Infection and Immunity最新文献

{"title":"Evidence for a model of conformational change by the <i>Plasmodium falciparum</i> circumsporozoite protein during sporozoite development in the mosquito host through the use of camelid single-domain antibodies.","authors":"Rob Geens, Line De Vocht, Manuela C Aguirre-Botero, Cécile Vincke, Ema Romão, Stefan Magez, Serge Muyldermans, Rogerio Amino, Yann G-J Sterckx","doi":"10.1128/iai.00081-25","DOIUrl":"https://doi.org/10.1128/iai.00081-25","url":null,"abstract":"<p><p><i>Plasmodium</i> sporozoites (SPZs) are formed in the <i>Anopheles</i> mosquito midgut from where they travel to the salivary glands and subsequently to the mammalian liver after deposition into the skin. The SPZ's main surface antigen, the circumsporozoite protein (CSP), plays a pivotal role in SPZ biology and constitutes the immunodominant target for host antibodies. In this study, we raised single-domain antibodies (sdAbs) against CSP from <i>P. falciparum</i> (PfCSP) by immunizing two alpacas with recombinant versions of the antigen. We found that all identified sdAbs specifically target PfCSP's globular [Formula: see text]TSR domain without cross-reacting with <i>P. berghei</i> CSP. Further characterization revealed that most sdAbs recognize native PfCSP on the SPZ surface, although they do not have any inhibitory effect on hepatocyte binding and invasion. Structural studies showed that all binders target the previously identified [Formula: see text]-epitope, confirming the non-protective nature of this epitope. Comparison of sdAb binding to midgut and salivary gland SPZs revealed a shift in the exposure and accessibility of the [Formula: see text]-epitope. Hence, our findings provide further evidence that CSP undergoes structural changes during SPZ development in the mosquito host.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0008125"},"PeriodicalIF":2.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and preclinical efficacy characterization of ShecVax, a combined vaccine against <i>Shigella</i> and enterotoxigenic <i>Escherichia coli</i>.","authors":"Siqi Li, Ipshita Upadhyay, Hyesuk Seo, Sai S R Vakamalla, Aashwina Madhwal, David A Sack, Weiping Zhang","doi":"10.1128/iai.00004-25","DOIUrl":"https://doi.org/10.1128/iai.00004-25","url":null,"abstract":"<p><p>No licensed vaccines are available for the largely antibiotic-resistant <i>Shigella</i> or enterotoxigenic <i>Escherichia coli</i> (ETEC), the two most common bacteria causing children's diarrhea and travelers' diarrhea. Virulence heterogeneity is a key obstacle to developing vaccines against <i>Shigella</i> or ETEC. By applying a multiepitope fusion antigen (MEFA) vaccinology platform, we recently constructed epitope- and structure-based polyvalent proteins to induce cross-protective antibodies against heterogeneous <i>Shigella</i> or ETEC strains. In this study, we combined a polyvalent <i>Shigella</i> protein with two polyvalent ETEC proteins, examined antigen compatibility and broad immunogenicity, and evaluated the potential of developing a combined vaccine against the two groups of bacteria. Data showed that mice intramuscularly immunized with the combined vaccine candidate (ShecVax) developed antibodies to all the following target virulence factors: <i>Shigella</i> IpaB, IpaD, VirG, GuaB, StxA, Stx2A, and StxB, and ETEC STa, LT, CFA/I, CS1, CS2, CS3, CS4, CS5, and CS6. ShecVax-induced antibodies significantly inhibited the invasion of all <i>Shigella</i> species and important serotypes, prevented the adherence of all important ETEC pathotypes, and neutralized the enterotoxicity of ETEC toxins STa and LT. Moreover, ShecVax prevented mice from lethal pulmonary infection with <i>Shigella sonnei</i> or <i>S. flexneri</i> 2a, significantly reduced ETEC bacterial colonization in rabbit small intestines, and passively protected newborn pigs against ETEC toxin-mediated clinical diarrhea. These results indicated that ShecVax is broadly immunogenic and cross-protective against <i>Shigella</i> and ETEC, suggesting ShecVax can be a <i>Shigella</i>/ETEC combined vaccine against children's and travelers' diarrhea, and the MEFA platform can be generally applied for vaccine development against heterogeneous pathogens or different diseases.IMPORTANCEThere are no effective countermeasures against <i>Shigella</i> and enterotoxigenic <i>E. coli</i> (ETEC), two antibiotic-resistant groups of bacteria and the leading causes of diarrhea in children in developing countries (children's diarrhea) and international travelers (travelers' diarrhea). Vaccines are a more practical approach to protect against infectious diseases, including diarrhea caused by <i>Shigella</i> or ETEC. A combined vaccine cross-protective against <i>Shigella</i> and ETEC can save hundreds of thousands of lives and prevent hundreds of millions of diarrhea cases yearly; it can also reduce antibiotic prescription and decrease antibiotic resistance, thus significantly improving global health. In addition, we may apply the MEFA platform to develop combined vaccines against heterogeneous pathogens or different diseases to accommodate an increasingly crowded expanded program on immunization (EPI).