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Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
Published on: June 25, 2015
Inactivation of DltA modulates virulence factor expression in Streptococcus pyogenes
Kathleen H Cox1, Eduardo Ruiz-Bustos, Harry S Courtney
1Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Plos One
|April 30, 2009
Summary
Mutating the dltA gene in Streptococcus pyogenes reduces M protein expression and virulence. This suggests D-alanine-lipoteichoic acid status influences virulence factor expression, offering a target for new antimicrobial compounds.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- D-alanylated lipoteichoic acid is a key component of gram-positive bacterial cell walls.
- Mutations in the dltABCD operon can reduce bacterial virulence, potentially due to increased antimicrobial peptide binding.
- This study investigates the impact of dltA mutations on virulence factor expression in Streptococcus pyogenes.
Purpose of the Study:
- To investigate the effects of dltA gene mutation on virulence factor expression in Streptococcus pyogenes.
- To understand the mechanism behind the reduced virulence observed in dltA mutants.
- To explore the potential of targeting the dlt operon for novel antimicrobial strategies.
Main Methods:
- Created isogenic Delta dltA mutants in M1T1 Streptococcus pyogenes isolates.
- Quantified M protein levels using immunoblots, flow cytometry, and immunofluorescence.
- Assessed bacterial interactions with human neutrophils (PMN) and growth in human blood.
- Measured transcript levels of virulence genes (emm, sic) and regulatory elements using quantitative RT-PCR.
Main Results:
- Delta dltA mutants showed significantly reduced M protein in cell walls and lower emm transcript levels.
- Mutants exhibited increased complement deposition and enhanced association with polymorphonuclear leukocytes.
- Bacterial growth in whole human blood was reduced in Delta dltA mutants.
- Transcription of sic, encoding an antimicrobial peptide inactivator, was also significantly reduced.
Conclusions:
- Loss of DltA and lipoteichoic acid D-alanine esterification triggers gene regulatory networks impacting virulence factor expression in Streptococcus pyogenes.
- The D-alanine-lipoteichoic acid status critically influences the expression of key streptococcal virulence factors.
- Targeting the dlt operon presents a promising strategy for developing new antimicrobial agents against gram-positive pathogens.
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