TY - JOUR
T1 - Tolerance of MRSA ST239-TW to chlorhexidine-based decolonization; evidence for keratinocyte invasion as a mechanism of biocide evasion
AU - Marbach, Helene
AU - Vizcay-Barrena, Gema
AU - Memarzadeh, Kaveh
AU - Otter, Jonathan A.
AU - Pathak, Smriti
AU - Allaker, Robert P.
AU - Harvey, Richard D.
AU - Edgeworth, Jonathan D.
PY - 2018/10/24
Y1 - 2018/10/24
N2 - Information on genetic determinants of chlorhexidine tolerance (qacA carriage and MIC) in vitro is available, although evidence of the clinical impact and mechanisms remain poorly understood. We investigated why, following chlorhexidine intervention, prevalent epidemic MRSA ST22 and ST36 clones declined at an ICU, whilst an ST239-TW clone did not. The chlorhexidine tolerant ST239-TW phenotypes were assessed for their protein binding, cell adhesion and intracellular uptake potential. Methods : Six ST22, ST36 and ST239-TW bloodstream infection isolates with comparable chlorhexidine MICs were selected from a 2-year outbreak in an ICU at Guy's and St. Thomas’ Hospital. Isolates were tested for fibrinogen and fibronectin binding, and adhesion/internalization into human keratinocytes with and without biocide. Results : Binding to fibrinogen and fibronectin, adhesion and intracellular uptake within keratinocytes (P <0.001) and intracellular survival in keratinocytes under chlorhexidine pressure (ST22 3.18%, ST36 4.57% vs ST239-TW 12.79%; P <0.0001) was consistently higher for ST239-TW. Conclusions : We present evidence that MRSA clones with similarly low in vitro tolerance to chlorhexidine exhibit different in vivo susceptibilities. The phenomenon of S. aureus adhesion and intracellular uptake into keratinocytes could therefore be regarded as an additional mechanism of chlorhexidine tolerance, enabling MRSA to evade infection control measures.
AB - Information on genetic determinants of chlorhexidine tolerance (qacA carriage and MIC) in vitro is available, although evidence of the clinical impact and mechanisms remain poorly understood. We investigated why, following chlorhexidine intervention, prevalent epidemic MRSA ST22 and ST36 clones declined at an ICU, whilst an ST239-TW clone did not. The chlorhexidine tolerant ST239-TW phenotypes were assessed for their protein binding, cell adhesion and intracellular uptake potential. Methods : Six ST22, ST36 and ST239-TW bloodstream infection isolates with comparable chlorhexidine MICs were selected from a 2-year outbreak in an ICU at Guy's and St. Thomas’ Hospital. Isolates were tested for fibrinogen and fibronectin binding, and adhesion/internalization into human keratinocytes with and without biocide. Results : Binding to fibrinogen and fibronectin, adhesion and intracellular uptake within keratinocytes (P <0.001) and intracellular survival in keratinocytes under chlorhexidine pressure (ST22 3.18%, ST36 4.57% vs ST239-TW 12.79%; P <0.0001) was consistently higher for ST239-TW. Conclusions : We present evidence that MRSA clones with similarly low in vitro tolerance to chlorhexidine exhibit different in vivo susceptibilities. The phenomenon of S. aureus adhesion and intracellular uptake into keratinocytes could therefore be regarded as an additional mechanism of chlorhexidine tolerance, enabling MRSA to evade infection control measures.
KW - ST239-TW
KW - Chlorhexidine tolerance
KW - Decolonization
KW - Adhesion
KW - Intracellular uptake
KW - Biocide evasion
U2 - 10.1016/j.jinf.2018.10.007
DO - 10.1016/j.jinf.2018.10.007
M3 - Article
SN - 0163-4453
JO - Journal of Infection
JF - Journal of Infection
ER -
