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

M.L. Ciusa; L. Furi; D. Knight; F. Decorosi; M. Fondi; C. Raggi; J.R. Coelho; L. Aragones; L. Moce; P. Visa; A.T. Freitas; L. Baldassarri; R. Fani; C. Viti; G. Orefici; J.L. Martinez; I. Morrissey; M.R. Oggioni

doi:10.1016/j.ijantimicag.2012.04.021

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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

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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

M.L. Ciusa, L. Furi, D. Knight, F. Decorosi, M. Fondi, C. Raggi, J.R. Coelho, L. Aragones, L. Moce, P. Visa, …

International Journal of Antimicrobial Agents, Vol.40(3), pp.210-220

2012

DOI: https://doi.org/10.1016/j.ijantimicag.2012.04.021

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Abstract

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.

Details

Title: 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
Authors/Creators: M.L. Ciusa (Author/Creator) - University of Siena
L. Furi (Author/Creator) - University of Siena
D. Knight (Author/Creator) - Quotient Clinical (United Kingdom)
F. Decorosi (Author/Creator) - University of Florence
M. Fondi (Author/Creator) - University of Florence
C. Raggi (Author/Creator) - Istituto Superiore di Sanità
J.R. Coelho (Author/Creator) - Eurofins Biolab, Barcelona, Spain
L. Aragones (Author/Creator) - Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento
L. Moce (Author/Creator) - Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento
P. Visa (Author/Creator) - Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento
A.T. Freitas (Author/Creator) - Eurofins Biolab, Barcelona, Spain
L. Baldassarri (Author/Creator) - Istituto Superiore di Sanità
R. Fani (Author/Creator) - University of Florence
C. Viti (Author/Creator) - University of Florence
G. Orefici (Author/Creator) - Istituto Superiore di Sanità
J.L. Martinez (Author/Creator) - Centro Nacional de Biotecnología, CSIC, Madrid, Spain
I. Morrissey (Author/Creator) - Quotient Clinical (United Kingdom)
M.R. Oggioni (Author/Creator) - University of Siena
Publication Details: International Journal of Antimicrobial Agents, Vol.40(3), pp.210-220
Publisher: Elsevier
Identifiers: 991005540349607891
Copyright: © 2012 Elsevier B.V. and the International Society of Chemotherapy
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.23 Antibiotics & Antimicrobials; 1.23.173 MRSA and VRE
Web Of Science research areas: Infectious Diseases; Microbiology; Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology