Infection and Immunity最新文献

{"title":"Glucose uptake is essential for <i>Brucella abortus</i> growth in the extracellular space of the murine placenta.","authors":"Leticia Lázaro-Antón, Thaynara Parente de Carvalho, Eric Pirillo, Mariana X Byndloss, Vladimir E Diaz-Ochoa, Briana M Young, Renato de Lima Santos, Renée M Tsolis","doi":"10.1128/iai.00060-25","DOIUrl":"10.1128/iai.00060-25","url":null,"abstract":"<p><p><i>Brucella abortus</i> infects the placenta of its natural bovine host, which results in abortion and transmission of infection to other cattle and to humans. While the metabolism of <i>B. abortus</i> during chronic infection of the mononuclear phagocyte system has been studied, the nutrients fueling growth of <i>B. abortus</i> in the placenta are unknown. We found that in mice, glucose is an important carbon source for <i>B. abortus</i> in the placenta. A <i>gluP</i> mutant lacking a major facilitator superfamily protein required for glucose uptake had diminished growth in the placenta of pregnant mice and caused reduced inflammatory pathology and fetal demise. The <i>gluP</i> mutant was able to replicate intracellularly in a trophoblast cellular model and to cause trophoblast cell death in infected placentas. Attenuated growth of the <i>gluP</i> mutant was maintained in mice conditionally deficient for peroxisome proliferator-activated receptor γ in macrophages, suggesting that M2-like macrophages were not the major site for glucose-dependent growth of <i>B. abortus</i> in the placenta. Our results show that the infected placenta contains multiple distinct nutrient niches and that glucose utilization within the interstitial space of the placenta is an important process contributing to bacterial growth and fetal demise during placental <i>B. abortus</i> infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0006025"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604756","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":"Structural basis of aggregative adherence fimbriae II interactions with sialic acid, mucin, and human intestinal cells.","authors":"Luke W Hagin, Inácio Mandomando, Fernando Ruiz-Perez, Nathan T Wright, Laura A Gonyar","doi":"10.1128/iai.00483-24","DOIUrl":"10.1128/iai.00483-24","url":null,"abstract":"<p><p>Enteroaggregative <i>Escherichia coli</i> (EAEC) is a common cause of diarrhea worldwide and is associated with growth faltering in developing countries. EAEC are defined by a characteristic adherence pattern mediated by the aggregative adherence fimbriae (AAFs). Despite the critical role of AAF in the definition of the EAEC pathotype, it is not known what host molecules mediate adherence and EAEC pathogenesis during infection of the human gastrointestinal tract. Multiple receptor candidates have been proposed based on <i>in vitro</i> experimentation. We propose that AAFs interact with multiple receptors during colonization of the human gastrointestinal mucosa, and we hypothesize that structural features of the AafA protein (the major subunit of AAF variant II produced by EAEC strain 042) promote these diverse interactions. In this study, we utilize a panel of AafA variants encoding single amino acid substitutions to understand the role of individual residues in biofilm formation as well as adherence to mucin, fibronectin, and human intestinal cells. We identify both charged and uncharged residues that participate in these interactions, and these residues cluster in two regions of the protein that may define a binding pocket at the junction of polymerized subunits. Although both bovine submaxillary mucin and human fibronectin are sialylated molecules, adherence to mucin is diminished by the removal of sialic acid residues while adherence to fibronectin is not, suggesting that the mechanisms of adherence to these molecules are distinct. Overall, our data provide insight into the structural features that determine AAF/II binding to mucin, sialic acid, and human intestinal cells.