mSphere最新文献

{"title":"Transformative advances in Guillain-Barré syndrome research.","authors":"Christine M Szymanski, Ashley M Rogers, Leandre M Glendenning, Dee Warmath, Jarrod J Mousa, Tiffany M Daugherty, Nadja Zeltner, Jessica L McAlpine, David R Tribble, Glen A Cook, Geert-Jan Boons, Nowshin Papri, Shoma Hayat, Israt Jahan, Zhahirul Islam, Rachel J Richardson, Charles E Whitehead-Tillery, Julia A Bell, Linda S Mansfield","doi":"10.1128/msphere.00436-26","DOIUrl":"https://doi.org/10.1128/msphere.00436-26","url":null,"abstract":"<p><p>The Guillain-Barré Syndrome Innovation Alliance held its inaugural meeting focused on creating treatment solutions for Guillain-Barré syndrome (GBS), an autoimmune disease increasingly recognized as a postinfectious neuropathy and the most common cause of paralysis since vaccines for polio. These collaborators, funded by the Department of War, Congressionally Directed Medical Research Programs, and the National Institute of Allergy and Infectious Diseases, span institutes/universities, including the University of Georgia, Michigan State University, Florida State University, the University of Utrecht, the International Centre for Diarrhoeal Disease Research, and the Uniformed Services University of the Health Sciences. Group efforts span biochemistry, epidemiology, immunology, medicine, microbiology, microbial ecology, glycobiology, neurology, neuroscience, pharmacology, and multiomics data science/computational biology. Our team is committed to the advancement of two core objectives: expanding understanding of biological mechanisms of GBS and developing more efficacious, targeted therapies. We are dedicated to finding alternative therapies for patients unresponsive to intravenous immunoglobulin and to creating affordable options to eliminate financial barriers to care.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0043626"},"PeriodicalIF":4.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mSphere of Influence: Autoantibodies during malaria-a historical observation taking the modern spotlight.","authors":"Juan Rivera-Correa","doi":"10.1128/msphere.00906-25","DOIUrl":"https://doi.org/10.1128/msphere.00906-25","url":null,"abstract":"<p><p>Juan Rivera-Correa works in the field of immunology of tropical infectious diseases, focusing on the role of autoimmune responses in malaria. In this mSphere of Influence article, he discusses the papers by Rosenberg and Daniel-Ribeiro, which were two of the first papers to report the presence of autoantibodies in malaria patients, changing the paradigm and blurring the line between autoimmune disorders and infectious diseases.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0090625"},"PeriodicalIF":4.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mSphere Legacy: A career built on suppressors.","authors":"Thomas J Silhavy","doi":"10.1128/msphere.00568-26","DOIUrl":"https://doi.org/10.1128/msphere.00568-26","url":null,"abstract":"<p><p>My career in research began in the early 1970s and is now ending. In the early years, I learned much from three wonderful mentors. My research has focused on <i>Escherichia coli</i>, and my studies were motivated by two basic questions: how does this bacterium build its complex cell envelope, and how does it regulate gene expression in response to external stimuli? Much of my success stemmed from searches for suppressors. None of what I write would have been possible without the graduate students and postdocs I have had the pleasure of supervising, and I apologize in advance for not highlighting the contributions of each of you. I have also profited enormously from the contributions of wonderful colleagues and of several valued collaborators, each brought new insights and indispensable expertise.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0056826"},"PeriodicalIF":4.