PLoS Pathogens

Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrP Sc . Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD con…

Porcine epidemic diarrhea virus (PEDV) poses a significant threat to the global swine industry; however, the host factors that support its replication remain poorly understood. Our previous study showed that myeloid cell leukemia 1 (MCL1) is a pro-PEDV replication cellular factor through genome-scale CRISPR-Cas9-knockout (KO) screening. Nevertheless, the molecular mechanism whereby MCL1 promotes …

Praziquantel (PZQ) is currently the only agent for treating schistosomiasis, but it is plagued by suboptimal efficacy to juvenile parasites, looming drug resistance, and inability to prevent reinfection. Thioredoxin glutathione reductase (TGR) is regarded as a promising therapeutic target due to its essential role in maintaining schistosome redox homeostasis. Herein, the crystal structures of Sch…

Interleukin-17-producing T helper (Th17) CD4 + T cells are highly susceptible to HIV infection and are depleted early in people living with HIV. Here, we investigated whether systemic Th17 cell levels prior to HIV infection are associated with subsequent HIV disease progression. We analyzed archived cryopreserved peripheral blood mononuclear cells (PBMCs) collected within one year prior to HIV ac…

Duck plague, caused by the alphaherpesvirus Duck plague virus (DPV), is an acute, hemorrhagic, and economically devastating disease of waterfowl. DPV infection induces severe immunosuppression, yet the mechanisms by which this pathogen subverts host innate immunity, particularly through manipulation of the host ubiquitin system, remain unclear. The cGAS-STING signaling pathway is a cornerstone of…

Bordetella pertussis causes whooping cough (pertussis), a respiratory infectious disease that is resurgent despite high vaccine coverage. Research on the mechanisms of immunity to B. pertussis have demonstrated protective roles for innate immune cells, antibodies and T cells in immunity induced by natural infection. Studies in animal models have demonstrated that IL-17-secreting respiratory tissu…

Shiga toxin (Stx)-producing Escherichia coli (STEC) is a major cause of food-borne illnesses, and disease severity correlates with the production of Shiga toxins. While clinical symptoms such as bloody diarrhea and haemolytic uremic syndrome have been attributed to Stx, its contribution to bacterial fitness is not well understood. Here, we demonstrate that Stx2 enhances STEC colonization of the z…

Several pathogens are known to affect the respiratory tract of pigs resulting in decreased health and welfare. Porcine parainfluenza virus 1 (PPIV1) and swine orthopneumovirus (SOV) have been identified as novel viruses in pigs. The pathogenicity of PPIV1 has been investigated experimentally by one research group, whereas SOV is yet to be studied. In this experimental trial, two groups of eight p…

We report the identification and cryoEM structure of the Francisella protein FTN_1118, a previously uncharacterized 13 kDa periplasmic protein unique to the Francisella genus. The protein was serendipitously discovered during purification of Francisella type VI secretion system (T6SS) effector proteins and is hereby designated as FPM13 (Francisella Periplasmic Metalloprotein, 13 kDa) based on its…

Respiratory syncytial virus (RSV) infection is the major cause of severe respiratory illnesses in infants and older adults. RSV forms phase-separated biomolecular condensates called inclusion bodies (IBs), which serve as hubs for viral replication. However, the contribution of IBs to host immune response evasion remains elusive. We report that RSV IBs protect viral RNA from the 2'-5' oligoadenyla…

Candida auris is an emerging, multidrug-resistant fungal pathogen that causes healthcare-associated outbreaks and life-threatening systemic infections. Unlike other Candida species, C. auris exhibits a distinct capacity for persistent skin colonization. In this review, we summarize our current understanding of clinical risk factors and host-microbe interactions that underlie C. auris skin coloniz…

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple short and long noncoding RNAs which contribute to viral latency, persistence, host gene regulation, and immune evasion. The Antisense-to-Latency Transcript (ALT) is a ~ 10 kb long noncoding RNA (lncRNA) located on the opposite strand of the major latency-associated region encoding the latency associated nuclear antigen, vCyclin, vFLI…

Transmission bottlenecks are defined by the number of unique virions or genotypes that establish an infection, and they restrict viral diversity that passes from one infected host to another. Previous work identified a tight transmission bottleneck for seasonal influenza A virus (IAV) based on analysis of 43 household pairs, largely from a single A(H3N2) predominant season. While many viral and h…

The nucleoid-associated protein Fis is a key transcriptional regulator in Gram-negative bacteria that supports rapid adaptation to environmental changes. In Yersinia pseudotuberculosis, Fis plays a critical, yet poorly understood role in virulence. Here, we present a comparative transcriptomic analysis of Y. pseudotuberculosis wild type and fis deletion mutant at environmental (25°C) and host-rel…

The kinetoplast incorporates the large mitochondrial genome present in the eponymous Kinetoplastida. Trypanosoma brucei is an African trypanosome that can lose kinetoplast DNA (kDNA), however, when the nuclear-encoded gamma subunit of the mitochondrial F1FO-ATP synthase (γATPase) is mutated. These mutations, analogous to a broken camshaft at the core of the ATP synthase rotary motor, are associat…

Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-C…

Entomopathogenic fungi serve as powerful regulators of insect populations in nature. However, how immune effectors combat fungal pathogens remains incompletely understood. We employ Drosophila melanogaster as a genetically tractable model to dissect immune defense mechanisms against diverse fungal pathogens. We show that the Toll pathway is the key determinant of immunity against all species test…

Helminth infections in grazing ruminants are of major concern for animal welfare and cause substantial economic losses, prompting the widespread use of ivermectin (IVM). The emergence of IVM resistance, driven by complex and poorly understood mechanisms, increasingly compromises treatment efficacy. Drug efflux transporters, particularly P-glycoproteins (PGPs), are suspected to contribute to resis…

Epstein-Barr virus (EBV) is associated with multiple malignancies including Burkitt lymphoma (BL), Hodgkin's lymphomas, nasopharyngeal carcinomas (NPC), and gastric cancers. Canonically, EBV positive tumors display latent gene expression programs that are difficult to target pharmacologically. To overcome this hurdle, lytic reactivation therapies have been developed based on HDAC inhibition with …