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0048324"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541796","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":"Identification of glyoxalase A in group B <i>Streptococcus</i> and its contribution to methylglyoxal tolerance and virulence.","authors":"Madeline S Akbari, Luke R Joyce, Brady L Spencer, Amanda Brady, Kevin S McIver, Kelly S Doran","doi":"10.1128/iai.00540-24","DOIUrl":"10.1128/iai.00540-24","url":null,"abstract":"<p><p>Group B <i>Streptococcus</i> (GBS) is a Gram-positive pathobiont that commonly colonizes the gastrointestinal and lower female genital tracts but can cause sepsis and pneumonia in newborns and is a leading cause of neonatal meningitis. Despite the resulting disease severity, the pathogenesis of GBS is not completely understood, especially during the early phases of infection. To investigate GBS factors necessary for bloodstream survival, we performed a transposon (Tn) mutant screen in our bacteremia infection model using a GBS <i>mariner</i> transposon mutant library previously developed by our group. We identified significantly underrepresented mutations in 623 genes that contribute to survival in the blood, including those encoding known virulence factors such as capsule, the β-hemolysin, and inorganic metal ion transport systems. Most of the underrepresented genes have not been previously characterized or studied in GBS, including <i>gloA</i> and <i>gloB,</i> which are homologs for genes involved in methylglyoxal (MG) detoxification. MG is a byproduct of glycolysis and a highly reactive toxic aldehyde that is elevated in immune cells during infection. Here, we observed MG sensitivity across multiple GBS isolates and confirmed that <i>gloA</i> contributes to MG tolerance and invasive GBS infection. We show specifically that <i>gloA</i> contributes to GBS survival in the presence of neutrophils and depleting neutrophils in mice abrogates the decreased survival and infection of the <i>gloA</i> mutant. The requirement of the glyoxalase pathway during GBS infection suggests that MG detoxification is important for bacterial survival during host-pathogen interactions.IMPORTANCEA transposon-mutant screen of group B <i>Streptococcus</i> (GBS) in a bacteremia mouse model of infection revealed virulence factors known to be important for GBS survival such as the capsule, β-hemolysin/cytolysin, and genes involved in metal homeostasis. Many uncharacterized factors were also identified including genes that are part of the metabolic pathway that breaks down methylglyoxal (MG). The glyoxalase pathway is the most ubiquitous metabolic pathway for MG breakdown and is only a two-step process using glyoxalase A (<i>gloA</i>) and B (<i>gloB</i>) enzymes. MG is a highly reactive byproduct of glycolysis and is made by most cells. Here, we show that in GBS, the first enzyme in the glyoxalase pathway, encoded by <i>gloA</i>, contributes to MG resistance and blood survival. We further demonstrate that GloA contributes to GBS survival against neutrophils <i>in vitro</i> and <i>in vivo</i> and, therefore, is an important virulence factor required for invasive infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0054024"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500794","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 hypervirulent Type-1/Type-17 phenotype of <i>Cryptococcus neoformans</i> clinical isolates is specific to A/J mice.","authors":"Minna Ding, Katrina M Jackson, Madeline Harris-Gordon, Thamotharampillai Dileepan, David B Meya, Kirsten Nielsen","doi":"10.1128/iai.00585-24","DOIUrl":"10.1128/iai.00585-24","url":null,"abstract":"<p><p><i>Cryptococcus neoformans</i> is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Both host- and pathogen-specific factors are known to affect patient outcome, and recent studies showed that strain-specific differences in <i>C. neoformans</i> clinical isolates can influence virulence in A/J mice. However, it is unclear how the immunologic and genetic background of inbred mouse strains affects disease outcome during <i>C. neoformans</i> infection. In this study, we show that a hypervirulent phenotype is dependent on the host immune response and mouse genetic background. A/J mice intranasally infected with the hypervirulent isolates, UgCl247, UgCl422, and UgCl236, have increased neutrophil and T-cell recruitment when compared with infection with the reference strain KN99α. In addition, the cytokine profile of the hypervirulent isolates in A/J mice had a profound IFNγ and IL-17 response, and lung resident CD4 T-cells isolated from A/J mice expressed significantly increased Th1 (CXCR3, Tbet) and Th17 (RORγT) markers compared with KN99α infection. Intriguingly, when C57BL/6J mice were infected with these isolates, the hypervirulent phenotype was not evident, and all isolates had virulence comparable to the KN99α control. The immune response in C57BL/6J mice was also nearly identical in response to infections with the hypervirulent isolates and the KN99α control strain. Finally, we determined that the hypervirulent phenotype in A/J mice is not caused by known genetic mutations in the A/J inbred mouse background. Overall, this study demonstrates that an inbred mouse inhalation model can be used to identify host- and pathogen-specific factors that affect <i>C. neoformans</i> disease progression.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0058524"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541798","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":"Sphingosine-mediated death of <i>Pseudomonas aeruginosa</i> involves degradation of cardiolipin by the maintenance of outer lipid asymmetry system.","authors":"Heike Grassmé, Gregory C Wilson, Yuqing Wu, Mike Hasenberg, Simone Keitsch, Federico Caicci, Michael J Edwards, Ildiko Szabo, Erich Gulbins","doi":"10.1128/iai.00591-24","DOIUrl":"10.1128/iai.00591-24","url":null,"abstract":"<p><p>Respiratory infections with multiresistant <i>Pseudomonas aeruginosa</i> are a major clinical problem, affecting mainly patients with pre-existing lung diseases such as cystic fibrosis (CF) or chronic obstructive pulmonary disease but also immunocompromised or elderly patients. We have previously shown that sphingosine, which is abundantly present on epithelial cells of the respiratory tract in healthy humans and wild-type mice, but almost undetectable on the surface of epithelial cells of the respiratory tract from CF patients and CF mice, efficiently kills many bacterial species <i>in vitro</i> and <i>in vivo</i>. Here, we show that sphingosine very rapidly induces marked changes in the membrane of <i>P. aeruginosa</i> with a rolling of the membrane followed by destruction of the bacteria. Sphingosine induced a degradation of cardiolipin via the maintenance of lipid asymmetry (Mla) system in <i>P. aeruginosa</i>. Degradation of cardiolipin induced by sphingosine is prevented in <i>P. aeruginosa</i> mutants of MlaY and reduced in mutants of MlaZ and MlaA. Mutants of MlaY and MlaZ were resistant to sphingosine-induced death of <i>P. aeruginosa</i>. In summary, our data indicate that sphingosine induces the death of <i>P. aeruginosa</i> by a persisting degradation of cardiolipin by the Mla system leading to severe membrane changes in bacteria, while leaving mammalian cells, devoid of cardiolipin in their plasma membrane, alive.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0059124"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585599","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":"Global changes in <i>Staphylococcus aureus</i> virulence and metabolism during colonization of healthy skin.","authors":"Timothy J Enroth, Morgan M Severn, Flavia G Costa, Alyson R Bovee, Reid V Wilkening, Dustin T Nguyen, Christophe Langouët-Astrié, Alexander R Horswill","doi":"10.1128/iai.00028-25","DOIUrl":"10.1128/iai.00028-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> and its antibiotic-resistant derivative, methicillin-resistant <i>S. aureus</i> (MRSA), are the leading causative agents of skin and soft tissue infections globally. <i>S. aureus</i> transiently colonizes the skin of healthy adults, and this transient colonization likely precedes an active infection. In recent years, there have been efforts to elucidate specific factors that help MRSA transition to an active infection, but the specific genetic determinants required for this transition following skin colonization are largely unknown. To address this question, we developed a model of asymptomatic colonization of mouse skin by MRSA. From this model, we could determine the MRSA and mouse transcriptional profiles by RNA sequencing (RNAseq) at 5- and 24-hour post-colonization. The <i>fadXDEBA</i> locus, required for fatty acid metabolism, was highly upregulated