Listeria monocytogenes CtaP is a multifunctional cysteine transport‐associated protein required for bacterial pathogenesis

Abstract

SummaryThe bacterial pathogen Listeria monocytogenes survives under a myriad of conditions in the outside environment and within the human host where infections can result in severe disease. Bacterial life within the host requires the expression of genes with roles in nutrient acquisition as well as the biosynthesis of bacterial products required to support intracellular growth. A gene product identified as the substratebinding component of a novel oligopeptide transport system (encoded by lmo0135) was recently shown to be required for L. monocytogenes virulence. Here we demonstrate that lmo0135 encodes a multifunctional protein that is associated with cysteine transport, acid resistance, bacterial membrane integrity and adherence to host cells. The lmo0135 gene product (designated CtaP, for cysteine transport associated protein) was required for bacterial growth in the presence of low concentrations of cysteine in vitro, but was not required for bacterial replication within the host cytosol. Loss of CtaP increased membrane permeability and acid sensitivity, and reduced bacterial adherence to host cells. ctaP deletion mutants were severely attenuated following intragastric and intravenous inoculation of mice. Taken together, the data presented indicate that CtaP contributes to multiple facets of L. monocytogenes physiology, growth and survival both inside and outside of animal cells.

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

“…ctaP deletion mutants also display significant attenuation after intragastric and intravenous inoculation of mice. 55 LapB is a SrtA-anchored LPXTG protein that was identified using comparative genomics. 56 lapB is absent from nonpathogenic Listeria species, and its expression was shown to be positively regulated by PrfA and highly increased in infected mouse spleens.…”

Control of Clostridium difficile Physiopathology in Response to Cysteine Availability

“…Additionally, genes involved in sulfur metabolism are induced when Mycobacterium tuberculosis, Yersinia ruckeri, Staphylococcus aureus, and Nesseiria meningitidis interact with human cells (22)(23)(24). In addition, loss-of-function mutations in genes involved in cysteine biosynthesis or degradation affect the virulence for some of these pathogens (23)(24)(25)(26). Finally, the master regulator of cysteine metabolism in S. aureus, CymR, plays an important role in both the stress response and the control of bacterial virulence (27).…”

Listeria monocytogenes Uses Listeria Adhesion Protein (LAP) To Promote Bacterial Transepithelial Translocation and Induces Expression of LAP Receptor Hsp60

“…Ami, an autolysin amidase, contributes to adhesion via interaction with an unknown host receptor (41). CtaP, a cysteine transport-associated protein, is also involved in adhesion to host cells (61), and LapB, a newly identified PrfA-regulated virulence protein, is involved in both adhesion to and invasion of host cells (49).…”