Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA.
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.
Queck
Shu Y
SY
Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Khan
Burhan A
BA
Wang
Rong
R
Bach
Thanh-Huy L
TH
Kretschmer
Dorothee
D
Chen
Liang
L
Kreiswirth
Barry N
BN
Peschel
Andreas
A
Deleo
Frank R
FR
Otto
Michael
M
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D018441:Biofilms / Q000254:growth & development; D055598:Chemical Phenomena; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D006461:Hemolysis; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D020071:Interspersed Repetitive Sequences; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000382:microbiology; D046915:Penicillin-Binding Proteins; D054353:Perforin / Q000235:genetics* / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus; C025971:staphylococcal delta toxin; D054353:Perforin; D003545:Cysteine