Abstract
It has long been a question whether Staphylococcus aureus, a major human pathogen, is able to develop natural competence for transformation by DNA. We previously showed that a novel staphylococcal secondary sigma factor, SigH, was a likely key component for competence development, but the corresponding gene appeared to be cryptic as its expression could not be detected during growth under standard laboratory conditions. Here, we have uncovered two distinct mechanisms allowing activation of SigH production in a minor fraction of the bacterial cell population. The first is a chromosomal gene duplication rearrangement occurring spontaneously at a low frequency [≤10−5], generating expression of a new chimeric sigH gene. The second involves post-transcriptional regulation through an upstream inverted repeat sequence, effectively suppressing expression of the sigH gene. Importantly, we have demonstrated for the first time that S. aureus cells producing active SigH become competent for transformation by plasmid or chromosomal DNA, which requires the expression of SigH-controlled competence genes. Additionally, using DNA from the N315 MRSA strain, we successfully transferred the full length SCCmecII element through natural transformation to a methicillin-sensitive strain, conferring methicillin resistance to the resulting S. aureus transformants. Taken together, we propose a unique model for staphylococcal competence regulation by SigH that could help explain the acquisition of antibiotic resistance genes through horizontal gene transfer in this important pathogen.
Highlights
Staphylococcus aureus, first discovered and described over 130 years ago [1,2], belongs to the low G+C % Gram-positive Bacilli class of Firmicutes that includes Bacillus subtilis and Listeria monocytogenes
A commensal bacterium, often colonizing mammalian nasal cavities [3], S. aureus is a major human pathogen causing a broad spectrum of infections ranging from food poisoning and superficial skin abscesses to more serious diseases such as pneumonia, meningitis, osteomyelitis, septicemia, toxic shock syndrome and sepsis [4]
We propose a model for staphylococcal competence regulation, and discuss its evolutionary differences with the known systems in B. subtilis and Streptococcus species as well as the crucial role competence likely plays in acquisition of antibiotic resistance genes
Summary
Staphylococcus aureus, first discovered and described over 130 years ago [1,2], belongs to the low G+C % Gram-positive Bacilli class of Firmicutes that includes Bacillus subtilis and Listeria monocytogenes. A commensal bacterium, often colonizing mammalian nasal cavities [3], S. aureus is a major human pathogen causing a broad spectrum of infections ranging from food poisoning and superficial skin abscesses to more serious diseases such as pneumonia, meningitis, osteomyelitis, septicemia, toxic shock syndrome and sepsis [4]. [8,9], which carry many of the toxin and antibiotic resistance genes. This indicates that horizontal gene transfer (HGT), occurring in bacteria through multiple mechanisms [10], must play a critical role in the evolution of this major human pathogen. Competence gene orthologues it controls suggested they must be expressed and play a role under certain specific growth conditions.
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