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PMID:20001858

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Citation

Nygaard, TK, Pallister, KB, Ruzevich, P, Griffith, S, Vuong, C and Voyich, JM (2010) SaeR binds a consensus sequence within virulence gene promoters to advance USA300 pathogenesis. J. Infect. Dis. 201:241-54

Abstract

This investigation examines the role of the SaeR/S 2-component system in USA300, a prominent circulating clone of community-associated methicillin-resistant Staphylococcus aureus. Using a saeR/S isogenic deletion mutant of USA300 (USA300DeltasaeR/S) in murine models of sepsis and soft-tissue infection revealed that this sensory system is critical to pathogenesis of USA300 during both superficial and invasive infection. Oligonucleotide microarray and real-time reverse-transcriptase polymerase chain reaction identified numerous extracellular virulence genes that are down-regulated in USA300DeltasaeR/S. Unexpectedly, an up-regulation of mecA and mecR1 corresponded to increased methicillin resistance in USA300DeltasaeR/S. 5'-RACE analysis defined transcript start sites for sbi, efb, mecA, lukS-PV, hlb, SAUSA300_1975, and hla, to underscore a conserved consensus sequence within promoter regions of genes under strong SaeR/S transcriptional regulation. Electrophoretic mobility shift assay experiments illustrated direct binding of SaeR(His) to promoter regions containing the conserved consensus sequence. Collectively, the findings of this investigation demonstrate that SaeR/S directly interacts with virulence gene promoters to significantly influence USA300 pathogenesis.

Links

PubMed PMC2798008 Online version:10.1086/649570

Keywords

Animals; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Community-Acquired Infections/microbiology; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Gene Expression Profiling; Humans; Methicillin-Resistant Staphylococcus aureus/genetics; Methicillin-Resistant Staphylococcus aureus/pathogenicity; Mice; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic/genetics; Sequence Deletion; Soft Tissue Infections/microbiology; Up-Regulation; Virulence Factors/metabolism

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