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Inactivation of DltA modulates virulence factor expression in Streptococcus pyogenes.
- Source :
-
PloS one [PLoS One] 2009; Vol. 4 (4), pp. e5366. Date of Electronic Publication: 2009 Apr 29. - Publication Year :
- 2009
-
Abstract
- Background: D-alanylated lipoteichoic acid is a virtually ubiquitous component of gram-positive cell walls. Mutations in the dltABCD operon of numerous species exhibit pleiotropic effects, including reduced virulence, which has been attributed to increased binding of cationic antimicrobial peptides to the more negatively charged cell surface. In this study, we have further investigated the effects that mutating dltA has on virulence factor expression in Streptococcus pyogenes.<br />Methodology/principal Findings: Isogenic Delta dltA mutants had previously been created in two distinct M1T1 isolates of S. pyogenes. Immunoblots, flow cytometry, and immunofluorescence were used to quantitate M protein levels in these strains, as well as to assess their ability to bind complement. Bacteria were tested for their ability to interact with human PMN and to grow in whole human blood. Message levels for emm, sic, and various regulatory elements were assessed by quantitative RT-PCR. Cell walls of Delta dltA mutants contained much less M protein than cell walls of parent strains and this correlated with reduced levels of emm transcripts, increased deposition of complement, increased association of bacteria with polymorphonuclear leukocytes, and reduced bacterial growth in whole human blood. Transcription of at least one other gene of the mga regulon, sic, which encodes a protein that inactivates antimicrobial peptides, was also dramatically reduced in Delta dltA mutants. Concomitantly, ccpA and rofA were unaffected, while rgg and arcA were up-regulated.<br />Conclusions/significance: This study has identified a novel mechanism for the reduced virulence of dltA mutants of Streptococcus pyogenes in which gene regulatory networks somehow sense and respond to the loss of DltA and lack of D-alanine esterification of lipoteichoic acid. The mechanism remains to be determined, but the data indicate that the status of D-alanine-lipoteichoic acid can significantly influence the expression of at least some streptococcal virulence factors and provide further impetus to targeting the dlt operon of gram-positive pathogens in the search for novel antimicrobial compounds.
- Subjects :
- Antigens, Bacterial genetics
Antigens, Bacterial metabolism
Bacterial Outer Membrane Proteins genetics
Bacterial Outer Membrane Proteins metabolism
Base Sequence
Carrier Proteins genetics
Carrier Proteins metabolism
Cell Wall metabolism
DNA Primers genetics
DNA, Bacterial genetics
Gene Expression
Gene Regulatory Networks
Genes, Bacterial
Humans
In Vitro Techniques
Mutation
Neutrophils microbiology
Neutrophils physiology
Operon
Phagocytosis
Streptococcus pyogenes metabolism
Virulence genetics
Virulence physiology
Bacterial Proteins genetics
Bacterial Proteins metabolism
Streptococcus pyogenes genetics
Streptococcus pyogenes pathogenicity
Teichoic Acids metabolism
Virulence Factors genetics
Virulence Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 4
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 19401780
- Full Text :
- https://doi.org/10.1371/journal.pone.0005366