Type VI secretion system-associated gene clusters contribute to pathogenesis of Salmonella enterica serovar Typhimurium

Mulder, David T, Cooper, Colin A ORCID: https://orcid.org/0000-0003-2013-8042 and Coombes, Brian K (2012) Type VI secretion system-associated gene clusters contribute to pathogenesis of Salmonella enterica serovar Typhimurium. Infection and Immunity, 80 (6). pp. 1996-2007. ISSN 0019-9567

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The enteropathogen Salmonella enterica serovar Typhimurium employs a suite of tightly regulated virulence factors within the intracellular compartment of phagocytic host cells resulting in systemic dissemination in mice. A type VI secretion system (T6SS) within Salmonella pathogenicity island 6 (SPI-6) has been implicated in this process; however, the regulatory inputs and the roles of noncore genes in this system are not well understood. Here we describe four clusters of noncore T6SS genes in SPI-6 based on a comparative relationship with the T6SS-3 of Burkholderia mallei and report that the disruption of these genes results in defects in intracellular replication and systemic dissemination in mice. In addition, we show that the expression of the SPI-6-encoded Hcp and VgrG orthologs is enhanced during late stages of macrophage infection. We identify six regions that are transcriptionally active during cell infections and that have regulatory contributions from the regulators of virulence SsrB, PhoP, and SlyA. We show that levels of protein expression are very weak under in vitro conditions and that expression is not enhanced upon the deletion of ssrB, phoP, slyA, qseC, ompR, or hfq, suggesting an unknown activating factor. These data suggest that the SPI-6 T6SS has been integrated into the Salmonella Typhimurium virulence network and customized for host-pathogen interactions through the action of noncore genes.

Item Type: Article
Uncontrolled Keywords: animals,bacterial proteins,cell line,female,gene expression regulation, bacterial,genomic islands,macrophages,mice,mice, inbred c57bl,multigene family,salmonella infections, animal,salmonella typhimurium
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User: Pure Connector
Date Deposited: 20 Jan 2014 15:58
Last Modified: 24 Oct 2022 05:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/46123
DOI: 10.1128/IAI.06205-11

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