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical isolates of <i>Mycobacterium avium</i> complex reveal an <i>M. intracellulare</i>-associated IL-17/neutrophilic pulmonary immune program in a murine disease model.","authors":"Shintaro Seto, Koji Furuuchi, Shiho Omori, Hajime Nakamura, Kozo Morimoto, Minako Hijikata, Naoto Keicho","doi":"10.1128/msphere.00398-26","DOIUrl":"10.1128/msphere.00398-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Mycobacterium avium&lt;/i&gt; complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises &lt;i&gt;M. avium&lt;/i&gt; (MAV) and &lt;i&gt;M. intracellulare&lt;/i&gt; (MI). Although MAV- and MI-associated pulmonary disease is currently treated using the same guideline-based regimens, whether MAC species and individual isolates elicit distinct pulmonary host responses remains unclear. Here, we established a panel of MAC clinical isolates exhibiting persistent pulmonary infection in mice and performed transcriptomic analyses to evaluate pulmonary immune responses. Although MAC infections induced broadly shared inflammatory responses, MI-infected lungs exhibited a robust IL-17/neutrophilic inflammatory signature, whereas MAV infection showed relative enrichment of IFN-γ-/cytotoxicity-associated responses, indicating differences in the balance of their immune gene expression programs. The MI-associated IL-17/neutrophilic program remained evident at the isolate level and after adjustment for pulmonary colony-forming unit (CFU) values. RT-qPCR and flow cytometric analyses using the representative isolate pair FKJ-1 (MI) and FKJ-8 (MAV) further supported the differential induction of these immune signatures in infected lungs. Single-cell RNA sequencing of lungs infected with FKJ-1 and FKJ-8 demonstrated that infection with the representative MI isolate was associated with increased &lt;i&gt;Il17a&lt;/i&gt;-expressing CD4&lt;sup&gt;+&lt;/sup&gt; T cells and γδ T cells, neutrophilic inflammation, and the expansion of inflammatory macrophages. Together, these findings suggest that, within a selected panel of persistent MAC clinical isolates, MI infection is associated with a robust IL-17/neutrophilic pulmonary immune program. This study provides a preclinical framework for dissecting species- and isolate-associated host-pathogen interactions in MAC-PD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;&lt;i&gt;Mycobacterium avium&lt;/i&gt; complex pulmonary disease (MAC-PD) is an increasing clinical challenge with heterogeneous disease courses and outcomes. Although current guideline-based treatment does not differ between &lt;i&gt;M. avium&lt;/i&gt; (MAV)- and &lt;i&gt;M. intracellulare&lt;/i&gt; (MI)-associated PD, examining whether these species elicit distinct host responses may help explain heterogeneity in disease progression and clinical outcomes and support future patient stratification. We used a panel of MAC clinical isolates that persist or proliferate in mouse lungs to compare host responses induced by MAV and MI. Although both species induced broadly shared inflammation, MI infection was associated with a robust IL-17/neutrophilic program, whereas MAV infection showed relative enrichment of IFN-γ-/cytotoxicity-associated responses. The MI-associated program remained evident at the isolate level and after adjustment for pulmonary colony-forming unit (CFU) values. These findings suggest that MAC species and isolates may shape pulmonary immune landscapes, providing a preclinical framework","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0039826"},"PeriodicalIF":4.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved C-terminal tails link PilC1 and PilC2 to the <i>Kingella kingae</i> type IV pilus through β-strand augmentation with the core minor pilin complex.","authors":"Taylor A Yount, Eric A Porsch, Alexa Mihaita, Aisling Macaraeg, Joseph W St Geme","doi":"10.1128/msphere.00464-26","DOIUrl":"https://doi.org/10.1128/msphere.00464-26","url":null,"abstract":"<p><p><i>Kingella kingae</i> is a gram-negative bacterium that is a leading cause of septic arthritis, osteomyelitis, and a variety of other invasive diseases in young children. Infection begins with colonization of the oropharynx, which depends on type IV pili (T4P), surface appendages that promote adherence, twitching motility, and natural competence. These T4P functions are mediated by two pilus-associated proteins called PilC1 and PilC2, which are members of the PilC/PilY family of proteins. In this study, we used AlphaFold Multimer modeling to identify a conserved C-terminal tail in both PilC1 and PilC2 that is predicted to insert into a hydrophobic pocket in the FimT-PilV-PilW-PilX-PilE core minor pilin complex