scholarly journals Nonactive-Site Mutations in S. aureus FabI That Induce Triclosan Resistance

ACS Omega ◽  
2020 ◽  
Vol 5 (36) ◽  
pp. 23175-23183
Author(s):  
Robel Demissie ◽  
Pauline Kabre ◽  
Leslie W.-M. Fung
Keyword(s):  
Triclosan Resistance

scholarly journals Triclosan resistance in clinical isolates of Acinetobacter baumannii

2009 ◽  
Vol 58 (8) ◽  
pp. 1086-1091 ◽  
Author(s):  
Yagang Chen ◽  
Borui Pi ◽  
Hua Zhou ◽  
Yunsong Yu ◽  
Lanjuan Li
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Active Efflux ◽  
Low Level ◽  
High Level ◽  
Resistance Rates ◽  
Triclosan Resistance

The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l−1, and the MIC90 was 0.5 mg l−1, lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs ≥1 mg l−1) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1–2 mg l−1) or high level (MICs ≥4 mg l−1). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.

Structural basis of triclosan resistance

2011 ◽  
Vol 174 (1) ◽  
pp. 173-179 ◽  
Author(s):  
N. Jiten Singh ◽  
Dongkyu Shin ◽  
Han Myoung Lee ◽  
Hyun Tae Kim ◽  
Ho-Jin Chang ◽  
...  
Keyword(s):  
Structural Basis ◽  
Triclosan Resistance

Triclosan Resistance in Francisella tularensis: A Site-Directed Mutagenesis Study of the FabI Enzyme

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
N. Silas ◽  
R. Demissie ◽  
L.W.M. Fung
Keyword(s):  
Fatty Acid ◽  
Francisella Tularensis ◽  
Bacterial Resistance ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Enzymatic Reaction ◽  
Site Directed Mutagenesis ◽  
E Coli ◽  
Bacterial Fatty Acid ◽  
Triclosan Resistance

An NADH-dependent enoyl-acyl carrier protein reductase, FabI, catalyzes the final step of bacterial fatty acid biosynthesis, reducing the double bond of trans-2-enoyl-ACP to a single bond forming acyl-ACP. Given its importance in bacterial fatty acid synthesis, FabI has become a recognized drug target. Triclosan, a diphenyl ether, targets the FabI, inhibits its activity, and stops bacterial growth. However, as a consequence of triclosan's popularity, and thus its overuse, bacterial resistance to triclosan has been reported. The mutation G93V in Escherichia coli (E. coli) FabI allows E. coli to resist the action of triclosan. We have identified the equivalent residue of G93 in Francisella tularensis FabI (ftFabI) as A92, and prepared a mutant A92V. E. coli cells, transformed with a plasmid containing the ftFabI-A92V gene, were grown, and the gene was overexpressed. From two growths (6 G of cells), 62 mG of protein, with a histidine tag, at a purity of 85% were obtained. Enzymatic activity was assayed by monitoring the absorbance of NADH at 340 nm. In the presence of triclosan, the wild-type protein was almost completely inhibited after NADH was converted to NAD$^+$ in the enzymatic reaction; however the A92V mutant exhibited similar activity with and without triclosan, demonstrating that triclosan resistance may also develop in Francisella tularensis.

scholarly journals Identification and Characterization of TriABC-OpmH, a Triclosan Efflux Pump of Pseudomonas aeruginosa Requiring Two Membrane Fusion Proteins

2007 ◽  
Vol 189 (21) ◽  
pp. 7600-7609 ◽  
Author(s):  
Takehiko Mima ◽  
Swati Joshi ◽  
Margarita Gomez-Escalada ◽  
Herbert P. Schweizer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Membrane Fusion ◽  
Fusion Proteins ◽  
Efflux Pump ◽  
Divalent Cations ◽  
Constitutive Expression ◽  
Multiple Copies ◽  
High Level ◽  
Triclosan Resistance ◽  
Membrane Fusion Proteins