in our data, as were numerous virulence factors. RNAseq data were confirmed via functional <i>in vitro</i> and <i>in vivo</i> promoter-fusion assays using live bioluminescent imaging of the <i>fadXDEBA</i> locus promoter driving <i>fadB</i> transcription. We analyzed the functional capacity of members of the <i>fadXDEBA</i> locus, which encode crucial enzymatic components of the <i>S. aureus</i> β-oxidation pathway. The genes <i>fadD</i> and <i>fadA</i> modulate MRSA resistance to fosfomycin and other oxidative stressors during growth in the presence of the common skin fatty acid, palmitic acid. Overall, our data demonstrate that there are global changes to the MRSA transcriptome, priming the bacteria for survival by upregulation of known virulence factors and metabolic genes implicated in host skin-nutrient utilization.IMPORTANCE<i>Staphylococcus aureus</i> is a major global agent of skin and soft tissue infections. <i>S. aureus</i> colonizes the skin transiently, an important precursor to infection. However, little is known about how <i>S. aureus</i> adapts to the skin at the transcriptional level. This study provides an overview of the <i>S. aureus</i> transcriptome during mouse skin colonization via RNA sequencing. We identified that the most highly upregulated genes during colonization are related to fatty acid metabolism. The disruption of certain genes in the fatty acid degradation pathway altered resistance of <i>S. aureus</i> to the antibiotic fosfomycin. This study provides an important step in understanding the transcriptional changes that occur during <i>S. aureus</i> skin colonization and may reveal novel targets of therapeutic interest for preventing skin infections.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0002825"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673776","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":"Polyphosphatases have a polyphosphate-independent influence on the virulence of <i>Cryptococcus neoformans</i>.","authors":"Kabir Bhalla, Eddy Sánchez León-Hing, Yu-Hsuan Huang, Victoria French, Guanggan Hu, Jen Wang, Matthias Kretschmer, Xianya Qu, Raphaell Moreira, E Johan Foster, Pauline Johnson, James W Kronstad","doi":"10.1128/iai.00072-25","DOIUrl":"10.1128/iai.00072-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Cryptococcus neoformans,&lt;/i&gt; an invasive basidiomycete fungal pathogen, causes one of the most prevalent, life-threatening diseases in immunocompromised individuals and accounts for ~19% of AIDS-associated deaths. Therefore, understanding the pathogenesis of &lt;i&gt;C. neoformans&lt;/i&gt; and its interactions with the host immune system is critical for developing therapeutics against cryptococcosis. Previous studies demonstrated that &lt;i&gt;C. neoformans&lt;/i&gt; cells lacking polyphosphate (polyP), an immunomodulatory polyanionic storage molecule, display altered cell surface architecture but unimpaired virulence in a murine model of cryptococcosis. However, the relevance of cell surface changes and the role of hyperaccumulation of polyP in the virulence of &lt;i&gt;C. neoformans&lt;/i&gt; remain unclear. Here we show that mutants with abundant polyP due to loss of the polyphosphatases Xpp1 and Epp1 are attenuated for virulence. The double mutant differed from the wild type during disease by demonstrating a higher fungal burden in disseminated organs at the experimental endpoint and by provoking an altered immune response. An analysis of triple mutants lacking the polyphosphatases and the Vtc4 protein for polyP synthesis also caused attenuated virulence in mice, thus suggesting an influence of Xpp1 and/or Epp1 independent of polyP levels. A more detailed characterization revealed that Xpp1 and Epp1 play multiple roles by contributing to the organization of the cell surface, virulence factor production, the response to stress, and mitochondrial function. Overall, we conclude that polyphosphatases have additional functions in the pathobiology of &lt;i&gt;C. neoformans&lt;/i&gt; beyond an influence on polyP levels.IMPORTANCECryptococcus neoformans causes one of the most prevalent fungal diseases in people with compromised immune systems and accounts for ~19% of AIDS-associated deaths worldwide. The continual increase in the