via β-strand augmentation. Truncation of the final 10 residues of PilC1 or PilC2 significantly impaired pilus biogenesis, adherence to epithelial cells, twitching motility, and natural transformation without altering PilC1 or PilC2 protein expression. Point mutations targeting conserved residues within the PilC2 C-terminal tail had little impact on pilus biogenesis but resulted in a marked reduction in adherence and natural transformation, as well as the elimination of twitching motility. AlphaFold modeling predicted that these conserved residues interact with a β-sheet in the globular domain of the minor pilin PilX. Consistent with this model, site-directed mutagenesis of the PilX β-strand residues predicted to contact PilC2 largely phenocopied the PilC2 C-terminal tail point mutations. Together, these findings establish that the C-terminal tail in PilC/PilY adhesins is a conserved adapter that links these adhesins to T4P through the core minor pilin complex, identifying a potential target for anti-adhesion therapeutic strategies.</p><p><strong>Importance: </strong>Type IV pili (T4P) are dynamic, adhesive surface fibers that are produced by a diverse array of bacteria. A number of T4P systems contain a large pilus-associated protein in the so-called PilC/PilY family that promotes pilus biogenesis and mediates adhesive activity. The pediatric pathogen <i>Kingella kingae</i> produces PilC/PilY family proteins called PilC1 and PilC2, and expression of at least one of these proteins is necessary for the production of functional T4P. Using molecular modeling and mutagenesis approaches, we established that a short peptide at the C-terminal end of these proteins, which is conserved among PilC/PilY family members, is critical for PilC1 and PilC2 functions and mediates these functions via β-strand augmentation with a specific T4P-associated protein complex.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0046426"},"PeriodicalIF":4.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABC and MFS efflux transporters mediate antibiotic resistance and bile salt tolerance in <i>Enterococcus faecalis</i>.","authors":"Q C Truong-Bolduc, Y Wang, S S Mello, M C Phillips, M S Gilmore, D C Hooper","doi":"10.1128/msphere.00489-26","DOIUrl":"https://doi.org/10.1128/msphere.00489-26","url":null,"abstract":"<p><p>Bacteria that reside in the gastrointestinal tract must adapt to the antibacterial properties of bile salts (BSs) and other compounds. We investigated five putative transporters of the enteric-colonizing <i>Enterococcus faecalis</i> for their roles in adaptation to BS and antibiotic resistance. Transcript levels of <i>ef2593</i> and <i>ef0575</i> increased over fivefold, and <i>ef0420</i> increased 12-fold when exposed to 0.02% and 0.1% BS concentrations. No change in the expression of <i>ef2592</i> or e<i>f1814</i> was seen. <i>E. faecalis</i> wild-type MMH594 overexpressing efflux pumps by plasmid constructs (EF2592, EF2593, EF0575, EF0420) or by a pre-exposure to 0.02% BS (EF2593 or EF0420) showed a higher CFU/mL than wild type alone when exposed to 0.3% BS, indicating adaptation of <i>E. faecalis</i> to resist a higher BS level in the medium, and that <i>E. faecalis</i> BS response involved multiple transporters. In MIC assays, the following overexpressors also showed a twofold increase in antibiotic resistance: EF2592 and EF2593 (daptomycin, vancomycin); EF0420 (daptomycin, oritavancin); and EF1814 (daptomycin, levofloxacin, oritavancin, and vancomycin). While no change in EF0575-overexpressor, mutant <i>0575</i> showed a significant increase in susceptibility to daptomycin, linezolid, levofloxacin, and oritavancin. In addition, nisin-induced overexpression of several transporters from a plasmid in <i>Lactococcus lactis</i> also increased the MICs of multiple antibiotics, most notably for EF1814, with a 4- to 16-fold increase in the MICs of daptomycin, levofloxacin, linezolid, and vancomycin. These data indicate that expression of multiple <i>E. faecalis</i> transporters responds to bile salts and may contribute to survival and colonization in the gut, as well as causing low-level multidrug resistance.Bile salts are key antimicrobial components of the gastrointestinal tract, and bacterial adaptation to bile salt