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Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii.
Int J Antimicrob Agents. 2013 Feb; 41(2):117-21.IJ

Abstract

Acinetobacter baumannii is a pathogenic bacterium responsible for a wide range of infections in immunocompromised patients. This study examined the role of insertional inactivation of the adeR gene and its effect on adeABC gene expression along with characterisation of the gyrA and parC mutations involved in ciprofloxacin resistance in three A. baumannii clinical isolates and their derivatives. Primers designed for the detection of adeSRABC detected the presence of ISAba16, which disrupted the adeR gene in strain Ab12M, and ISAba1, which disrupted the same gene in strains Ab18 and Ab209. A second copy of ISAba1 was detected upstream of the adeA gene in Ab209 leading to AdeABC pump expression. AdeIJK pump expression was seen in all of the isolates but was not as significant as AdeABC expression. Minimum inhibitory concentrations of ciprofloxacin were ≥256 mg/L for all of the isolates and a decrease of ≥8-fold was seen following addition of the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine. Fluorometric analysis also demonstrated active efflux, with upregulation of adeIJK and some genes of the adeABC operon in some strains. Sequencing of the quinolone resistance-determining region of the gyrA and parC genes revealed a Ser83→Leu change in the gyrA gene and a novel change of Ser80→Trp in the parC gene of Ab12, Ab12M and Ab209; in Ab18 there was a Ser80→Leu change in parC. This study shows the multifactorial contribution of different mechanisms in A. baumannii leading to ciprofloxacin resistance.

Authors+Show Affiliations

Medical Microbiology, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23217848

Citation

Lopes, B S., and S G B. Amyes. "Insertion Sequence Disruption of adeR and Ciprofloxacin Resistance Caused By Efflux Pumps and gyrA and parC Mutations in Acinetobacter Baumannii." International Journal of Antimicrobial Agents, vol. 41, no. 2, 2013, pp. 117-21.
Lopes BS, Amyes SG. Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii. Int J Antimicrob Agents. 2013;41(2):117-21.
Lopes, B. S., & Amyes, S. G. (2013). Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii. International Journal of Antimicrobial Agents, 41(2), 117-21. https://doi.org/10.1016/j.ijantimicag.2012.08.012
Lopes BS, Amyes SG. Insertion Sequence Disruption of adeR and Ciprofloxacin Resistance Caused By Efflux Pumps and gyrA and parC Mutations in Acinetobacter Baumannii. Int J Antimicrob Agents. 2013;41(2):117-21. PubMed PMID: 23217848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii. AU - Lopes,B S, AU - Amyes,S G B, Y1 - 2012/12/03/ PY - 2012/04/26/received PY - 2012/06/08/revised PY - 2012/08/17/accepted PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/6/12/medline SP - 117 EP - 21 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 41 IS - 2 N2 - Acinetobacter baumannii is a pathogenic bacterium responsible for a wide range of infections in immunocompromised patients. This study examined the role of insertional inactivation of the adeR gene and its effect on adeABC gene expression along with characterisation of the gyrA and parC mutations involved in ciprofloxacin resistance in three A. baumannii clinical isolates and their derivatives. Primers designed for the detection of adeSRABC detected the presence of ISAba16, which disrupted the adeR gene in strain Ab12M, and ISAba1, which disrupted the same gene in strains Ab18 and Ab209. A second copy of ISAba1 was detected upstream of the adeA gene in Ab209 leading to AdeABC pump expression. AdeIJK pump expression was seen in all of the isolates but was not as significant as AdeABC expression. Minimum inhibitory concentrations of ciprofloxacin were ≥256 mg/L for all of the isolates and a decrease of ≥8-fold was seen following addition of the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine. Fluorometric analysis also demonstrated active efflux, with upregulation of adeIJK and some genes of the adeABC operon in some strains. Sequencing of the quinolone resistance-determining region of the gyrA and parC genes revealed a Ser83→Leu change in the gyrA gene and a novel change of Ser80→Trp in the parC gene of Ab12, Ab12M and Ab209; in Ab18 there was a Ser80→Leu change in parC. This study shows the multifactorial contribution of different mechanisms in A. baumannii leading to ciprofloxacin resistance. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/23217848/Insertion_sequence_disruption_of_adeR_and_ciprofloxacin_resistance_caused_by_efflux_pumps_and_gyrA_and_parC_mutations_in_Acinetobacter_baumannii_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(12)00349-4 DB - PRIME DP - Unbound Medicine ER -