PLoS Pathogens最新文献

{"title":"External factors influence intrinsic differences in Stx2e production by Porcine Shiga Toxin-producing Escherichia coli strains.","authors":"Sander Van Hoorde, Nick Vereecke, Daniel Sperling, Xiaohua He, Emma Vanbeylen, Emma Van Denberghe, Eric Cox, Bert Devriendt","doi":"10.1371/journal.ppat.1013616","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013616","url":null,"abstract":"<p><p>Porcine Shiga toxin-producing Escherichia coli (STEC) strains pose significant challenges to the pig industry. The toxins produced by these strains, particularly Shiga toxin subtype 2e (Stx2e), are associated with a range of clinical symptoms such as diarrhoea and oedema disease, which in severe cases result in death. Understanding the factors that influence the production and secretion of Stx2e is crucial to elucidate porcine STEC pathogenesis and to develop effective therapeutic strategies. Therefore, this study aimed to characterize the variability in Stx2e production among different porcine STEC strains and assess the effect of several external factors, including bile acids and antibiotics. Our results highlighted a substantial variation in extracellular Stx2e levels by porcine STEC strains. In addition, bile acids, especially the bile acid deoxycholate, exerted strain-specific effects on these extracellular Stx2e levels. Antibiotics also affected extracellular Stx2e levels with ciprofloxacin and enrofloxacin inducing a substantial increase in toxin production in certain strains. Genome analysis revealed that these strains encode a holin gene downstream of the Stx2e operon. Deleting this holin gene abolished the antibiotic-induced increase in extracellular Stx2e levels, while introducing holin expression in unresponsive strains increased the presence of Stx2e in the extracellular environment. These findings unravel a role for phage holins in Stx2e secretion and highlight the intricate interplay between genetic and environmental factors in regulating Stx2e production in porcine STEC strains. Together, our results offer insights into STEC pathogenesis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013616"},"PeriodicalIF":4.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"African swine fever virus pB318L suppresses inflammatory response by inhibiting NF-κB activation and NLRP3 inflammasome formation.","authors":"Xiaohong Liu, Guangqiang Ye, Yi Zeng, Hanyu Wu, Siqi Dong, Xiaoping He, Qiongqiong Zhou, Hongyang Liu, Zhaoxia Zhang, Jiangnan Li, Changjiang Weng, Li Huang","doi":"10.1371/journal.ppat.1013558","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013558","url":null,"abstract":"<p><p>African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by African swine fever virus (ASFV), posing significant threats to global swine production. ASFV pathogenesis is closely associated with its sophisticated immune evasion strategies. In this study, we demonstrate that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase (GGPPS) homolog inhibited both the NF-κB signaling pathway and the formation of the NLRP3 inflammasome. Infection with ASFV-intB318L (a recombinant ASFV with pB318L expression inhibition) induced significantly higher levels of IL-1β compared to its parent strain ASFV HLJ/18. Mechanically, pB318L interacts with NEMO to inhibit the interaction between IKKα and NEMO, and suppresses the K63-linked ubiquitination of NEMO mediated by TRIM21. In addition, pB318L interacts with the NACHT and LRR domains of NLRP3, which prevents the oligomerization of NLRP3 by suppressing the interaction between NEK7 and NLRP3. Crucially, the immunosuppressive functions of pB318L on both NF-κB signaling pathway and NLRP3 inflammasome activation are independent of its GGPPS enzymatic activity. In conclusion, we presented evidence that ASFV pB318L negatively regulates NF-κB signaling pathway and NLRP3 inflammasome. This study provides critical mechanistic insights into the role of pB318L in ASFV pathogenesis and highlights its potential as a target for the development of antiviral strategies or live-attenuated vaccines against ASF.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013558"},"PeriodicalIF":4.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection.","authors":"Yunuen Avalos-Padilla, Vasil N Georgiev, Elena Lantero, Silvia Pujals, René Verhoef, Livia N Borgheti-Cardoso, Lorenzo Albertazzi, Rumiana Dimova, Xavier Fernàndez-Busquets","doi":"10.1371/journal.ppat.1013606","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013606","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.ppat.1009455.].</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013606"},"PeriodicalIF":4.