AUTHOR=Cestero Juan J. , Castanheira Sónia , Pucciarelli M. Graciela , García-del Portillo Francisco 

TITLE=A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.633701

DOI=10.3389/fmicb.2021.633701

ISSN=1664-302X

ABSTRACT=Horizontal gene transfer has shaped the evolution of Salmonella enterica serovar Typhimurium as pathogen. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Here, we report a novel S. 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. Based on the presence of this domain, we hypothesized a role of this S. Typhimurium protein in PG metabolism. This protein, which we named ScwA for Salmonella cell wall-related regulator-A, controls positively the levels of the murein lytic transglycosylase MltD. In addition, ScwA modulates at lower extent the levels of other enzymes that hydrolyze the PG lattice, including a soluble lytic tranglycosylase (Slt), the amidase AmiC, and a few endo- and carboxypeptidases (NlpC, PBP4 and AmpH). The scwA gene has lower G+C content than the genomic average (43.1% vs 52.2%), supporting its acquisition by horizontal transfer. ScwA is located in the periplasm, stabilized by two disulfide bridges in conserved cysteines, produced preferentially by resting non-growing bacteria and down-regulated following entry of the pathogen into eukaryotic cells. ScwA deficiency however results in a hypervirulent phenotype in the murine typhoid model. Based on these findings, we conclude that ScwA may be exploited by S. Typhimurium to ensure cell envelope homeostasis along the infection and to prevent host overt damage. 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.