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PMID:20001858
| 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 |
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| 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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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0009405 : pathogenesis |
ECO:0000315: |
P |
saeR is part of a two component system saeR/S in Staphylococcus aureus that performs many functions. Among those functions, saeRS aids in pathogenesis by increasing the virulence. In this experiment, the USA300 strain, both a wt and a deltasaeRS, were injected into mice. The researchers recorded the process of the infection, to see if there was a difference between the wild type and mutant strains. Referring to Figure 2B, only a certain percentage [about 50%] of the mice that were injected became infected versus 100% of the wild type strain. Also, none of the mice that had the mutant strain resulted in necrosis of the skin. In figure 2E, the mouse survival percentanges were significantly higher in the mutant strain than in the wild type strain, meaning that with the deletion, it took a lot longer for the infection to become lethal to some of the mice that were infected. Furthermore, based on this evidence, I believe that the saeR/S system functions to help increase the virulence of the Staphylococcus aureus USA 300 strain. |
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References
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