Article
Analysis of the transcriptome of group A Streptococcus in mouse soft tissue infection.
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
American Journal Of Pathology (impact factor:
4.89).
10/2006;
169(3):927-42.
DOI:10.2353/ajpath.2006.060112
pp.927-42
Source: PubMed
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Article: Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies.
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ABSTRACT: The molecular basis for bacterial responses to host signals during natural infections is poorly understood. The gram-positive bacterial pathogen group A Streptococcus (GAS) causes human mucosal, skin, and life-threatening systemic infections. During the transition from a throat or skin infection to an invasive infection, GAS must adapt to changing environments and host factors. To better understand how GAS adapts, we used transcript profiling and functional analysis to investigate the transcriptome of a wild-type serotype M1 GAS strain in human blood. Global changes in GAS gene expression occur rapidly in response to human blood exposure. Increased transcription was observed for many genes that likely enhance bacterial survival, including those encoding superantigens and host-evasion proteins regulated by a multiple gene activator called Mga. GAS also coordinately expressed genes involved in proteolysis, transport, and catabolism of oligopeptides to obtain amino acids in this protein-rich host environment. Comparison of the transcriptome of the wild-type strain to that of an isogenic deletion mutant (DeltacovR) mutated in the two-component regulatory system designated CovR-CovS reinforced the hypothesis that CovR-CovS has an important role linking key biosynthetic, catabolic, and virulence functions during transcriptome restructuring. Taken together, the data provide crucial insights into strategies used by pathogenic bacteria for thwarting host defenses and surviving in human blood.American Journal Of Pathology 03/2005; 166(2):455-65. · 4.89 Impact Factor -
Article: SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides.
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ABSTRACT: Some isolates of the significant human pathogen Streptococcus pyogenes, including virulent strains of the M1 serotype, secrete protein SIC. This molecule, secreted in large quantities, interferes with complement function. As a result of natural selection, SIC shows a high degree of variation. Here we provide a plausible explanation for this variation and the fact that strains of the M1 serotype are the most frequent cause of severe invasive S. pyogenes infections. Thus, protein SIC was found to inactivate human neutrophil alpha-defensin and LL-37, two major antibacterial peptides involved in bacterial clearance. This inactivation protected S. pyogenes against the antibacterial effect of the peptides. Moreover, SIC isolated from S. pyogenes of the M1 serotype was more powerful in this respect than SIC variants from strains of M serotypes 12 and 55, serotypes rarely connected with invasive infections.Journal of Biological Chemistry 06/2003; 278(19):16561-6. · 4.77 Impact Factor -
Article: Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.
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ABSTRACT: Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.Proceedings of the National Academy of Sciences 11/2002; 99(21):13855-60. · 9.68 Impact Factor
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Keywords
Array datasets
coordinated expression
covR mutant strain
experimental mouse soft tissue infection
first global analysis
GAS transcriptome
GAS)-host interactions
isogenic transcriptional regulator knockout mutant
Key discoveries
likely facilitating pathogen persistence
maltodextrin utilization
optimized high-density microarray
oxidative stress genes
putative GAS virulence factors
soft tissues
two-component transcriptional regulators
vaccine development
vaccine research
virulence genes
wild-type serotype M1 GAS strain
