Transcriptional and mutational profiling of an aminoglycoside resistant Pseudomonas aeruginosa small colony variant.
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AbstractPseudomonas aeruginosa is a major causative agent of both acute and chronic infections. Although aminoglycoside antibiotics are very potent drugs to fight such infections, antibiotic failure is steadily increasing mainly due to increasing resistance of the bacteria. Many molecular mechanisms that determine resistance such as acquisition of genes encoding for aminoglycoside-inactivating enzymes or overexpression of efflux pumps have been elucidated. However, there are additional, less-well described mechanisms of aminoglycoside resistance. In this study we have profiled a clinical tobramycin resistant P. aeruginosa strain that exhibited a small colony variant (SCV) phenotype. Both, the resistance and the colony morphology phenotypes were lost upon passaging the isolate under rich medium conditions. Transcriptional and mutational profiling revealed that the SCV harbored activating mutations in the two two-component systems AmgRS and PmrAB. Introduction of these mutations singularly into the type strain PA14 conferred tobramycin and colistin resistance, respectively. However, their combined introduction had an additive effect on the tobramycin resistance phenotype. Activation of the AmgRS system slightly reduced the colony size of the PA14 wild-type, whereas the simultaneous overexpression of gacA, the response regulator of the GacSA two component system, further reduced colony size. In conclusion, we uncovered combinatorial influences of two-component systems on clinically relevant phenotypes, such as resistance and the expression of the SCV phenotype. Our results clearly demonstrate that combined activation of P. aeruginosa two-component systems exhibit pleiotropic effects with unforeseen consequences.
CitationTranscriptional and mutational profiling of an aminoglycoside resistant Pseudomonas aeruginosa small colony variant. 2017 Antimicrob. Agents Chemother.
AffiliationHelmholtz Centre for infection researchGmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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- Mutational activation of the AmgRS two-component system in aminoglycoside-resistant Pseudomonas aeruginosa.
- Authors: Lau CH, Fraud S, Jones M, Peterson SN, Poole K
- Issue date: 2013 May
- Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV) of Pseudomonas aeruginosa.
- Authors: Wei Q, Tarighi S, Dötsch A, Häussler S, Müsken M, Wright VJ, Cámara M, Williams P, Haenen S, Boerjan B, Bogaerts A, Vierstraete E, Verleyen P, Schoofs L, Willaert R, De Groote VN, Michiels J, Vercammen K, Crabbé A, Cornelis P
- Issue date: 2011
- Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa.
- Authors: Schurek KN, Marr AK, Taylor PK, Wiegand I, Semenec L, Khaira BK, Hancock RE
- Issue date: 2008 Dec
- Targeting a bacterial stress response to enhance antibiotic action.
- Authors: Lee S, Hinz A, Bauerle E, Angermeyer A, Juhaszova K, Kaneko Y, Singh PK, Manoil C
- Issue date: 2009 Aug 25
- AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa.
- Authors: Lau CH, Krahn T, Gilmour C, Mullen E, Poole K
- Issue date: 2015 Feb