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PMID: 2158277 Published · ppublish English Journal Article

Analysis of acquired ciprofloxacin resistance in a clinical strain of Pseudomonas aeruginosa.

Antimicrobial agents and chemotherapy ·Vol. 34 ·No. 2 ·1990-02-00 ·Pages 281-6

Masecar BL, Celesk RA, Robillard NJ

Abstract

Decreasing susceptibility to ciprofloxacin was investigated in sequential clinical isolates of Pseudomonas aeruginosa from a patient on ciprofloxacin therapy. All isolates were verified as the same strain by DNA probe. MICs of all quinolones tested were 16- to 32-fold higher for the posttherapy isolates; nonquinolone MICs were unchanged. The isolates were compared by analyses of outer membrane proteins and lipopolysaccharide composition, antimicrobial susceptibilities, measurement of accumulation of ciprofloxacin, and inhibition of DNA gyrase activity by ciprofloxacin and nalidixic acid. No significant changes in outer membrane proteins or ciprofloxacin accumulation were observed; however, both posttherapy isolates lost the long chain O-polysaccharide component of lipopolysaccharide. Preparations of DNA gyrase from the quinolone-resistant posttherapy isolates were 16- to 32-fold less sensitive to inhibition of supercoiling by ciprofloxacin and nalidixic acid than was gyrase from the pretherapy isolate. Inhibition studies on combinations of heterologous gyrase subunits showed that decreased inhibition was conferred by the resistant gyrase A subunits. Thus, acquired resistance to ciprofloxacin in this strain involved an alteration in the A subunit of DNA gyrase and was associated with changes in lipopolysaccharide.

MeSH Terms
Bacterial Outer Membrane Proteins/metabolism Ciprofloxacin/metabolism,pharmacology DNA Topoisomerases, Type II/isolation & purification DNA, Bacterial/genetics DNA, Superhelical/genetics Drug Resistance, Microbial Lipopolysaccharides/pharmacology Microbial Sensitivity Tests Pseudomonas Infections/microbiology Pseudomonas aeruginosa/drug effects,genetics,metabolism Topoisomerase II Inhibitors
Chemicals
Bacterial Outer Membrane Proteins DNA, Bacterial DNA, Superhelical Lipopolysaccharides Topoisomerase II Inhibitors Ciprofloxacin DNA Topoisomerases, Type II
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Masecar B L
Pharmaceutical Division, Miles Inc., West Haven, Connecticut 06516.
Celesk R A
Robillard N J
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.34.2.281
Published
1990-02-00
Pages
281-6
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC171574
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.34.2.281 PMC Full Text View journal details
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