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenicity and transmission of Morganella morganii in honey bees.","authors":"Yijun Chen, Qiang Huang","doi":"10.1371/journal.ppat.1013613","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013613","url":null,"abstract":"<p><p>Honey bees provide essential pollination services in the ecosystem. The high annual loss of honey bees has raised concerns about global food security and the agricultural economy. As a primary stressor causing colony failure, the mite Varroa destructor feeds on the hemolymph and the bee's fat body tissue. The Varroa mite-associated deformed wing virus has been extensively studied because it can be found in each individual mite and causes bee mortality. A recent study shows that the Varroa mite can transmit pathogenic bacteria, while the transmission route remains unclear. In this study, we isolated and assembled a previously uncultured bacterium, Morganella morganii, from the mites Varroa destructor. This pathogenic bacterium exhibited a high case fatality rate, as evidenced by 215 cells causing over 30% mortality in pupae and adult bees. Using a fluorescent protein-tagged strain, we provide evidence that M. morganii can not be transmitted among bees through social contacts, while it can be transmitted from mites to bees, and vice versa. The cumulative incidence of transmitting M. morganii from infected bees to mites is 92.1%, and 68.49% from infected mites to naïve bees. Our data aligns with the honey bee colony collapse in winter, when the mite population expands, accelerating the honey bees to tap into a reservoir of this lethal bacterium.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013613"},"PeriodicalIF":4.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of undecaprenyl phosphate recycling suppresses ampC beta-lactamase induction in Pseudomonas aeruginosa.","authors":"Karina Klycheva, Joël Gyger, Mélissa Frund, Gabriel Torrens, Felipe Cava, Coralie Fumeaux","doi":"10.1371/journal.ppat.1013633","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013633","url":null,"abstract":"<p><p>Beta-lactam antibiotics are widely used to treat bacterial infections, but their efficacy is compromised by resistance mechanisms such as the production of beta-lactamases. In Pseudomonas aeruginosa, the chromosomally encoded beta-lactamase AmpC is the primary mediator of beta-lactam resistance. ampC expression is regulated by the transcription factor AmpR, which responds to intracellular peptidoglycan (PG) fragments. Under normal conditions, AmpR binds the PG precursor (UDP-MurNAc-pentapeptide) and represses ampC expression. However, during beta-lactam treatment or in PG recycling-deficient mutants such as ampD mutants, PG degradation products (anhydromuropeptides) accumulate and activate AmpR, resulting in elevated ampC expression and beta-lactam resistance. We hypothesized that shifting the balance of PG precursors could modulate AmpR activity and suppress beta-lactamase expression, even in derepressed strains. Undecaprenyl phosphate (UndP) is a lipid carrier essential for translocating PG precursors across the bacterial inner membrane. Recent work has identified members of the DedA superfamily as UndP flippases responsible for recycling this lipid carrier. Disruption of UndP recycling leads to cytoplasmic accumulation of UDP-MurNAc-pentapeptide, the known AmpR repressor. Here, we show that deletion of dedA4, which encodes a predicted UndP flippase in P. aeruginosa, causes PG precursors accumulation and significantly reduces AmpC production and beta-lactam resistance in an ampD mutant. These findings highlight the influence of PG precursor dynamics on beta-lactamase regulation and identify DedA4 as a promising therapeutic target. Inhibiting UndP recycling offers a novel strategy to counteract beta-lactam resistance in P. aeruginosa and potentially other AmpC-producing pathogens.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013633"},"PeriodicalIF":4.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Starve or share? Phosphate availability shapes plant-microbe interactions.","authors":"Maja Schmidt, Kiran Raj, Judith Salas-Oropeza, Oswaldo Valdés-López, Martina K Ried-Lasi","doi":"10.1371/journal.ppat.1013601","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013601","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013601"},"PeriodicalIF":4.