stress is critical for host colonization and persistence. In this study, we demonstrate that multiple <i>E. faecalis</i> transporters are induced by bile salts and contribute to adaptation at physiologically relevant bile salt concentrations. Importantly, several of these transporters also confer low-level resistance to clinically important antibiotics, including daptomycin, vancomycin, levofloxacin, linezolid, and oritavancin. These findings suggest that transport systems selected for survival in the intestinal environment may have the unintended consequence of increasing antibiotic tolerance and multidrug resistance. By linking host-associated environmental stress with antimicrobial resistance phenotypes, this work advances our understanding of how gut colonization factors can influence bacterial persistence and therapeutic outcomes. The identified transporters represent potential targets for strategies to limit both intestinal colonization and antibiotic resistance in <i>E. faecalis</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0048926"},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDV-like endogenous viral elements act as immune rheostats in <i>Aedes</i> cells by modulating defensin A-mediated responses to arboviruses.","authors":"Jie Xiao, Tiantian Wei, Hongzheng Lu, Chunyuan Li, Mei Chen, Peiwen Liu, Xiao-Guang Chen, Zetian Lai, Ruiwen Ren, Jinbao Gu","doi":"10.1128/msphere.00520-26","DOIUrl":"10.1128/msphere.00520-26","url":null,"abstract":"<p><p>Mosquito cell lines are essential tools for arbovirus research. Endogenous viral elements (EVEs) are prevalent in mosquito genomes, yet their functional effects on host immune responses remain unclear, potentially complicating experimental interpretations. In this study, we systematically characterized endogenous mosquito densovirus-like elements (EMLs) within the <i>Aedes aegypti</i> Aag2 cell line and found that these endogenous EMLs are transcriptionally active but translationally defective. The silencing of EML transcripts significantly diminished the replication of Zika virus (ZIKV), Japanese encephalitis virus (JEV), and chikungunya virus (CHIKV), while transiently increasing dengue virus 2 (DENV-2), thereby indicating a virus-dependent regulatory mechanism. Mechanistically, RNA sequencing after EML interference, alongside plasmid-based mimic expression, demonstrated that EML transcripts downregulate defensin A, an antimicrobial peptide produced by mosquitoes. Functional assays using synthetic defensin A showed that this peptide differentially regulates arboviral infection. Binding assays and structural modeling further supported its interaction with viral envelope proteins, while stage-restricted infection assays revealed distinct stages of action: defensin A enhanced adsorption of ZIKV, JEV, and CHIKV, but did not promote DENV-2 adsorption or entry, and instead reduced DENV-2 RNA accumulation at the post-entry replication stage. Our findings highlight a previously unrecognized role of densovirus-derived EVEs in mosquito innate immunity, extending their functional scope from the well-established PIWI-interacting RNA-mediated antiviral defense to the regulation of antimicrobial peptide-associated immune pathways. These findings emphasize the necessity of accounting for EVE activity when analyzing data derived from mosquito cell lines, and suggest that related EVE-mediated immune regulation may contribute to arbovirus dynamics in mosquitoes.IMPORTANCEMosquito-borne viruses such as dengue, Zika, Japanese encephalitis, and chikungunya continue to threaten human health worldwide. Laboratory studies often use <i>Aedes aegypti</i> cell lines to investigate how these viruses interact with their mosquito hosts. Here, we show that the genomes of these cells contain endogenous viral elements derived from mosquito densoviruses. Far from being inert fossils, these sequences are transcriptionally active and regulate mosquito immunity by suppressing the antimicrobial peptide defensin A. This immune modulation influences the replication of different arboviruses in opposite ways, enhancing some while restricting others. Our findings reveal that integrated viral elements can shape the outcome of arbovirus infection, with important implications for interpreting mosquito cell culture experiments and for evaluating endogenous viral element-mediated immune regulation in mosquito-virus interactions.