PLoS Pathogens公共科学图书馆·病原体
PLoS Pathogens(英文缩写 PLOS PATHOG),ISSN 1553-7366,eISSN 1553-7374,中文译名:公共科学图书馆·病原体 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 7.464 | Q1 |
| 2022 | 6.700 | Q1 |
| 2023 | 5.500 | Q1 |
| 2024 | 4.900 | Q1 |
| 2025 | 4.900 | Q1 |
PLoS Pathogens 最新收录文献
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1. A bacterial pangenome association study identifies a role for polyamine metabolism and alkaline tolerance in middle ear infections.
PMID:日期:2026-09-25Infection of the middle ear, or otitis media (OM), is a disease that commonly afflicts children, and Haemophilus influenzae is the most prevalent OM-associated bacterium. We sought new insights into mechanisms of pathogenesis by identifying bacterial genes associated with OM disease. We whole-genome sequenced >200 clinical isolates collected over time from 9 healthy and 12 OM-prone children. Genome analysis first annotated and clustered homologous genes from across assemblies, inferred the phylogeny, and identified closely related set of strains, or clonal lineages, finding both transient and persistent colonization by distinct lineages. Phylogeny-informed association tests then identified 7 strong associations of genes/operons with health or disease. Remarkably, 5 associations were with gene absences and OM, and all 5 had predicted functions consistent with roles in pH homeostasis and nitrogen metabolism, specifically in transport and modification of polyamines. Using a laboratory strain, knockouts of candidate "anti-OM" operon potE-speF were tested. In vitro growth assays varying pH and supplementation with polyamines showed that the presence of potE-speF conferred alkaline sensitivity to cells in the presence of ornithine. Measurements of human middle ear fluid pH found higher alkalinity in specimens where H. influenzae was collected over those with other OM pathogens, supporting the hypothesis that the alkaline middle ear microenvironment in OM arises from or selects for H. influenzae infection. Experiments using a mouse OM model found that absence of potE-speF caused a ~ 63-fold increase in bacterial disease burden in middle ear washes. By contrast, a mouse lung infection model showed no significant difference. We conclude that H. influenzae lacking potE-speF have a selective advantage in OM disease pathogenesis, because these strains thrive in the otherwise hostile alkaline environment that occurs in the middle ears of children.
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2. Functional divergence of the Bhanja virus NSs protein modulates interferon antagonism and viral fitness across divergent lineages.
PMID:日期:2026-09-24Bhanja virus (BHAV) is a tick-borne bandavirus (Family Phenuiviridae) with a broad geographic distribution and documented neuroinvasive capacity, yet its molecular biology remains poorly understood. Within the genus Bandavirus, the non-structural protein NSs functions as the primary antagonist of innate immune responses, although mechanistic details for BHAV remain unknown. We established a reverse genetics platform for BHAV by combining virion RNA sequencing with terminal untranslated region mapping, enabling generation of recombinant viruses and systematic investigation of viral determinants. Using this system, we characterized recombinant BHAV replication in mammalian and arthropod cell lines and demonstrated that interferon competence is a critical determinant of viral replication in mammalian cells. Notably, we observed substantial amino acid divergence within the NSs protein across geographically distinct BHAV isolates, despite higher conservation of other viral proteins. To investigate the functional significance of this variation, we generated recombinant viruses expressing heterologous NSs proteins from African and European isolates. Viruses expressing NSs from ibAr2709 or R1819 isolates exhibited enhanced capacity to suppress interferon-beta induction compared to the prototype IG690 strain, correlating with increased viral protein accumulation in interferon-competent cells. Mechanistic studies revealed that BHAV NSs proteins inhibit interferon induction upstream of IRF3, with ibAr2709 and R1819 NSs showing selective inhibition of TBK1 phosphorylation. However, unlike highly pathogenic bandaviruses such as severe fever with thrombocytopenia syndrome virus (SFTSV), BHAV NSs proteins exhibit comparatively weak antagonism of downstream interferon signalling. In vivo studies using interferon alpha/beta receptor-deficient mice demonstrated that NSs sequence variation influences viral replication in splenic tissue without substantially altering disease phenotype. Together, these findings establish BHAV reverse genetics tools for future investigation and reveal how naturally-occurring NSs divergence modulates innate immune antagonism and viral fitness while maintaining an overall attenuated disease phenotype.