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of HIV-1-specific antibody-mediated effector functions by native-like envelope trimers in humans.","authors":"Marloes Grobben, Emma I M M Reiss, Angela I Schriek, Karlijn van der Straten, Nathalie Dereuddre-Bosquet, Pauline Maisonnasse, Alex Rooker, Chunhao Yu, Khadija Tejjani, Monica Tolazzi, Kwinten Sliepen, Réka Felfödiné Lévai, Attila Farsang, Roger Le Grand, Gabriella Scarlatti, Robin J Shattock, Steven W de Taeye, Godelieve J de Bree, Rogier W Sanders, Marit J van Gils","doi":"10.1371/journal.ppat.1013614","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013614","url":null,"abstract":"<p><p>A protective vaccine is urgently needed to curb the ongoing global HIV-1 epidemic. There is increased interest to develop a vaccine able to induce both neutralizing antibodies and antibody-mediated effector functions for additional efficacy. We investigated the ability of a group M consensus envelope glycoprotein (Env) trimer vaccine ConM SOSIP.v7 to induce antibodies that mediate effector functions in preclinical and clinical studies. We found that the ConM SOSIP.v7 protein immunogen in combination with MPLA adjuvant induced diverse antibody-mediated effector functions in human volunteers participating in a phase 1 trial. Moreover, the functional antibody response was higher in female compared to male participants. The same immunogen induced similar antibody-mediated effector functions in preclinical studies using rabbits and non-human primates. In these preclinical models, we demonstrated that alterations in the vaccine regimen, including immunization route and adjuvant, could modulate vaccine immunogenicity and lead to functionally different antibody responses. Specifically, we observed that intramuscular immunization led to more functional antibody responses compared to subcutaneous vaccine administration, and that the MPLA liposomes and squalene emulsion adjuvants induced functionally different antibody responses. In conclusion, this study shows that HIV-1 native-like Env trimers are able to elicit antibody-mediated effector functions in humans and that preclinical studies had predictive value. Furthermore, the preclinical studies revealed that different vaccine formulations and administration routes yield qualitatively different antibody-mediated effector functions. Our findings should guide interpretation of preclinical HIV-1 vaccine studies and can inform the design of HIV-1 vaccine regimens aimed at inducing antibody-mediated effector functions in addition to neutralization capacity.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013614"},"PeriodicalIF":4.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.","authors":"Anna K Großkopf, Victor Tobiasson, Laurie T Krug","doi":"10.1371/journal.ppat.1013263","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013263","url":null,"abstract":"<p><p>Interactions between viral glycoproteins and cellular receptors determine virus tropism and represent promising targets for vaccines. Eph receptor tyrosine kinases are conserved receptors for the human oncogenic gammaherpesviruses, Kaposi sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), and mediate entry into target cells by interaction with the viral gH/gL glycoprotein complex. To evaluate the use of murine gammaherpesvirus 68 (MHV68), a natural pathogen of rodents, as an in vivo model system for early events in gammaherpesvirus infection, we characterized the interaction of the MHV68 gH/gL complex with Eph receptors. We demonstrate a direct interaction of MHV68 gH/gL with EphA4 and EphB3, that is conserved between human and murine receptors. Pre-incubation of MHV68 inocula with soluble decoy receptors decreased infection of permissive fibroblasts. Ectopic expression of EphA4 and EphB3 enabled MHV68 to infect otherwise non-permissive human B cells, demonstrating EphA4 and EphB3 receptor function. Targeted mutations informed by protein structure predictions demonstrate that the MHV68 gH/gL-Eph interaction is determined by domain I (D-I) and follows structural motifs previously described in the KSHV gH/gL-EphA2 complex. The importance of gH D-I is further highlighted by the analysis of gH-targeting neutralizing antibodies. Antibody adsorption via the full gH ectodomain or gH D-I led to comparable reductions in neutralization capacity of serum from WT infected mice, indicating the Eph-binding domain is a major target for gH/gL-directed neutralizing antibodies. Our study characterizes Eph receptors as novel interaction partners and entry receptors for MHV68. Conservation of entry mechanisms provides the basis for future in vivo analyses of the contribution of Eph receptors to cell-type dependent MHV68 infection, as well as targeted strategies to prevent transmission and diseases associated with chronic infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013263"},"PeriodicalIF":4.