Differential Gene Activation Protects Streptococcus

The study was published February 6, 2003, in the online edition of the Proceedings of the National Academy of Sciences.

GAS evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). Investigators from the US National Institute of Allergy and Infectious Diseases' (NIAID) Laboratory of Human Bacterial Pathogenesis (Hamilton, MT, USA; www.nih.gov) determined which GAS genes became activated when the bacteria interacted with PMNs.

They found that GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were upregulated during PMN phagocytosis. Genes encoding novel secreted proteins were upregulated, and the proteins were produced during human GAS infections. Furthermore, the researchers discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Significantly, the Irr gene was highly expressed during human GAS pharyngitis.

"This is the first genome-scale look at GAS genes that are differentially expressed during interaction with the human innate immune system,” explained senior author Dr. Frank DeLeo, an investigator in the Laboratory of Human Bacterial Pathogenesis. "We are excited about our findings and how they may lead to further investigation of therapeutics that can protect us from this major human pathogen.”




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NIH/National Institute of Allergy and Infectious Diseases