Abstract
BackgroundCommunity-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immunocompromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors. The genetic basis for this enhanced virulence has yet to be determined. S. aureus possesses a wide variety of virulence factors, the expression of which is carefully coordinated by a variety of regulators. Several virulence regulators have been well characterized, but others have yet to be thoroughly investigated. Previously, we identified the msa gene as a regulator of several virulence genes, biofilm development, and antibiotic resistance. We also found evidence of the involvement of upstream genes in msa function.ResultsTo investigate the mechanism of regulation of the msa gene (renamed msaC), we examined the upstream genes whose expression was affected by its deletion. We showed that msaC is part of a newly defined four-gene operon (msaABCR), in which msaC is a non-protein-coding RNA that is essential for the function of the operon. Furthermore, we found that an antisense RNA (msaR) is complementary to the 5′ end of the msaB gene and is expressed in a growth phase-dependent manner suggesting that it is involved in regulation of the operon.ConclusionThese findings allow us to define a new operon that regulates fundamental phenotypes in S. aureus such as biofilm development and virulence. Characterization of the msaABCR operon will allow us to investigate the mechanism of function of this operon and the role of the individual genes in regulation and interaction with its targets. This study identifies a new element in the complex regulatory circuits in S. aureus, and our findings may be therapeutically relevant.
Highlights
Community-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immunocompromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors
Results msaC is a member of a four-gene operon Previously, we showed that msaC regulates the expression of sarA, and is essential for biofilm formation and protease production [21,22]
The phenotype of the three-Open reading frame (ORF)-deletion mutant was similar to the msaC mutant, with one exception being that the three-ORF-deletion mutant produced significantly more proteases than the msaC mutant (Figure 1B)
Summary
Community-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immunocompromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors. S. aureus possesses a wide variety of virulence factors, the expression of which is carefully coordinated by a variety of regulators. We identified the msa gene as a regulator of several virulence genes, biofilm development, and antibiotic resistance. The ability of S. aureus to infect a variety of tissues is due to its expression of a wide variety of virulence factors. These factors are categorized as surface-associated proteins, secreted proteases, toxins, or immune modulators [3]. Expression of virulence factors in S. aureus is carefully coordinated by a variety of regulators that include trans-acting global regulators, alternative sigma factors, and small non-coding RNAs [3,4,5]. Several other regulators have been identified, though they are not as well characterized (e.g., htrA, ccpA, msrR, and svrR) [17,18,19,20]
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