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...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5d1a1b2700244c6ea7c251e0775fdae1 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5d1a1b2700244c6ea7c251e0775fdae1 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5d1a1b2700244c6ea7c251e0775fdae12021-11-18T06:04:34ZMethicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections.1553-73661553-737410.1371/journal.ppat.1002626https://doaj.org/article/5d1a1b2700244c6ea7c251e0775fdae12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496652/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Clinical 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.Clarissa PozziElaine M WatersJustine K RudkinCarolyn R SchaefferAmanda J LohanPin TongBrendan J LoftusGerald B PierPaul D FeyRuth C MasseyJames P O'GaraPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 4, p e1002626 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Clarissa Pozzi Elaine M Waters Justine K Rudkin Carolyn R Schaeffer Amanda J Lohan Pin Tong Brendan J Loftus Gerald B Pier Paul D Fey Ruth C Massey James P O'Gara Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| description |
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. |
| format |
article |
| author |
Clarissa Pozzi Elaine M Waters Justine K Rudkin Carolyn R Schaeffer Amanda J Lohan Pin Tong Brendan J Loftus Gerald B Pier Paul D Fey Ruth C Massey James P O'Gara |
| author_facet |
Clarissa Pozzi Elaine M Waters Justine K Rudkin Carolyn R Schaeffer Amanda J Lohan Pin Tong Brendan J Loftus Gerald B Pier Paul D Fey Ruth C Massey James P O'Gara |
| author_sort |
Clarissa Pozzi |
| title |
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| title_short |
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| title_full |
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| title_fullStr |
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| title_full_unstemmed |
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. |
| title_sort |
methicillin resistance alters the biofilm phenotype and attenuates virulence in staphylococcus aureus device-associated infections. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/5d1a1b2700244c6ea7c251e0775fdae1 |
| work_keys_str_mv |
AT clarissapozzi methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT elainemwaters methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT justinekrudkin methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT carolynrschaeffer methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT amandajlohan methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT pintong methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT brendanjloftus methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT geraldbpier methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT pauldfey methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT ruthcmassey methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections AT jamespogara methicillinresistancealtersthebiofilmphenotypeandattenuatesvirulenceinstaphylococcusaureusdeviceassociatedinfections |
| _version_ |
1718424604273278976 |