PLoS Pathogens最新文献

{"title":"The 2 faces of plant SUMOylation against viruses.","authors":"Blanca Sabarit, Eduardo R Bejarano","doi":"10.1371/journal.ppat.1012701","DOIUrl":"10.1371/journal.ppat.1012701","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012701"},"PeriodicalIF":5.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848012","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":"Activation of the tick Toll pathway to control infection of Ixodes ricinus by the apicomplexan parasite Babesia microti.","authors":"Marie Jalovecka, Laurence Malandrin, Veronika Urbanova, Sazzad Mahmood, Pavla Snebergerova, Miriama Peklanska, Veronika Pavlasova, Radek Sima, Petr Kopacek, Jan Perner, Ondrej Hajdusek","doi":"10.1371/journal.ppat.1012743","DOIUrl":"10.1371/journal.ppat.1012743","url":null,"abstract":"<p><p>The vector competence of blood-feeding arthropods is influenced by the interaction between pathogens and the immune system of the vector. The Toll and IMD (immune deficiency) signaling pathways play a key role in the regulation of innate immunity in both the Drosophila model and blood-feeding insects. However, in ticks (chelicerates), immune determination for pathogen acquisition and transmission has not yet been fully explored. Here, we have mapped homologs of insect Toll and IMD pathways in the European tick Ixodes ricinus, an important vector of human and animal diseases. We show that most genes of the Toll pathway are well conserved, whereas the IMD pathway has been greatly reduced. We therefore investigated the functions of the individual components of the tick Toll pathway and found that, unlike in Drosophila, it was specifically activated by Gram-negative bacteria. The activation of pathway induced the expression of defensin (defIR), the first identified downstream effector gene of the tick Toll pathway. Borrelia, an atypical bacterium and causative agent of Lyme borreliosis, bypassed Toll-mediated recognition in I. ricinus and also resisted systemic effector molecules when the Toll pathway was activated by silencing its repressor cactus via RNA interference. Babesia, an apicomplexan parasite, also avoided Toll-mediated recognition. Strikingly, unlike Borrelia, the number of Babesia parasites reaching the salivary glands during tick infection was significantly reduced by knocking down cactus. The simultaneous silencing of cactus and dorsal resulted in greater infections and underscored the importance of tick immunity in regulating parasite infections in these important disease vectors.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012743"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840141","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":"Climate change and Vibrio vulnificus dynamics: A blueprint for infectious diseases.","authors":"Jane M Jayakumar, Jaime Martinez-Urtaza, Kyle D Brumfield, Antarpreet S Jutla, Rita R Colwell, Otto X Cordero, Salvador Almagro-Moreno","doi":"10.1371/journal.ppat.1012767","DOIUrl":"10.1371/journal.ppat.1012767","url":null,"abstract":"<p><p>Climate change is having increasingly profound effects on human health, notably those associated with the occurrence, distribution, and transmission of infectious diseases. The number of disparate ecological parameters and pathogens affected by climate change are vast and expansive. Disentangling the complex relationship between these variables is critical for the development of effective countermeasures against its effects. The pathogen Vibrio vulnificus, a naturally occurring aquatic bacterium that causes fulminant septicemia, represents a quintessential climate-sensitive organism. In this review, we use V. vulnificus as a model organism to elucidate the intricate network of interactions between climatic factors and pathogens, with the objective of identifying common patterns by which climate change is affecting their disease burden. Recent findings indicate that in regions native to V. vulnificus or related pathogens, climate-driven natural disasters are the chief contributors to their disease outbreaks. Concurrently, climate change is increasing the environmental suitability of areas non-endemic to their diseases, promoting a surge in their natural populations and transmission dynamics, thus elevating the risk of new outbreaks. We highlight potential risk factors and climatic drivers aggravating the threat of V. vulnificus transmission under both scenarios and propose potential measures for mitigating its impact. By defining the mechanisms by which climate change influences V. vulnificus disease burden, we aim to shed light on the transmission dynamics of related disease-causing agents, thereby laying the groundwork for early warning systems and broadly applicable control measures.