A novel resistance mechanism to triclosan that suggests horizontal gene transfer and demonstrates a potential selective pressure for reduced biocide susceptibility in clinical strains of Staphylococcus aureus

被引:81
作者
Ciusa, Maria Laura
Furi, Leonardo
Knight, Daniel [2 ]
Decorosi, Francesca [3 ]
Fondi, Marco [4 ]
Raggi, Carla [5 ]
Rosado Coelho, Joana [6 ]
Aragones, Luis [7 ]
Moce, Laura [7 ]
Visa, Pilar [7 ]
Teresa Freitas, Ana [6 ]
Baldassarri, Lucilla [5 ]
Fani, Renato [4 ]
Viti, Carlo [3 ]
Orefici, Graziella [5 ]
Luis Martinez, Jose [8 ]
Morrissey, Ian [2 ]
Oggioni, Marco Rinaldo [1 ]
机构
[1] Univ Siena, Dipartimento Biotecnol, Policlin Scotte, I-53100 Siena, Italy
[2] Quotient Biores, Fordham, England
[3] Univ Florence, Dipartimento Biotecnol Agrarie, Florence, Italy
[4] Univ Florence, Dipartimento Biol Evolut, Florence, Italy
[5] Ist Super Sanita, Rome, Italy
[6] Eurofins Biolab, Barcelona, Spain
[7] Univ Tecn Lisboa, INESC ID IST, P-1100 Lisbon, Portugal
[8] CSIC, Ctr Nacl Biotecnol, Madrid, Spain
关键词
Biocide; Resistance; Cross-resistance; Horizontal gene transfer; FabI; Triclosan; FATTY-ACID BIOSYNTHESIS; ENOYL REDUCTASE; DRUG TARGET; INHIBITION;
D O I
10.1016/j.ijantimicag.2012.04.021
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The widely used biocide triclosan selectively targets FabI, the NADH-dependent trans-2-enoyl-acyl carrier protein reductase, which is an important target for narrow-spectrum antimicrobial drug development. In relation to the growing concern about biocide resistance, we compared in vitro mutants and clinical isolates of Staphylococcus aureus with reduced triclosan susceptibility. Clinical isolates of S. aureus as well as laboratory-generated mutants were assayed for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) phenotypes and genotypes related to reduced triclosan susceptibility. A potential epidemiological cut-off (ECOFF) MBC of >4 mg/L was observed for triclosan in clinical isolates of S. aureus. These showed significantly lower MICs and higher MBCs than laboratory mutants. These groups of strains also had few similarities in the triclosan resistance mechanism. Molecular analysis identified novel resistance mechanisms linked to the presence of an additional sh-fabI allele derived from Staphylococcus haemolyticus. The lack of predictive value of in-vitro-selected mutations for clinical isolates indicates that laboratory tests in the present form appear to be of limited value. More importantly, detection of sh-fabI as a novel resistance mechanism with high potential for horizontal gene transfer demonstrates for the first time that a biocide could exert a selective pressure able to drive the spread of a resistance determinant in a human pathogen. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
引用
收藏
页码:210 / 220
页数:11
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