This evasion mechanism is consistent with the diminished nuclear translocation of the NF-kB p65 subunit and release of proinflammatory cytokines observed in cells persistently infected with S. An augmented cleavage of the D-Glu- mDap bond in the PG of intra-phagosomal bacteria was postulated to attenuate stimulation of intracellular host defense receptors like the nucleotide oligomerization domain (NOD)-family NOD1 receptor ( Caruso et al., 2014 Philpott et al., 2014 Rico-Pérez et al., 2016). Typhimurium) increases the production of EcgA, an D,L-endopeptidase that cleaves the D-glutamic acid- meso-diaminopimelic acid (D-Glu- mDap) bond in stem peptides of the PG and that is required for virulence in the mouse typhoid model ( Rico-Perez et al., 2016). enterica, specifically in the peptidoglycan (PG). Recent evidence also supports the existence of additional modifications in the cell envelope of intracellular S. Some of these changes involve alterations in the lipid-A portion of the lipopolysaccharide (LPS), modifications that are orchestrated by the functionally interconnected regulatory systems PhoP-PhoQ and PmrA-PmrB ( Chen and Groisman, 2013 Dalebroux and Miller, 2014), both required for virulence. enterica to build a specialized phagosome and to adapt to the intracellular lifestyle, this pathogen modifies the cell envelope to withstand varied host cell defenses, including antimicrobial peptides. The genes encoding structural components of these T3SS apparatuses and effector proteins are present only in pathogenic bacteria and display features that reveal acquisition by horizontal gene transfer, being the more prominent a different G+C% than the genomic average ( Gyles and Boerlin, 2014 Ilyas et al., 2017).īesides effector proteins exploited by S. These virulence-related T3SS allow bacteria to invade and survive inside phagocytic and non-phagocytic cells ( Galan, 2001 Galan et al., 2014) by mechanisms involving translocation of effector proteins into the infected host cell that subvert vesicular trafficking and cytoskeletal dynamics ( de Souza Santos and Orth, 2015 Personnic et al., 2016 Jennings et al., 2017). enterica evolved as a pathogen following acquisition of genomic islands that encode specialized type III secretion systems (T3SS). enterica, with many of them exhibiting distinct host range ( Baumler and Fang, 2013), they share some traits in their pathogenicity strategies. Despite the large diversity of subspecies and serovars known in S. Non-Typhoidal Salmonella Invasive Disease Collaborators, 2019). Salmonella enterica is one of the most successful bacterial pathogens known causing with high morbidity and mortality food-borne diseases in humans and livestock ( Ao et al., 2015 Haselbeck et al., 2017 Gibani et al., 2018 G. This role could be accomplished by controlling the production or stability of a reduced number of peptidoglycan hydrolases whose activities result in the release of PG fragments. Typhimurium to ensure cell envelope homeostasis along the infection and to prevent host overt damage. Based on these findings, we conclude that ScwA may be exploited by S. ScwA deficiency, however, results in a hypervirulent phenotype in the murine typhoid model. ScwA is located in the periplasm, stabilized by two disulfide bridges, produced preferentially in stationary phase and down-regulated following entry of the pathogen into eukaryotic cells.
52.2%), supporting acquisition by horizontal transfer. The scwA gene has lower G+C content than the genomic average (43.1 vs.
In addition, the levels of other enzymes that cleave bonds in the PG lattice were affected in a mutant lacking ScwA, including a soluble lytic tranglycosylase (Slt), the amidase AmiC, and a few endo- and carboxypeptidases (NlpC, PBP4, and AmpH). This protein, which we named ScwA for Salmonella cell wall-related regulator- A, controls positively the levels of the murein lytic transglycosylase MltD. Based on the presence of such domain, we hypothesized a role of this S. Here, we report a novel serovar Typhimurium protein that is absent in non-pathogenic bacteria and bears a LprI functional domain, first reported in a Mycobacterium tuberculosis lipoprotein conferring lysozyme resistance. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Horizontal gene transfer has shaped the evolution of Salmonella enterica as pathogen.
Graciela Pucciarelli 1,2,3 and Francisco García-del Portillo 1*
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