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012767"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840145","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":"Sniffer restricts arboviral brain infections by regulating ROS levels and protecting blood-brain barrier integrity in Drosophila and mosquitoes.","authors":"Rui Hu, Mengzhu Li, Shulin Chen, Man Wang, Xinjun Tao, Yihan Zhu, Huan Yan, Yuan Liu","doi":"10.1371/journal.ppat.1012797","DOIUrl":"10.1371/journal.ppat.1012797","url":null,"abstract":"<p><p>Arthropod-borne viruses (arboviruses) are transmitted to humans by arthropod vectors and pose a serious threat to global public health. Neurotropic arboviruses including Sindbis virus (SINV) persistently infect the central nervous system (CNS) of vector insects without causing notable pathological changes or affecting their behavior or lifespan. However, the mechanisms by which vector insects evade these viral infections in the brains are poorly understood. In this study, we found that loss of the carbonyl reductase Sniffer (Sni) led to a significant increase in SINV infection in the Drosophila brain. Sni regulates reactive oxygen species (ROS) levels, and its depletion leads to elevated ROS, which in turn disrupts the septate junctions (SJs) between subperineurial glia (SPG) cells, compromising the integrity and barrier function of the blood-brain barrier (BBB). Genetic and pharmacological reduction of ROS restored BBB integrity and reduced viral load in the brains of Sni-depleted flies. Additionally, we identified Sni homologs and revealed that the antiviral function of Sni is highly conserved in mosquitoes, where it regulates ROS and protects BBB integrity. Our results revealed an evolutionarily conserved antiviral mechanism in which Sni acts as an antioxidant that protects BBB integrity and restricts viral infection in the vector insect brain.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012797"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840156","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":"Deep phosphoproteomics of Klebsiella pneumoniae reveals HipA-mediated tolerance to ciprofloxacin.","authors":"Payal Nashier, Isabell Samp, Marvin Adler, Fiona Ebner, Lisa Thai Lê, Marc Göppel, Carsten Jers, Ivan Mijakovic, Sandra Schwarz, Boris Macek","doi":"10.1371/journal.ppat.1012759","DOIUrl":"10.1371/journal.ppat.1012759","url":null,"abstract":"<p><p>Klebsiella pneumoniae belongs to the group of bacterial pathogens causing the majority of antibiotic-resistant nosocomial infections worldwide; however, the molecular mechanisms underlying post-translational regulation of its physiology are poorly understood. Here we perform a comprehensive analysis of Klebsiella phosphoproteome, focusing on HipA, a Ser/Thr kinase involved in antibiotic tolerance in Escherichia coli. We show that overproduced K. pneumoniae HipA (HipAkp) is toxic to both E. coli and K. pneumoniae and its toxicity can be rescued by overproduction of the antitoxin HipBkp. Importantly, HipAkp overproduction leads to increased tolerance against ciprofloxacin, a commonly used antibiotic in the treatment of K. pneumoniae infections. Proteome and phosphoproteome analyses in the absence and presence of ciprofloxacin confirm that HipAkp has Ser/Thr kinase activity, auto-phosphorylates at S150, and shares multiple substrates with HipAec, thereby providing a valuable resource to clarify the molecular basis of tolerance and the role of Ser/Thr phosphorylation in this human pathogen.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012759"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818861","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":"Structure of the Pseudomonas aeruginosa PAO1 Type IV pilus.","authors":"Hannah Ochner, Jan Böhning, Zhexin Wang, Abul K Tarafder, Ido Caspy, Tanmay A M Bharat","doi":"10.1371/journal.ppat.1012773","DOIUrl":"10.1371/journal.ppat.1012773","url":null,"abstract":"<p><p>Type IV pili (T4Ps) are abundant in many bacterial and archaeal species, where they play important roles in both surface sensing and twitching motility, with implications for adhesion, biofilm formation and pathogenicity. While Type IV pilus (T4P) structures from other organisms have been previously solved, a high-resolution structure of the native, fully assembled T4P of Pseudomonas aeruginosa, a major human pathogen, would be valuable in a drug discovery context. Here, we report a 3.2 Å-resolution structure of the P. aeruginosa PAO1 T4P determined by electron cryomicroscopy (cryo-EM). PilA subunits constituting the T4P exhibit a classical pilin fold featuring an extended N-terminal α-helix linked to a C-terminal globular β-sheet-containing domain, which are packed tightly along the pilus, in line with models derived from previous cryo-EM data of the P. aeruginosa PAK strain. The N-terminal helices constitute the pilus core where they stabilise the tubular assembly via hydrophobic interactions. The α-helical core of the pilus is surrounded by the C-terminal globular domain of PilA that coats the outer surface of the pilus, mediating interactions with the surrounding environment. Comparison of the P. aeruginosa PAO1 T4P with T4P structures from other organisms, both at the level of the pilin subunits and the fully assembled pili, confirms previously described common architectural principles whilst highlighting key differences between members of this abundant class of prokaryotic filaments. This study provides a structural framework for understanding the molecular and cell biology of these important cellular appendages mediating interaction of prokaryotes to surfaces.