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

Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.
Molecular Microbiology (Impact Factor: 4.42). 10/2009; 74(4):956-73. DOI: 10.1111/j.1365-2958.2009.06910.x
Source: PubMed


The 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 substrate-binding 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.

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Available from: Nancy Freitag, Mar 04, 2014
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    • "Additional gene products that contribute to L. monocytogenes pathogenesis are associated with PrsA2 activity; these gene products do not appear to be directly regulated by PrfA but their secretion increases as a result of PrfA activation (Alonzo and Freitag, 2010). These include CtaP, a cysteine-transport associated lipoprotein associated with host cell adhesion, acid resistance, and bacterial membrane integrity (Xayarath et al., 2009), and ChiA, a chitinase that inhibits the expression of host inducible nitric oxide synthase (iNOS) (Chaudhuri et al., 2013). Both of these proteins have been identified as potential substrates of PrsA2 via proteomic analysis (Alonzo and Freitag, 2010). "
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    ABSTRACT: In Gram-positive bacteria, the secretion of proteins requires translocation of polypeptides across the bacterial membrane into the highly charged environment of the membrane-cell wall interface. Here, proteins must be folded and often further delivered across the matrix of the cell wall. While many aspects of protein secretion have been well studied in Gram-negative bacteria which possess both an inner and outer membrane, generally less attention has been given to the mechanics of protein secretion across the single cell membrane of Gram-positive bacteria. In this review, we focus on the role of a post-translocation secretion chaperone in Listeria monocytogenes known as PrsA2, and compare what is known regarding PrsA2 with PrsA homologs in other Gram-positive bacteria. PrsA2 is a member of a family of membrane-associated lipoproteins that contribute to the folding and stability of secreted proteins as they cross the bacterial membrane. PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as swimming motility and bacterial resistance to osmotic stress; however its most critical role may be its requirement for L. monocytogenes virulence and viability within host cells. A better understanding of the role of PrsA2 and PrsA-like homologs will provide insight into the dynamics of protein folding and stability in Gram-positive bacteria and may result in new strategies for optimizing protein secretion as well as inhibiting the production of virulence factors.
    Frontiers in Cellular and Infection Microbiology 02/2014; 4:13. DOI:10.3389/fcimb.2014.00013 · 3.72 Impact Factor
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    • "). A number of studies have investigated the effects of acid shock upon expression of in vivo-relevant genes regulated by PrfA and Sigma B (including bsh, inlA, and inlB) (Phan-Thanh and Mahouin, 1999; Abram et al., 2008; Xayarath et al., 2009; Neuhaus et al., 2013 "
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    ABSTRACT: The foodborne pathogen Listeria monocytogenes has the capacity to survive and grow in a diverse range of natural environments. The transition from a food environment to the gastrointestinal tract begins a process of adaptation that may culminate in invasive systemic disease. Here we describe recent advances in our understanding of how L. monocytogenes adapts to the gastrointestinal environment prior to initiating systemic infection. We will discuss mechanisms used by the pathogen to survive encounters with acidic environments (which include the glutamate decarboxylase and arginine deiminase systems), and those which enable the organism to cope with bile acids (including bile salt hydrolase) and competition with the resident microbiota. An increased understanding of how the pathogen survives in this environment is likely to inform the future design of novel prophylactic approaches that exploit specific pharmabiotics; including probiotics, prebiotics, or phages.
    Frontiers in Cellular and Infection Microbiology 02/2014; 4:9. DOI:10.3389/fcimb.2014.00009 · 3.72 Impact Factor
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    • "This is supported by the finding that the glutamate decarboxylase (GAD) system as the most important ATR component is required for listerial survival in the gastric environment [10], and that the deletion of LisRK, a two-component system (TCS) for signal transduction involved in the regulation of acid resistance, resulted in growth phase-dependent sensitivity to acid stress and a significant reduction in virulence [11]. A further protein linking a low pH-response to listerial virulence is the cysteine transport associated protein CtaP, which is necessary for growth in acidified BHI (pH 5.5) and for virulence after intragastric infection of mice [12]. "
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    ABSTRACT: Background The saprophytic pathogen Listeria monocytogenes has to cope with a variety of acidic habitats during its life cycle. The impact of low-temperature coupled with pH decrease for global gene expression and subsequent virulence properties, however, has not been elucidated. Results qRT-PCR revealed for the first time a transient, acid triggered prfA induction of approximately 4-fold, 5.7-fold, 7-fold and 9.3-fold 60 to 90 min after acid shock of L. monocytogenes at 37°C, 25°C, 18°C, and 10°C, respectively. Comparable data were obtained for seven different L. monocytogenes strains, demonstrating that prfA induction under these conditions is a general response of L. monocytogenes. Transcriptome analysis revealed that the in vivo-relevant genes bsh, clpP, glpD, hfq, inlA, inlB, inlE, lisR, and lplA1 as well as many other genes with a putative role during infection are transiently induced upon acid shock conducted at 25°C and 37°C. Twenty-five genes repressed upon acid shock are known to be down regulated during intracellular growth or by virulence regulators. These data were confirmed by qRT-PCR of twelve differentially regulated genes and by the identification of acid shock-induced genes influenced by σB. To test if up regulation of virulence genes at temperatures below 37°C correlates with pathogenicity, the capacity of L. monocytogenes to invade epithelial cells after acid shock at 25°C was measured. A 12-fold increased number of intracellular bacteria was observed (acid shock, t = 60 min) that was reduced after adaptation to the level of the unshocked control. This increased invasiveness was shown to be in line with the induction of inlAB. Using a nematode infection assay, we demonstrated that Caenorhabditis elegans fed with acid-shocked L. monocytogenes exhibits a shorter time to death of 50% (TD50) of the worms (6.4 days) compared to infection with unshocked bacteria (TD50 = 10.2 days). Conclusions PrfA and other listerial virulence genes are induced by an inorganic acid in a temperature-dependent manner. The data presented here suggest that low pH serves as a trigger for listerial pathogenicity at environmental temperatures.
    BMC Genomics 04/2013; 14(1):285. DOI:10.1186/1471-2164-14-285 · 3.99 Impact Factor
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