</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0000425"},"PeriodicalIF":2.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterologous prime-boost immunization of two-component vaccine candidate PWDVax protected pigs against F18 enterotoxigenic <i>Escherichia coli</i> post-weaning diarrhea.","authors":"Chongyang Zhang, Siqi Li, Ipshita Upadhyay, Sai Simah Reddy Vakamalla, Kathyrn L Lauder, Chance Hansen, Kristen Ann Massey, Courtney Hayes, Nicole L Herndon, Weiping Zhang","doi":"10.1128/iai.00406-24","DOIUrl":"10.1128/iai.00406-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Post-weaning diarrhea (PWD) is associated predominantly with enterotoxigenic &lt;i&gt;Escherichia coli&lt;/i&gt; (ETEC) and continuously causes significant economic losses to swine producers worldwide. Currently, there are no effective countermeasures against this significant swine disease. Challenges persist in developing vaccines against PWD since ETEC strains produce heterogeneous virulence factors, including F4 (K88) and F18 fimbria and heat-labile toxin (LT), heat-stable toxin type I (STa), heat-stable toxin II (STb), and Shiga toxin type 2e (Stx2e, also causes edema disease). An effective PWD vaccine would induce broadly protective immunity, ideally against two fimbriae and four toxins. In this study, by applying a novel epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform, we created a monomeric polyvalent fimbria-toxin protein (fimbria-toxin MEFA) and a holotoxin-structured protein to target PWD virulence determinants (F4 and F18 fimbriae and LT, STa, STb, and Stx2e toxins) and developed a two-component multivalent PWD vaccine candidate, PWDVax. We further applied a heterologous prime-boost immunization strategy and assessed vaccine protection against F18 ETEC-associated PWD. Piglets, after being primed intramuscularly with a fimbria-toxin MEFA monomer protein and boosted orally with live &lt;i&gt;Escherichia coli&lt;/i&gt; bacteria producing GM&lt;sub&gt;1&lt;/sub&gt;-binding holotoxin-structured fimbria-toxin MEFA, developed IgG and secretory IgA responses to the target fimbriae and toxins. Challenged with an F18ac ETEC strain, the immunized piglets were protected against watery diarrhea (87.5%) or any diarrhea (66.7%). These data indicated that PWDVax protects against F18 ETEC-associated PWD and can become an effective PWD vaccine. The two-component vaccine and heterologous prime-boost immunization strategy may be instructive for developing neonatal vaccines in general.IMPORTANCEEnterotoxigenic &lt;i&gt;Escherichia coli&lt;/i&gt; (ETEC)-associated post-weaning diarrhea (PWD) is a global swine disease, remains a major threat to pig health and well-being, and causes significant economic losses. Currently, there are no effective vaccines available against this disease because of challenges including heterogeneity among ETEC strains (or virulence factors) and difficulties in inducing protective immunity against some key virulence determinants. PWDVax, a two-component PWD vaccine candidate, unprecedentedly targeted two ETEC fimbriae (F4 and F18) and four toxins (LT, STa, STb, and Stx2e), the virulence factors associated with nearly all PWD clinical cases. Under a heterologous prime-boost immunization schedule, it induced broad systemic and mucosal antigen-specific antibodies but also protected weaned piglets against F18 ETEC diarrhea. This makes PWDVax potentially an effective vaccine to protect against PWD, particularly the current F18 ETEC-associated severe PWD outbreaks in the United States. Additionally, the two-component vaccine and heterologous","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0040624"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604757","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":"Type I IFNs contribute to upregulation of PD-L1 during <i>Chlamydia trachomatis</i> infection.","authors":"Nicole V Reinhold-Larsson, Michael N Starnbach","doi":"10.1128/iai.00040-25","DOIUrl":"10.1128/iai.00040-25","url":null,"abstract":"<p><p><i>Chlamydia trachomatis</i> is an obligate intracellular bacterial pathogen that if left untreated can cause reproductive harm. Failure of natural adaptive immunity results in chronic and repeat infections. In efforts to understand the failure of adaptive immunity, we have previously discovered that CD8⁺ T cells, normally integral for controlling intracellular pathogen infections, are misprogrammed by PD-1/PD-L1 signaling during <i>in vivo C. trachomatis</i> infection and