Porcine diarrhea and gastroenteritis are major causes of piglet mortality that result in devastating economic losses to the industry. A plethora of pathogens can cause these diseases, with the transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC) being two of the most salient. In the December 2017 issue of Proteomics Clinical Aplications, Xia and colleagues used comparative proteomics to shed light on how these microbes interact to cause severe disease . The authors discovered that TGEV induces an epithelial-mesenchymal transition-like phenotype that augments cell adhesion proteins mediating the attachment of ETEC to intestinal epithelial cells. Moreover, coinfection was found to modulate several host proteins that could bolster pathogen persistence. Importantly, the authors observed that ETEC suppresses the production of inflammatory cytokines induced by TGEV, which may in turn promote the long-term survival of both microbes.

To colonize mammalian phagocytic cells, the parasite Leishmania remodels phagosomes into parasitophorous vacuoles that can be either tight-fitting individual or communal. The molecular and cellular bases underlying the biogenesis and functionality of these two types of vacuoles are poorly understood. In this study, we investigated the contribution of host cell Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor proteins to the expansion and functionality of communal vacuoles as well as on the replication of the parasite. The differential recruitment patterns of Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor to communal vacuoles harboring L. amazonensis and to individual vacuoles housing L. major led us to further investigate the roles of VAMP3 and VAMP8 in the interaction of Leishmania with its host cell. We show that whereas VAMP8 contributes to optimal expansion of communal vacuoles, VAMP3 negatively regulates L. amazonensis replication, vacuole size, as well as antigen cross-presentation. In contrast, neither proteins has an impact on the fate of L. major . Collectively, our data support a role for both VAMP3 and VAMP8 in the development and functionality of L. amazonensis -harboring communal parasitophorous vacuoles.

To colonize host phagocytes, Leishmania metacyclic promastigotes subvert host defense mechanisms and create a specialized intracellular niche adapted to their replication. This is accomplished through the action of virulence factors, including the surface coat glycoconjugate lipophosphoglycan.

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To colonize macrophages, Leishmania promastigotes employ virulence factors, including lipophosphoglycan (LPG), to impair host cell processes. Whereas previous studies revealed that Leishmania alters signaling axes that regulate mitochondrial function, scarce attention has been paid to the characterization of host cell mitochondrial metabolism during Leishmania infection and to the effectors involved therein. In this study, we addressed the hypothesis that L. donovani modulates host cell mitochondrial metabolism and function in an LPG-dependent manner. To this end, we infected bone-marrow-derived macrophages with metacyclic promastigotes and we assessed the expression kinetics of host cell nuclear and mitochondrial genes that control mitochondrial biogenesis, and we measured host mitochondrial metabolic fluxes. We found that host cell nuclear and mitochondrial genes that control mitochondrial biogenesis are upregulated in an LPG-dependent manner. We also observed that IRG-1, the enzyme that synthesizes itaconate, is highly induced during infection in an LPG-dependent manner and this response was independent of endosomal TLRs. We next found that L. donovani induces a doubling in the mtDNA/nDNA ratio in an endosomal TLRs and IFNAR-dependent manner, suggesting that L. donovani promotes host mitochondrial biogenesis in an inflammatory context. Metabolic flux analyzes showed that the OCR/ECAR ratio is modulated multiple times during infection, independently of β-oxidation, suggesing that L. donovani promastigotes induce the Warburg effect to promote energetic metabolic changes. Collectively, our data indicate that L. donovani alters host cell mitochondrial dynamics during the colonization process.