incidence of fungal infections and limited treatment options necessitate the development of new antifungal drugs and improved diagnostics. Polyphosphate (polyP), an under-explored biopolymer, functions as a storage molecule, modulates the host immune response, and contributes to the ability of some fungal and bacterial pathogens to cause disease. However, the role of polyP in cryptococcal disease remains unclear. In this study, we report that the polyphosphatase enzymes that regulate polyP synthesis and turnover contribute to the virulence of &lt;i&gt;C. neoformans&lt;/i&gt; in a mouse model of cryptococcosis. The polyphosphatases influenced the survival of &lt;i&gt;C. neoformans&lt;/i&gt; in macrophages and altered the host immune response. In addition, the mutants lacking the enzymes have changes in cell surface architecture and size, as well as defects in both mitochondrial function and the stress response. By using mutants defective in the polyphosphatases and polyP synthesis, we demonstrate that many of the phenotypic contributions of the polyphosphatases are independent of polyP.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0007225"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604760","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>Helicobacter pylori</i> CagA and Cag type IV secretion system activity have key roles in triggering gastric transcriptional and proteomic alterations.","authors":"Jennifer H B Shuman, Aung Soe Lin, Mandy D Westland, Kaeli N Bryant, Gabrielle E Fortier, M Blanca Piazuelo, Michelle L Reyzer, Audra M Judd, Tina Tsui, W Hayes McDonald, Mark S McClain, Kevin L Schey, Holly M Algood, Timothy L Cover","doi":"10.1128/iai.00595-24","DOIUrl":"10.1128/iai.00595-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Colonization of the human stomach with &lt;i&gt;cag&lt;/i&gt; pathogenicity island (PAI)-positive &lt;i&gt;Helicobacter pylori&lt;/i&gt; strains is associated with increased gastric cancer risk compared to colonization with &lt;i&gt;cag&lt;/i&gt; PAI-negative strains. To evaluate the contributions of the Cag type IV secretion system (T4SS) and CagA (a secreted bacterial oncoprotein) to gastric molecular alterations relevant for carcinogenesis, we infected Mongolian gerbils with a Cag T4SS-positive wild-type (WT) &lt;i&gt;H. pylori&lt;/i&gt; strain, one of two Cag T4SS mutant strains (∆&lt;i&gt;cagT&lt;/i&gt; or ∆&lt;i&gt;cagY&lt;/i&gt;), or a ∆&lt;i&gt;cagA&lt;/i&gt; mutant for 12 weeks. Histologic staining revealed a biphasic distribution of gastric inflammation severity in WT-infected animals and minimal inflammation in animals infected with mutant strains. Atrophic gastritis (a premalignant condition), dysplasia, and gastric adenocarcinoma were only detected in WT-infected animals with high inflammation scores. Transcriptional profiling, liquid chromatography-tandem mass spectrometry analysis of micro-extracted tryptic peptides, and imaging mass spectrometry revealed more than a thousand molecular alterations in gastric tissues from WT-infected animals with high inflammation scores compared to uninfected tissues and few alterations in tissues from other groups of infected animals. Proteins with altered abundance in animals with severe Cag T4SS-induced inflammation mapped to multiple pathways, including the complement/coagulation cascade and proteasome pathway. Proteins exhibiting markedly increased abundance in tissues from &lt;i&gt;H. pylori&lt;/i&gt;-infected animals with severe inflammation included calprotectin components, proteins involved in proteasome activation, polymeric immunoglobulin receptor (PIGR), interferon-inducible guanylate-binding protein (GBP2), lactoferrin, lysozyme, superoxide dismutase, and eosinophil peroxidase. These results demonstrate key roles for CagA and Cag T4SS activity in promoting gastric mucosal inflammation, transcriptional alterations, and proteomic alterations relevant to gastric carcinogenesis.