Methicillin Resistance Alters the Biofilm Phenotype and Attenuates Virulence in Staphylococcus aureus Device-Associated Infections

Clinical isolates of Staphylococcus aureus can express biofilm phenotypes promoted by the major cell wall autolysin and the fibronectin-binding proteins or the icaADBC-encoded polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG). Biofilm production in methicillin-susceptible S. a...

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Vydáno v:	PLoS pathogens Ročník 8; číslo 4; s. e1002626
Hlavní autoři:	Pozzi, Clarissa, Waters, Elaine M., Rudkin, Justine K., Schaeffer, Carolyn R., Lohan, Amanda J., Tong, Pin, Loftus, Brendan J., Pier, Gerald B., Fey, Paul D., Massey, Ruth C., O'Gara, James P.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.04.2012 Public Library of Science (PLoS)
Témata:	Acetylglucosamine - genetics Acetylglucosamine - metabolism Adaptations Adhesins Adhesins, Bacterial - genetics Adhesins, Bacterial - metabolism Animal models Animals Anti-Bacterial Agents - pharmacology Antibiotic resistance Antibiotics Antibodies Autolysins Bacteriology beta -Lactam antibiotics Biofilms Biofilms - growth & development Biology Cell envelopes Clinical isolates Colonization Data processing Drug resistance Drug resistance in microorganisms Enzymes Equipment Contamination Fibronectin-binding protein Gene Expression Regulation, Bacterial - drug effects Gene Expression Regulation, Bacterial - physiology Genetic aspects Health aspects Hospitals Humans Immunocompromised hosts Immunological tolerance Infection Male MecA protein Medical equipment Medical research Methicillin Methicillin Resistance - drug effects Methicillin Resistance - physiology Methicillin-Resistant Staphylococcus aureus - genetics Methicillin-Resistant Staphylococcus aureus - metabolism Methicillin-Resistant Staphylococcus aureus - pathogenicity Mice Microbial mats Microbiology N-Acetylmuramoyl-L-alanine Amidase - genetics N-Acetylmuramoyl-L-alanine Amidase - metabolism Oxacillin Oxacillin - pharmacology Penicillin Penicillin-Binding Proteins - genetics Penicillin-Binding Proteins - metabolism Phenotype phosphodiesterase Physiological aspects Polysaccharides Polysaccharides, Bacterial - genetics Polysaccharides, Bacterial - metabolism Proteinase Public health Staphylococcus aureus Staphylococcus infections Stress Toxins Transcription Virulence Virulence (Microbiology) United States
ISSN:	1553-7374, 1553-7366, 1553-7374
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Shrnutí:	Clinical isolates of Staphylococcus aureus can express biofilm phenotypes promoted by the major cell wall autolysin and the fibronectin-binding proteins or the icaADBC-encoded polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG). Biofilm production in methicillin-susceptible S. aureus (MSSA) strains is typically dependent on PIA/PNAG whereas methicillin-resistant isolates express an Atl/FnBP-mediated biofilm phenotype suggesting a relationship between susceptibility to β-lactam antibiotics and biofilm. By introducing the methicillin resistance gene mecA into the PNAG-producing laboratory strain 8325-4 we generated a heterogeneously resistant (HeR) strain, from which a homogeneous, high-level resistant (HoR) derivative was isolated following exposure to oxacillin. The HoR phenotype was associated with a R₆₀₂H substitution in the DHHA1 domain of GdpP, a recently identified c-di-AMP phosphodiesterase with roles in resistance/tolerance to β-lactam antibiotics and cell envelope stress. Transcription of icaADBC and PNAG production were impaired in the 8325-4 HoR derivative, which instead produced a proteinaceous biofilm that was significantly inhibited by antibodies against the mecA-encoded penicillin binding protein 2a (PBP2a). Conversely excision of the SCCmec element in the MRSA strain BH1CC resulted in oxacillin susceptibility and reduced biofilm production, both of which were complemented by mecA alone. Transcriptional activity of the accessory gene regulator locus was also repressed in the 8325-4 HoR strain, which in turn was accompanied by reduced protease production and significantly reduced virulence in a mouse model of device infection. Thus, homogeneous methicillin resistance has the potential to affect agr- and icaADBC-mediated phenotypes, including altered biofilm expression and virulence, which together are consistent with the adaptation of healthcare-associated MRSA strains to the antibiotic-rich hospital environment in which they are frequently responsible for device-related infections in immuno-compromised patients.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: CP EMW GBP PDF RCM JPOG. Performed the experiments: CP EMW JKR CRS AJL PT. Analyzed the data: CP EMW JKR CRS PDF RCM GBP BJL JPOG. Wrote the paper: EMW JPOG.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1002626