1887

Abstract

Pathogenic micro-organisms have evolved many strategies to counteract the antimicrobial peptides (AMPs) that they encounter upon entry into host systems. These strategies play vital roles in the virulence of pathogenic micro-organisms. The serovar Typhimurium genome has a gene cluster consisting of and genes, which encode a putative ATP-binding cassette (ABC) transporter. Our study shows that these genes constitute an operon. We deleted the gene, which encodes the ATPase component of the putative ABC transporter. The Δ strain showed increased sensitivity to protamine, melittin, polymyxin B, human defensin (HBD)-1 and HBD-2, and was compromised in its capacity to proliferate inside activated macrophages and epithelial cells. Inside Intestine 407 cells, was found to co-localize with human defensins HD-5 and HBD-1; this suggests that the ability to counteract AMPs in the intracellular milieu is important for . In a murine typhoid model, the Δ strain displayed decreased virulence when infected intragastrically. These findings suggest that the putative transporter encoded by the operon is involved in counteracting AMPs, and that it contributes to the virulence of .

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2008-02-01
2019-11-20
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vol. , part 2, pp. 666-678

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Susceptibility the of the Δ strain (open circles) to different concentrations of melittin (a) and polymyxin B (b). The assay was done as described in Methods. * <0.01 (Student’s test). Filled circles, WT.

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Intracellular proliferation of the Δ in PMA (100 ng ml )-activated U937 cells. The assay was done as described in Methods. ** <0.005 (Student’s test).

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Co-localization of with HD-5 (green) inside Intestine 407 cells at 2 h after infection. The experiment was done as described in Methods. Bar, 2 μm. Red, LPS.

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Primers used in this study.

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Amino acid sequence comparison of proteins encoded by the yej operon with components of other peptide transporters of .

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Eukaryotic cell lines used in this study.

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