ABSTRACT Pseudomonas aeruginosa achieves high-level (MIC > 1 mg/ml) triclosan resistance either by constitutive expression of MexAB-OprM, an efflux pump of the resistance nodulation cell division (RND) family, or expression of MexCD-OprJ, MexEF-OprN, and MexJK-OpmH in regulatory mutants. A triclosan-resistant target enzyme and perhaps other mechanisms probably act synergistically with efflux. To probe this notion, we exposed the susceptible Δ(mexAB-oprM) Δ(mexCD-oprJ) Δ(mexEF-oprN) Δ(mexJK) Δ(mexXY) strain PAO509 to increasing triclosan concentrations and derived a resistant strain, PAO509.5. This mutant overexpressed the PA0156-PA0157-PA0158 pump, which only effluxed triclosan, but not closely related compounds, antibiotics, and divalent cations, and was therefore renamed TriABC. Constitutive expression of the triABC operon was due to a single promoter-up mutation. Deletion of two adjacent genes, pcaR and PA0159, encoding transcriptional regulators had no effect on expression of this operon. TriABC is the only P. aeruginosa RND pump which contains two membrane fusion proteins, TriA and TriB, and both are required for efflux pump function. Probably owing to tight transcriptional coupling of the triABC genes, complementation of individual mutations was only partially achievable. Full complementation was only observed when a complete triABC operon was provided in trans, either in single or multiple copies. TriABC associated with OpmH, but not OprM, for assembly of a functional triclosan efflux pump. TriABC is the fifth RND pump in P. aeruginosa shown to efficiently efflux triclosan, supporting the notion that efflux is the primary mechanism responsible for this bacterium's high intrinsic and acquired triclosan resistance.

Triclosan Resistance in a Bacterial Fish Pathogen, Aeromonas salmonicida subsp. salmonicida, is Mediated by an Enoyl Reductase, FabV

2015 ◽  
Vol 25 (4) ◽  
pp. 511-520 ◽  
Author(s):  
Raees Khan ◽  
Myung Hwan Lee ◽  
Haejin Joo ◽  
Yong-Hoon Jung ◽  
Shabir Ahmad ◽  
...  
Keyword(s):  
Aeromonas Salmonicida ◽  
Fish Pathogen ◽  
Enoyl Reductase ◽  
Triclosan Resistance

scholarly journals Clinical Relevance of Type II Fatty Acid Synthesis Bypass in Staphylococcus aureus

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Karine Gloux ◽  
Mélanie Guillemet ◽  
Charles Soler ◽  
Claire Morvan ◽  
David Halpern ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Bacterial Infections ◽  
Impact Resistance ◽  
Acid Synthesis ◽  
Type Ii ◽  
Content Type ◽  
Triclosan Resistance

ABSTRACT The need for new antimicrobials to treat bacterial infections has led to the use of type II fatty acid synthesis (FASII) enzymes as front-line targets. However, recent studies suggest that FASII inhibitors may not work against the opportunist pathogen Staphylococcus aureus, as environmental fatty acids favor emergence of multi-anti-FASII resistance. As fatty acids are abundant in the host and one FASII inhibitor, triclosan, is widespread, we investigated whether fatty acid pools impact resistance in clinical and veterinary S. aureus isolates. Simple addition of fatty acids to the screening medium led to a 50% increase in triclosan resistance, as tested in 700 isolates. Moreover, nonculturable triclosan-resistant fatty acid auxotrophs, which escape detection under routine conditions, were uncovered in primary patient samples. FASII bypass in selected isolates correlated with polymorphisms in the acc and fabD loci. We conclude that fatty-acid-dependent strategies to escape FASII inhibition are common among S. aureus isolates and correlate with anti-FASII resistance and emergence of nonculturable variants.

High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux

2003 ◽  
Vol 31 (2) ◽  
pp. 124-127 ◽  
Author(s):  
Rungtip Chuanchuen ◽  
RoxAnn R. Karkhoff-Schweizer ◽  
Herbert P. Schweizer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Level ◽  
Triclosan Resistance
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