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3. GM000287 is a conserved determinant of serum resistance and virulence in Klebsiella pneumoniae.
PMID:日期:2026-09-24Klebsiella pneumoniae (Kp) is an opportunistic Gram-negative pathogen responsible for severe community- and healthcare-associated infections. Resistance to complement-mediated killing is an important determinant of Kp survival in human serum, yet mechanisms beyond capsular polysaccharide-mediated protection remain incompletely understood. Here, using comparative proteomic approaches, we identified a previously uncharacterized protein, GM000287, as a conserved determinant of serum resistance and virulence in Kp. Human serum exposure induced expression of the bacterial type II secretion system (T2SS), and deletion of the essential T2SS components GspD/GspE increased susceptibility to human serum killing. Importantly, disruption of GspD/GspE attenuated virulence in a murine pneumonia model. Comparative secretome analysis identified GM000287 as a T2SS-associated envelope protein that contributes to serum survival. Loss of GM000287 increased C3b production and factor B deposition on the bacterial surface during human serum exposure, consistent with enhanced alternative pathway amplification. In a murine pneumonia model, deletion of GM000287 reduced bacterial persistence and dissemination and attenuated virulence. Given the minimal bactericidal activity of mouse serum against Kp, indicating an additional role for GM000287 during infection. Importantly, GM000287 was highly conserved among Klebsiella species and broadly distributed among members of the Enterobacteriaceae family, and its contribution to serum resistance was validated in genetically diverse Kp clinical isolates. Together, these findings identify GM000287 as a conserved determinant of human serum resistance and in vivo virulence and reveal distinct contributions of GM000287 to K. pneumoniae fitness across different host-associated environments.
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4. Transcriptional architecture of African swine fever virus.
PMID:日期:2026-09-23African swine fever virus (ASFV), a large double-stranded DNA virus, poses one of the most significant infectious disease threats to the global swine industry. ASFV transcription is particularly complex because of its unique host-independent transcription system. Using nanopore sequencing technology, we accurately identified the viral transcription start and termination sites. Combining direct RNA sequencing with experimental verification strongly supports the presence of long multicistronic RNAs. By combining this information with the viral genome annotation, we identified six novel transcriptional genes with potential functions. Furthermore, we observed transcriptional "read-through" events, in which transcription initiated at a common start site continues beyond typical termination sites, producing multiple RNA transcripts of different lengths. Additionally, via direct RNA nanopore sequencing, we identified m6A and m5C methylation modifications on viral transcripts, which are predominantly distributed at both termini of the viral genome. Compared to unmodified transcripts, modified RNAs have shorter poly(A) tails, indicating a correlation between RNA modification and poly(A) tail length. Further investigation of ASFV transcriptional architecture, "read-through" events, RNA modifications, and candidate genes may improve our understanding of the viral life cycle and pathogenicity and inform the identification of potential antiviral targets.
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5. The translatome of quiescent Plasmodium falciparum gametocytes reveals parasite pyridoxal 5'-phosphate (PLP) biosynthesis is essential for efficient mosquito stage development.
PMID:日期:2026-09-23The ability of Plasmodium falciparum gametocytes to remain quiescent within the vertebrate host but poised for rapid onward development in the mosquito is an adaptation essential to maximise the onward spread of malaria. In this dormant state, mature infectious stage V gametocytes are largely unaffected by most antimalarial drugs and our limited understanding of how gametocytes prepare for mosquito transmission has hindered the identification of new molecular targets for transmission-blocking therapeutics. In this study, we move beyond the total proteome of gametocytes and define the translatome of mature stage V gametocytes using L-azidohomoalanine incorporation into nascent proteins, click chemistry purification and proteomic analysis. We identify the proteins and pathways that gametocytes sustain in preparation for transmission during this dormant period and through genetic disruption, we validate this approach by demonstrating the importance of parasite pyridoxal 5'-phosphate biosynthesis for mosquito transmission.
