d -Alanylation of Lipoteichoic Acid Contributes to the Virulence of Streptococcus suis

Abstract

We generated by allelic replacement a ⌬dltA mutant of a virulent Streptococcus suis serotype 2 field strain and evaluated the contribution of lipoteichoic acid (LTA) D-alanylation to the virulence traits of this swine pathogen and zoonotic agent. The absence of LTA D-alanylation resulted in increased susceptibility to the action of cationic antimicrobial peptides. In addition, and in contrast to the wild-type strain, the ⌬dltA mutant was efficiently killed by porcine neutrophils and showed diminished adherence to and invasion of porcine brain microvascular endothelial cells. Finally, the ⌬dltA mutant was attenuated in both the CD1 mouse and porcine models of infection, probably reflecting a decreased ability to escape immune clearance mechanisms and an impaired capacity to move across host barriers. The results of this study suggest that LTA D-alanylation is an important factor in S. suis virulence.

In VitroCharacterization of the Microglial Inflammatory Response toStreptococcus suis, an Important Emerging Zoonotic Agent of Meningitis

“…On the other hand, the capsule seems to be critical for modulating production of proinflammatory mediators, as the CPS Ϫ mutant induced the release of significantly higher levels of all proinflammatory mediators. These findings support the assumption that several cell wall components, such as lipoteichoic acid (LTA), peptidoglycan (PG), and lipoproteins, partially masked by the capsule are potent proinflammatory inducers, as recently suggested (24,25,70). Finally, as low production of IP-10 for capsulated S. suis strains in comparison to the CPS Ϫ mutant was also noted, we hypothesize that the CPS might influence the onset of the adaptive inflammatory response, as recently shown for dendritic cells (Lecours et al, submitted).…”

Development of an integration mutagenesis system inLactobacillus gasseri

“…27 Moreover, pathogenic dlt knockout derivatives exhibited decreased adhesion to mammalian cells which further substantiates the role of d-alanine substitution in adherence capacity. 28,29 However, deletion of the phosphoglycerol transferase gene, which potentially abolishes the poly-Gro-P backbone would eliminate both the cationic and anionic charges associated therewith. Thus, the inhibited adhesion phenotype observed in ltaS knockout mutants could be attributed to the lowered cation content on the cell surface or be suitably explained by the general removal of charge from the cell surface.…”

Regulation of bacterial virulence gene expression by cell envelope stress responses

“…Consistent with this, dlt null mutants of Gram-positive pathogens have increased sensitivity to CAMPs, increased killing by human neutrophils and reduced virulence in animal models of infection. [156][157][158][159][160][161][162][163][164] The dlt operon is also one of the best examples of virulence genes controlled by ESRs in Gram-positive bacteria. Even though many Gram-positive ESRs are widely conserved, their target genes can vary significantly between species.…”