&lt;b&gt;IMPORTANCE&lt;/b&gt;&lt;i&gt;Helicobacter pylori&lt;/i&gt; colonizes the stomachs of about half of humans worldwide, and its presence is the primary risk factor for the development of stomach cancer. &lt;i&gt;H. pylori&lt;/i&gt; strains isolated from humans can be broadly classified into two groups based on whether they contain a chromosomal &lt;i&gt;cag&lt;/i&gt; pathogenicity island, which encodes a secreted effector protein (CagA) and components of a type IV secretion system (T4SS). In experiments using a Mongolian gerbil model, we found that severe gastric inflammation and gastric transcriptional and proteomic alterations related to gastric cancer development were detected only in animals infected with a wild-type &lt;i&gt;H. pylori&lt;/i&gt; strain containing CagA and an intact Cag T4SS&lt;i&gt;.&lt;/i&gt; Mutant strains lacking CagA or Cag T4SS activity successfully colonized the stomach without inducing detectable pathologic host responses. These findings ill","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0059524"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566962","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>Peromyscus leucopus</i>, <i>Mus musculus</i>, and humans have distinct transcriptomic responses to larval <i>Ixodes scapularis</i> bites.","authors":"Jeffrey S Bourgeois, Julie E McCarthy, Siu-Ping Turk, Stephanie S You, Quentin Bernard, Luke H Clendenen, Gary P Wormser, Luis A Marcos, Kenneth Dardick, Sam R Telford, Adriana R Marques, Linden T Hu","doi":"10.1128/iai.00065-25","DOIUrl":"10.1128/iai.00065-25","url":null,"abstract":"<p><p><i>Ixodes scapularis</i> ticks are an important vector for at least seven tick-borne human pathogens, including a North American Lyme disease spirochete, <i>Borrelia burgdorferi</i>. The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval <i>I. scapularis</i> and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural <i>I. scapularis</i> host <i>Peromyscus leucopus</i>, a non-natural rodent host, <i>Mus musculus</i> (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in <i>P. leucopus</i> compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite sites. We also note that bite sites on BALB/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval <i>I. scapularis</i> and <i>P. leucopus</i> and, in addition, expand our overall understanding of <i>I. scapularis</i> feeding.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0006525"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604755","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":"A CRISPRi library screen in group B <i>Streptococcus</i> identifies surface immunogenic protein (Sip) as a mediator of multiple host interactions.","authors":"K Firestone, K P Gopalakrishna, L M Rogers, A Peters, J A Gaddy, C M Nichols, M H Hall, H N Varela, S M Carlin, G H Hillebrand, E J Giacobe, D M Aronoff, T A Hooven","doi":"10.1128/iai.00573-24","DOIUrl":"10.1128/iai.00573-24","url":null,"abstract":"<p><p>Group B <i>Streptococcus</i> (GBS; <i>Streptococcus agalactiae</i>) is an important pathobiont capable of colonizing various host environments, contributing to severe perinatal infections. Surface proteins play critical roles in GBS-host interactions; however, comprehensive studies of these proteins' functions have been limited by genetic manipulation challenges. This study leveraged a CRISPR interference (CRISPRi) library to target genes encoding surface-trafficked proteins in GBS, identifying their roles in modulating macrophage cytokine responses. Bioinformatic analysis of 654 GBS genomes revealed 66 conserved surface protein genes. Using a GBS strain expressing chromosomally integrated dCas9, we generated and validated CRISPRi strains targeting these genes. THP-1 macrophage-like cells were exposed to ethanol-killed GBS variants, and pro-inflammatory cytokines TNF-⍺ and IL-1β were measured. Notably, knockdown of the <i>sip</i> gene, encoding the Surface Immunogenic Protein (Sip), significantly increased IL-1β secretion, implicating Sip in caspase-1-dependent regulation. Furthermore, Δ<i>sip</i> mutants demonstrated impaired biofilm formation, reduced adherence to human fetal membranes, and diminished uterine persistence in a mouse colonization model. These findings suggest that Sip modulates GBS-host interactions critical for pathogenesis, underscoring its potential as a therapeutic target or vaccine component.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0057324"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673771","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}