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6. Metabolic cooperation supports mutual growth between the protozoan parasite Trichomonas vaginalis and dysbiotic vaginal bacteria.
PMID:日期:2026-09-23The protozoan parasite Trichomonas vaginalis, the causative agent of trichomoniasis, is frequently associated with dysbiotic vaginal microbial communities characteristic of bacterial vaginosis (BV). While previous studies have shown that vaginal bacteria can modulate parasite pathogenicity, the metabolic basis underlying this ecological association remains unclear. Here, we investigated whether T. vaginalis and BV-associated bacteria (BVAB) engage in metabolic cooperation that could support their coexistence. Using in vitro co-culture systems, we examined microbial growth under defined nutrient conditions and integrated metabolomic profiling with targeted transcriptional analysis to characterize metabolic interactions between partners. In serum-free defined medium that does not support proliferation of either microorganism alone, T. vaginalis and BVAB exhibited mutualistic growth, indicating that they engage in cooperative metabolic interactions to overcome shared nutritional limitations. Gas chromatography-mass spectrometry revealed a coordinated metabolic shift toward amino acid catabolism during co-culture, with prominent accumulation of ornithine and putrescine linking the arginine dihydrolase (ADH) pathway to polyamine synthesis. Gene expression analyses showed strong upregulation of the parasite carbamate kinase gene during co-culture, implicating enhanced ADH pathway activity in this interaction. Inhibition of polyamine biosynthesis partially impaired the cooperative growth of both microorganisms, further supporting the importance of this metabolic axis. Together, these findings provide experimental evidence that cross-kingdom metabolic cooperation can reciprocally support infection and dysbiosis, highlighting how parasite-microbiome interactions can reshape metabolic networks to overcome environmental constraints and promote their persistence within host-associated microbial ecosystems.
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7. SARS-CoV-2 defective viral genomes from distinct genomic regions drive divergent interferon responses.
PMID:日期:2026-09-23Defective viral genomes (DVGs) are generated during the genomic replication of many RNA viruses. When produced early in infection or supplemented at the onset of infection, DVGs can attenuate viral pathogenesis by stimulating interferon responses and antagonizing wild type (WT) virus replication, highlighting their potential as antiviral therapeutics. However, during natural infection DVGs can exert both antiviral and proviral effects depending on their generation kinetics, species, and abundance, underscoring the need to better understand their roles in viral pathogenesis. Coronaviruses (CoVs) are RNA viruses that ubiquitously generate DVGs, yet the roles of DVGs during CoV infection are largely unknown. In a previous study we investigated SARS-CoV-2 DVG presence in vitro and in patient samples and discovered two major genomic hotspots (A and B) for their generation. Here, we first showed that overall DVG abundance tended to positively correlate with COVID-19 severity, with approximately 40% of DVGs originating from a specific genomic region designated hotspot B. Analysis of a publicly available single-cell RNA-seq dataset revealed that DVGs from hotspot B, but not hotspot A, were associated with elevated interferon responses, suggesting that DVGs derived from different genomic regions vary in their ability to stimulate innate immunity. To test this directly, we constructed two representative DVGs corresponding to hotspots A and B. Both DVGs suppressed the replication of co-infecting WT virus; however, only DVG-B induced robust interferon responses, exceeding those triggered by WT virus alone. This was further confirmed in human precision-cut lung slices. Mechanistically, DVG-B-derived dsRNA exhibited a distinct subcellular distribution compared to WT virus. Complementation with the nucleocapsid (N) partially restored dsRNA organization but did not alter the interferon response. Together, our findings demonstrate that DVGs arising from distinct genomic hotspots differentially regulate interferon responses, and N plays a unique role in regulating dsRNA distribution and interferon responses.
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8. Transposon-insertion sequencing reveals NlpD as a vulnerability in intracellular survival and pathogenesis of Salmonella 4,[5],12:i:.