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0052026"},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A duty to act.","authors":"Emily Sickbert-Bennett, Philip J Rosenthal, Cesar A Arias, Gonzalo M Bearman, Paul E Sax, Graeme Forrest, David P Calfee, Romney M Humphries, Stanley Maloy, Ravi Jhaveri, Ira Blader, Ashley Shade, Roger Bedimo, Cynthia L Sears, Paul Katz, Barbara Resnick","doi":"10.1128/msphere.00598-26","DOIUrl":"https://doi.org/10.1128/msphere.00598-26","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059826"},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mSphere Legacy: Sharing wisdom at the culmination of a scientific career.","authors":"Ira J Blader","doi":"10.1128/msphere.00376-26","DOIUrl":"10.1128/msphere.00376-26","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0037626"},"PeriodicalIF":4.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448333","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":"Effects of improved water, sanitation, handwashing, and nutrition on early childhood IgG immune repertoire development against <i>Shigella</i> and enteroinvasive <i>Escherichia coli</i> (EIEC).","authors":"Nikolina Walas, Everlyn Kamau, Minlu Zhang, Kathy Kamath, Jack Reifert, John Shon, Shahjahan Ali, Md Ziaur Rahman, Abul K Shoab, Syeda L Famida, Salma Akther, Md Saheen Hossen, Palash Mutsuddi, Mahbubur Rahman, Jessica A Grembi, Andrew N Mertens, Taufiqur R Bhuiyan, Firdausi Qadri, Edward T Ryan, Richelle C Charles, Daniel Leung, Stephen Luby, Audrie Lin, Benjamin F Arnold","doi":"10.1128/msphere.00339-26","DOIUrl":"10.1128/msphere.00339-26","url":null,"abstract":"<p><p>We studied the effects of a combined water, sanitation, handwashing, and nutritional supplementation (WSH + N) intervention on <i>Shigella</i>/EIEC IgG immune development among Bangladeshi children enrolled in a cluster-randomized trial. We used a bacterial display assay to measure IgG-specific binding to <i>Shigella</i>/EIEC Ipa proteins (IpaA, IpaB, IpaC, IpaD, and IpaH) from a substudy of 120 children (60 intervention, 60 control) at median ages 3, 14, and 28 months. We found that the WSH + N intervention did not impact IgG seroprevalence (56% vs 53%, <i>P</i> = 0.6) or IgG epitope repertoire development (<i>P</i> = 0.15-0.97), but there were distinct age-based patterns of IgG linear epitopes and motifs charting the development of the immune repertoire. Samples from before age 6 months, reflecting predominantly maternal IgG, had higher epitope breadth and magnitude compared with samples from older ages. A modeling analysis of maternal-child IgG dynamics suggests that peak susceptibility occurs between 6 and 9 months of age. With this methodology, we found that intensive, household-based WASH interventions were insufficient to impact early childhood immune development to <i>Shigella</i>/EIEC. Our results motivate complementary interventions, such as vaccines, to prevent <i>Shigella</i>/EIEC infection in the first 2 years of life.IMPORTANCE<i>Shigella</i>/EIEC is a leading cause of global diarrheal deaths, especially in low-resource settings. Current interventions against childhood <i>Shigella</i>/EIEC infection focus on reducing exposure, such as through improved water, sanitation, handwashing, and nutritional supplementation (WSH + N). It is unclear how these interventions impact childhood immune development against pathogens. In the present study, we characterize the null impact of a WSH + N intervention on IgG immune responses to <i>Shigella</i>/EIEC in a birth cohort and demonstrate the development of immune responses over the first 2 years of life. We found that maternal IgG wanes between 6 and 9 months, and that peak susceptibility to infection is during this time. From our findings, we provide a modeling framework that can be used to inform vaccination schedules in early childhood after 6 months.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT01590095.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0033926"},"PeriodicalIF":4.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448422","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}