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human monoclonal antibodies to HPV16 show evidence for common developmental pathways and public epitopes.","authors":"Joseph J Carter, Nicholas K Hurlburt, Erin M Scherer, Suruchi Singh, Justas V Rodarte, Robin A Smith, Peter Lewis, Rachel Kinzelman, Jacqueline Kieltyka, Madelyn E Cabã, Gregory C Wipf, Marie Pancera, Denise A Galloway","doi":"10.1371/journal.ppat.1013086","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013086","url":null,"abstract":"<p><p>Antibodies to human papillomavirus (HPV) primarily recognize surface exposed residues on five loops of the major capsid protein (L1) that vary significantly among HPV types. We determined which loops were required for neutralization for 68 HPV16 specific human monoclonal antibodies (mAbs) cloned from participants who received an HPV vaccine and describe molecular features of those antibodies. Chimeric HPV16 pseudovirus (cpsV), each having one surface loop bearing multiple amino acid substitutions, were used to determine neutralization specificity. The HPV16-FG-loop was the loop most frequently required for neutralization (42 of 68, 61.8%), however, all surface loops were required for neutralization by multiple mAbs: HI (13, 19.1%), DE (15, 22.1%), EF (five, 7.4%), BC (four, 5.9%). Antibodies that required multiple loops were common (17, 25.0%). Three mAbs (4.4%) required sequences on the c-terminus of L1 and for another three mAbs the neutralization specificity could not be determined. Two types of mAbs appeared to be overrepresented: ten mAbs used immunoglobin heavy chain variable region 2-70 (IGHV2-70) with immunoglobin light chain variable region 1-40 (IGLV1-40), having characteristic mutations in complementarity determining region two (CDRL2) of the light chain. Cryogenic electron microscopy (Cryo-EM) revealed that two of these antibodies bound five Fabs per capsomer interacting with all five L1-surface loops. The other type of mAbs that appeared to be overrepresented were nine mAbs using IGHV4-34, six of which also used DH3-16*02 with conserved CDRH3 sequences. Cryo-EM for one of these mAbs, that required the FG-loop for neutralization, was shown to bind one Fab per capsomer at the apex, interacting with the DE- and FG-loops, with sequences of the Fab CDRH3 inserted between the DE- and FG-loops from two L1 proteins. These two types of mAbs were found in the four participants suggesting that these antibodies shared developmental pathways and bound to similar immunodominant epitopes on the virus.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013086"},"PeriodicalIF":4.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.","authors":"Xiao Peng, Cheng-Der Liu, Bidisha Mitra, Elena S Kim, Ning Sun, Andrea Jurado, Hu Zhang, Shitao Li, Tongqing Zhou, Haitao Guo","doi":"10.1371/journal.ppat.1013581","DOIUrl":"10.1371/journal.ppat.1013581","url":null,"abstract":"<p><p>The circulating hepatitis B virus (HBV) e antigen (HBeAg) is known to subvert the host immune system to benefit chronic HBV infection. However, the biological function of a major intracellular form of HBeAg, specifically the precore protein intermediate of 22 kDa (p22) lacking the N-terminal signal peptide, remains largely unclear. Through pull-down and mass spectrometry analysis, we re-identified the complement C1q binding protein (C1QBP) as a p22-binding protein. Immunofluorescence results demonstrated that C1QBP was predominantly localized in the mitochondrial matrix and the leaked C1QBP interacted with p22 in the cytosol. Using co-immunoprecipitation assay, we mapped the arginine-rich, highly positively charged C-terminal domain (CTD) of p22 and the internal domain aa 74-160 of C1QBP as binding domains for p22-C1QBP interaction. By studying the impact of C1QBP on HBV replication, we found that C1QBP overexpression led to the autolysosomal degradation of HBV core protein (HBc) and significantly reduced viral nucleocapsid formation in a p22-dependent manner. Additionally, a C1QBP mutant without the mitochondrial targeting signal (MTS) exhibited a greater inhibitory effect on HBV replication compared to the wild type (wt). Although HBc and p22 share the same CTD sequence, C1QBP does not bind to wt HBV capsid. However, disrupting capsid assembly by HBc-Y132A mutant or CAM-A (class A capsid assembly modulator) treatment enables HBc-C1QBP interaction. Moreover, C1QBP binds to the CTD of HBc on the cytoplasmic deproteinated relaxed circular DNA (DP-rcDNA)-containing capsid that is partially disassembled, hindering DP-rcDNA nuclear import and subsequent covalently closed circular DNA (cccDNA) formation. Collectively, our study suggests that C1QBP inhibits HBV replication through dual mechanisms, proposing a novel therapeutic approach for managing chronic HBV infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 10","pages":"e1013581"},"PeriodicalIF":4.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}