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Abstract
Bacterial virulence and antibiotic resistance have a significant influence on disease severity and treatment options during bacterial infections. Frequently, the underlying genetic determinants are encoded on mobile genetic elements (MGEs). In the leading human pathogen Staphylococcus aureus, MGEs that contain antibiotic resistance genes commonly do not contain genes for virulence determinants. The phenol-soluble modulins (PSMs) are staphylococcal cytolytic toxins with a crucial role in immune evasion. While all known PSMs are core genome-encoded, we here describe a previously unidentified psm gene, psm-mec, within the staphylococcal methicillin resistance-encoding MGE SCCmec. PSM-mec was strongly expressed in many strains and showed the physico-chemical, pro-inflammatory, and cytolytic characteristics typical of PSMs. Notably, in an S. aureus strain with low production of core genome-encoded PSMs, expression of PSM-mec had a significant impact on immune evasion and disease. In addition to providing high-level resistance to methicillin, acquisition of SCCmec elements encoding PSM-mec by horizontal gene transfer may therefore contribute to staphylococcal virulence by substituting for the lack of expression of core genome-encoded PSMs. Thus, our study reveals a previously unknown role of methicillin resistance clusters in staphylococcal pathogenesis and shows that important virulence and antibiotic resistance determinants may be combined in staphylococcal MGEs.
Highlights
Staphylococci are ubiquitous colonizers of human epithelia and frequent opportunistic pathogens involved in nosocomial infections [1]
The extreme danger associated with Staphylococcus aureus infections is due to the combination of frequent antibiotic resistance, which prevents efficient treatment, with extraordinary virulence, which determines the severity of disease
Our study shows that acquisition of methicillin resistance may be combined with gaining possession of potent toxins by a single event of genetic exchange, which likely represents an important feature accelerating the evolution of methicillin-resistant S. aureus (MRSA) virulence
Summary
Staphylococci are ubiquitous colonizers of human epithelia and frequent opportunistic pathogens involved in nosocomial infections [1]. The severity of a S. aureus infection is to a large extent determined by the toxin repertoire of the infecting strain. S. aureus may produce toxic shock syndrome toxin-1 and other superantigens (enterotoxins), leukocidins, a-toxin, and phenol-soluble modulins (PSMs) [3,4]. Many of these molecules destroy immune cells, thereby contributing considerably to the immune evasion capacity of S. aureus. Some toxins, such as a-toxin and the PSMs, are encoded on the bacterial core genome. While many S. aureus strains produce MGE-encoded toxins, production of a given MGE-encoded toxin is usually limited to a small number of strains and strain-specific [8]
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