PMID:日期:2026-09-22Salmonella 4,[5],12:i:- has emerged as a leading cause of non-typhoidal salmonellosis globally, yet the mechanisms governing its intracellular survival and pathogenic adaptation remain unclear. Herein, through transposon-insertion sequencing, we identify nlpD, a peptidoglycan hydrolase activator essential for maintaining membrane stability and facilitating bacterial division, as a critical gene for Salmonella infection. nlpD-deficient Salmonella exhibits significantly diminished survival in both in vitro and in vivo settings. Mechanistically, nlpD deletion disrupts peptidoglycan and lipopolysaccharide homeostasis, rendering Salmonella more vulnerable to oxidative and acidic stresses within phagosomes. Accumulated cell wall components robustly activate the toll-like receptor-mediated NF-κB signaling pathway, driving M1 macrophage polarization and autophagy-lysosomal activation to eliminate intracellular bacteria. An FDA-approved drug screen identifies ketoconazole as an NlpD-targeting compound that reduces bacterial loads in murine models. Our findings establish NlpD as a critical regulator that limits M1-polarized inflammatory responses, highlighting its potential as a therapeutic vulnerability against Salmonella 4,[5],12:i:- infection.
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9. Role of PRMT5 in regulating ferritinophagy during Mycobacterium tuberculosis infection.
PMID:日期:2026-09-22Mycobacterium tuberculosis (Mtb) increases the availability of free iron, resulting in ferroptosis of macrophages to facilitate its survival and dissemination. A critical factor for elevated levels of labile iron is the overt accumulation of nuclear receptor coactivator 4 (NCOA4), which promotes autophagic degradation of ferritin in a process termed ferritinophagy. Here, we identify a novel post-translational modification on NCOA4 that is essential for its interaction with ferritin in the iron-replete condition of Mtb-infected cells. Specifically, protein arginine methyltransferase 5 (PRMT5) confers symmetric dimethylation on NCOA4, which promotes ferritinophagy-mediated ferroptosis. Using loss-of-function studies, we show that PRMT5 is required for lipid peroxidation, bacterial survival, and dissemination in Mtb-infected mice. Additionally, the overexpression of a methylation-deficient mutant of NCOA4 phenocopies the depletion of PRMT5 and reduces ferritinophagy in Mtb-infected cells. Mechanistically, we identify that PRMT5-mediated methylation enhances the cytoplasmic retention of NCOA4 and reduces its nuclear availability. Thus, our findings uncover the key interaction between NCOA4 and ferritin that regulates ferroptosis and mycobacterial survival during infection. Perturbation of this interaction results in reduced Mtb loads and alleviated disease pathology.
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10. A single-cycle, recombinant VSV platform Nipah vaccine cross-protects against Hendra virus in nonhuman primates.
PMID:日期:2026-09-22Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxoviruses that produce severe, often fatal disease in humans and animals. Zoonotic spillover of these henipaviruses from the Pteropid bat natural reservoir occurs near-annually in Southeast Asia and Oceania. Outbreaks of NiV disease frequently exceed case fatality rates of 75%, and person-to-person transmission makes controlling outbreaks in low-resource environments challenging. HeV is less transmissible between humans; however, the overall mortality rate is 57%. Approaches to human vaccine development have largely focused on NiV given the larger case burden, and immunogen selection has centered on display of the NiV attachment (G) or fusion (F) surface glycoproteins. However, experimental vaccines displaying these NiV antigens have failed to uniformly cross-protect against HeV disease in preclinical models. The HeV (G) antigen was shown to cross-protect against both HeV and NiV when delivered in a protein subunit form; however, attempts to utilize mRNA or canarypox vectors failed to achieve equivalent protection. We previously developed and evaluated a single-cycle recombinant vesicular stomatitis virus-vectored vaccine displaying the (G) glycoprotein of Nipah virus strain Bangladesh (NiV-B). This experimental vaccine (G*rVSV∆G-NiV-G) demonstrated ideal characteristics of rapid and durable protection against NiV-B challenge in nonhuman primates. In the present work, we show that the G*rVSV∆G-NiV-G vaccine cross-protects against lethal HeV challenge, with the protective response driven by a balance of both cell-mediated and humoral compartments.