fail to mount a protective response. Seeking to uncover the pathways and host factors involved in PD-L1 upregulation that may lead to CD8⁺ T-cell inhibition, we discovered that <i>C. trachomatis</i> triggers the secretion of host type I interferons (IFNs) that are necessary and sufficient to upregulate PD-L1 <i>in vitro</i>. Additionally, secretion of type I IFNs is dependent on <i>C. trachomatis</i> development and its type III secretion system. We have also validated that type I IFNs contribute to upregulation of PD-L1 during <i>C. trachomatis</i> infection <i>in vivo</i> using a mouse model of infection. Overall, these findings reveal that <i>C. trachomatis</i> induction of this host pathway may contribute to adaptive immune evasion.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0004025"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604762","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 call for healing and unity.","authors":"Patrick D Schloss","doi":"10.1128/iai.00098-25","DOIUrl":"10.1128/iai.00098-25","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0009825"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515499","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":"Extracellular adherence proteins reduce matrix porosity and enhance <i>Staphylococcus aureus</i> biofilm survival during prosthetic joint infection.","authors":"Mohini Bhattacharya, Tyler D Scherr, Jessica Lister, Tammy Kielian, Alexander R Horswill","doi":"10.1128/iai.00086-25","DOIUrl":"10.1128/iai.00086-25","url":null,"abstract":"<p><p>Biofilms are a cause of chronic, non-healing infections. <i>Staphylococcus aureus</i> is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of <i>S. aureus</i> biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap proteins <i>in vivo</i> using a mouse model of <i>S. aureus</i> prosthetic joint infection. The Results suggest that the protection conferred to biofilms by Eap proteins is a function of biofilm structural stability that interferes with the leukocyte response to biofilm-associated bacteria.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0008625"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673773","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 call for the United States to continue investing in science.","authors":"Ira Blader, Felicia Goodrum, Michael J Imperiale, Arturo Casadevall, Cesar A Arias, Andreas Baumler, Carey-Ann D Burnham, Christina A Cuomo, Corrella S Detweiler, Graeme N Forrest, Jack A Gilbert, Susan Lovett, Stanley Maloy, Alexander McAdam, Irene Newton, Gemma Reguera, George A O'Toole, Patrick D Schloss, Ashley Shade, Marvin Whiteley","doi":"10.1128/iai.00100-25","DOIUrl":"10.1128/iai.00100-25","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0010025"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515504","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>Borrelia miyamotoi in vivo</i> antigenic variation demonstrated by serotype reisolations from infected mice.","authors":"Brittany A Armstrong, Kevin S Brandt, Robert D Gilmore","doi":"10.1128/iai.00484-24","DOIUrl":"10.1128/iai.00484-24","url":null,"abstract":"<p><p>Relapsing fever <i>Borrelia</i> (RFB) employs antigenic variation to alter its surface protein structure in response to host immune pressure. This process occurs by the single translocation of archived variable major protein (Vmp) pseudogenes into a <i>vmp</i> expression locus. <i>Borrelia miyamotoi</i>, phylogenetically grouped with RFB, has the genetic makeup for antigenic variation, but it has not been determined whether <i>B. miyamotoi</i> can create new variant serotypes <i>in vivo</i>. We inoculated mice with a non-clonal parental <i>B. miyamotoi</i> CT13-2396 strain with a known Vmp majority serotype with spirochete isolation at various days post-infection. The <i>vmp</i> that determined the reisolated variant serotype was identified by PCR of the expression locus followed by DNA sequencing of the amplified product. For each mouse reisolate, new variants replaced the parent majority serotype. Moreover, some mice produced additional variant reisolates days apart, indicative of the presentation seen in relapsing fever infections. Infection of mice with a clonal population resulted in the elimination of the inoculated serotype and isolation of new variants. Mouse serum obtained following infection revealed IgM antibodies reactive to the parent Vmp serotype, suggesting that the immune response eliminated or greatly reduced the majority population. These results demonstrated that <i>B. miyamotoi</i> reisolated from infected mice exhibited serotype populations differing from the inoculated strain, indicating the spirochetes underwent antigenic variation to evade the host's immune response. However, whether the observed variation occurred by way of outgrowth of minority populations or by translocation of archived pseudogenes to the expression locus creating new variants awaits further study.