Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes

Jovanka M. Voyich, Daniel E. Sturdevant, Kevin R. Braughton, Scott D. Kobayashi, Benfang Lei, Kimmo Virtaneva, David W. Dorward, James M. Musser, Frank R. DeLeo

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis. Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections. We discovered an essential role for the 1hk-1rr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Importantly, the irr gene was highly expressed during human GAS pharyngitis. We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease. The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.

Original languageEnglish (US)
Pages (from-to)1996-2001
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number4
DOIs
StatePublished - Feb 18 2003

ASJC Scopus subject areas

  • General

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