gt;) and the staphylococcal accessory regulator A (&lt;i&gt;sarA&lt;/i&gt;). We demonstrate that mutation of &lt;i&gt;sarA&lt;/i&gt; limits virulence to a greater extent than mutation of &lt;i&gt;agr&lt;/i&gt; and that this can be attributed to increased protease production in both &lt;i&gt;sarA&lt;/i&gt; and &lt;i&gt;sarA&lt;/i&gt;/&lt;i&gt;agr&lt;/i&gt; mutants. This illustrates the critical role of &lt;i&gt;sarA&lt;/i&gt; in protease-mediated post-translational regulation in &lt;i&gt;S. aureus&lt;/i&gt;. It also suggests that an inhibitor of &lt;i&gt;sarA&lt;/i&gt; would be more effective than an inhibitor of &lt;i&gt;agr&lt;/i&gt; in overcoming the therapeutic recalcitrance of osteomyelitis and that such an inhibitor would remain effective even in the context of &lt;i&gt;agr&lt;/i&gt; mutants known to arise &lt;i&gt;in vivo&lt;/i&gt; during the transition from acute to chronic infection","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0047324"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750756","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}