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0048424"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572838","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 a <i>Coxiella burnetii</i> outer membrane porin required for intracellular replication.","authors":"Zi Yang, Jeffrey K Duncan-Lowey, Craig R Roy","doi":"10.1128/iai.00448-24","DOIUrl":"10.1128/iai.00448-24","url":null,"abstract":"<p><p><i>Coxiella burnetii</i> is a gram-negative, obligate intracellular pathogen that causes human Q fever. Within host cells, <i>C. burnetii</i> proliferates in a spacious, acidic, lysosome-derived <i>Coxiella</i>-containing vacuole (CCV) by a process that requires the Dot/Icm type IVB secretion system to deliver effectors that manipulate host cell functions. A previous transposon mutagenesis screen identified the gene <i>cbu0937</i> as being important for intracellular replication of <i>C. burnetii</i>. Here, the function of Cbu0937 was investigated. The <i>cbu0937</i>::Tn mutant had no detectable defect replicating in the axenic acidified citrate cysteine medium 2. Additionally, intracellular replication of the <i>cbu0937</i>::Tn mutant was not restored by co-infection of host cells with an isogenic wild-type strain of <i>C. burnetii</i>. Thus, the <i>cbu0937</i>::Tn mutant has a cell-intrinsic intracellular replication defect. Intracellular replication of the <i>cbu0937</i>::Tn mutant was restored by complementing the gene <i>in trans</i> with a plasmid encoding either untagged or an epitope-tagged version of Cbu0937. Analysis of the predicted structure of the Cbu0937 protein using AlphaFold revealed high similarity between Cbu0937 and several bacterial porins. Fractionation studies and surface labeling of <i>C. burnetii</i> producing a functional epitope-tagged protein indicated the localization of Cbu0937 to the bacterial outer membrane. From these data, we conclude that <i>cbu0937</i> encodes a porin that plays an essential role in supporting <i>C. burnetii</i> intracellular replication, which likely involves the acquisition of an important metabolite in the CCV lumen.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0044824"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604759","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>Entamoeba gingivalis</i> induces gingival cell death, collagen breakdown, and host immune response via VAMP8/-3-driven exocytosis pathways.","authors":"Lea Rosenfeld, Nico Neumann, Xin Bao, Aysegül Adam, Arne S Schaefer","doi":"10.1128/iai.00005-25","DOIUrl":"10.1128/iai.00005-25","url":null,"abstract":"<p><p>The protozoan <i>Entamoeba gingivalis</i> commonly colonizes anaerobic periodontal pockets, induces a severe innate immune response, invades gingival mucosa, and kills epithelial cells. <i>E. gingivalis</i> infection is associated with the common oral inflammatory disease periodontitis. DNA variants in vesicle-associated membrane proteins (VAMP) -3 and -8 genes are linked to increased periodontitis risk. These genes mediate host-pathogen interactions, including mucin exocytosis to form protective barriers and matrix metalloproteinase (MMP) secretion in intestinal amoebiasis caused by <i>Entamoeba histolytica</i>. This study aimed to investigate the roles of VAMP3/8 in gingival defense and <i>E. gingivalis</i> infection mechanisms. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing was used to create VAMP3/8-deficient gingival epithelial cells and fibroblasts. Functional analyses included immunofluorescence, enzyme-linked immunosorbent assay (ELISA), cytotoxicity, and collagenase assays. VAMP8 co-localized with mucins in gingival epithelial cells (gECs), and VAMP3 with MMPs in gingival fibroblasts. In gECs<i>, E. gingivalis</i> infection increased mucin (MUC1: 3.6×, MUC21: 14.4×) and interleukin secretion (IL-8, IL-1B: >6×, <i>P</i> = 0.019). <i>VAMP8</i> deficiency in gECs caused higher cell death (35% vs 4% in controls) with reduced exocytosis of mucins and interleukins. Likewise, <i>E. gingivalis</i>-induced VAMP8 translocation into lipid rafts was lost in VAMP8 knockout cells, validating the participation of VAMP8 in exocytosis. In wild-type but not VAMP3-deficient gingival fibroblasts, <i>E. gingivalis</i> strongly activated collagenases. <i>E. gingivalis</i> effects were more pathogenic than those of the oral anaerobic bacterium <i>Porphyromonas gingivalis. E. gingivalis</i> exploits VAMP8/3-driven exocytosis pathways, driving inflammation and tissue destruction, underscoring its role as a significant periodontal pathogen.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0000525"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673769","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}