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012773"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819403","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":"SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis.","authors":"Areej A Alfaifi, Tristan W Wang, Paola Perez, Ahmed S Sultan, Timothy F Meiller, Peter Rock, David E Kleiner, Daniel S Chertow, Stephen M Hewitt, Billel Gasmi, Sydney Stein, Sabrina Ramelli, Daniel Martin, Blake M Warner, Mary Ann Jabra-Rizk","doi":"10.1371/journal.ppat.1012375","DOIUrl":"10.1371/journal.ppat.1012375","url":null,"abstract":"<p><p>Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation. In this study, we performed studies to investigate the implications of SARS-CoV-2 infection on salivary histatin-5 production and Candida colonization. Bulk RNA-sequencing of parotid salivary glands from COVID-19 autopsies demonstrated statistically significant decreased expression of histatin and amylase genes. In situ hybridization, coupled with immunofluorescence for co-localization of SARS-CoV-2 spike and histatin in salivary gland cells, showed that histatin was absent or minimally present in acinar cells with replicating viruses. To investigate the clinical implications of these findings, salivary histatin-5 levels and oral Candida burden in saliva samples from three independent cohorts of mild and severe COVID-19 patients and matched healthy controls were evaluated. Results revealed significantly reduced histatin-5 in SARS-CoV-2 infected subjects, concomitant with enhanced prevalence of C. albicans. Analysis of prospectively recovered samples indicated that the decrease in histatin-5 is likely reversible in mild-moderate disease as concentrations tended to increase during the post-acute phase. Importantly, salivary cytokine profiling demonstrated correlations between activation of the Th17 inflammatory pathway, changes in histatin-5 concentrations, and subsequent clearance of C. albicans in a heavily colonized subject. The importance of salivary histatin-5 in controlling the proliferation of C. albicans was demonstrated using an ex vivo assay where C. albicans was able to proliferate in COVID-19 saliva with low histatin-5, but not with high histatin-5. Taken together, the findings from this study potentially implicate SARS-CoV-2 infection of salivary glands with compromised oral innate immunity, and potential predisposition to oral candidiasis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012375"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819328","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":"Seasonal influenza a virus lineages exhibit divergent abilities to antagonize interferon induction and signaling.","authors":"Joel Rivera-Cardona, Neeha Kakuturu, Elizabeth F Rowland, Qi Wen Teo, Elizabeth A Thayer, Timothy J C Tan, Jiayi Sun, Collin Kieffer, Nicholas C Wu, Christopher B Brooke","doi":"10.1371/journal.ppat.1012727","DOIUrl":"10.1371/journal.ppat.1012727","url":null,"abstract":"<p><p>The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells is responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection. We developed a flow cytometry-based method to examine transcriptional changes in IFN and interferon stimulated gene (ISG) expression at the single cell level. We observed that NS segments derived from seasonal H3N2 viruses are more efficient at antagonizing IFN signaling but less effective at suppressing IFN induction, compared to the pdm2009 H1N1 lineage. We compared a collection of NS segments spanning the natural history of the current seasonal IAV lineages and demonstrate long periods of stability in IFN antagonism potential, punctuated by occasional phenotypic shifts. Altogether, our data reveal significant differences in how seasonal and pandemic H1N1 and H3N2 viruses antagonize the human IFN response at the single cell level.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012727"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819392","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":"Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice.","authors":"Nicole L Diggins, Andrew H Pham, Jennifer Mitchell, Christopher J Parkins, Luke Slind, Rebekah Turner, Byeong-Jae Lee, Andrew D Yurochko, Patrizia Caposio, Jay A Nelson, Meaghan H Hancock","doi":"10.1371/journal.ppat.1012285","DOIUrl":"10.1371/journal.ppat.1012285","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) actively manipulates cellular signaling pathways to benefit viral replication. Phosphatidyl-inositol 3-kinase (PI3K)/Akt signaling is an important negative regulator of HCMV replication, and during lytic infection the virus utilizes pUL38 to limit Akt phosphorylation and activity. During latency, PI3K/Akt signaling also limits virus replication, but how this is overcome at the time of reactivation is unknown. Virally encoded microRNAs (miRNAs) are a key component of the virus arsenal used to alter signaling during latency and reactivation. In the present study we show that three HCMV miRNAs (miR-UL36, miR-UL112 and miR-UL148D) downregulate Akt expression and attenuate downstream signaling, resulting in the activation of FOXO3a and enhanced internal promoter-driven IE transcription. A virus lacking expression of all three miRNAs is unable to reactivate from latency both in CD34+ hematopoietic progenitor cells and in a humanized mouse model of HCMV infection, however downregulating Akt restores the ability of the mutant virus to replicate. These findings highlight the negative role Akt signaling plays in HCMV replication in lytic and latent infection and how the virus has evolved miRNA-mediated countermeasures to promote successful reactivation.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012285"},"PeriodicalIF":5.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814729","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":"Is metabolic generalism the Breakfast of Champions for pathogenic Candida species?","authors":"Delma S Childers, Jane Usher","doi":"10.1371/journal.ppat.1012752","DOIUrl":"10.1371/journal.ppat.1012752","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012752"},"PeriodicalIF":5.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814647","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}