Lipopolysaccharide Alterations Responsible for Combined Quinolone and β-Lactam Resistance in <i>Pseudomonas aeruginosa</i>

Abstract

Resistant variants of three clinical Pseudomonas aeruginosa isolates were obtained in the presence of aztreonam. The variants exhibited a four- to eightfold increase in the minimal inhibitory concentrations to β-lactam antibiotics (except imipenem) to quinolones, such as norfloxacin and fleroxacin, chloramphenicol and tetracycline, but not to gentamicin and polymyxin B. β-Lactamase production was barely detectable in both wild-type strains and the resistant clones. Only ampicillin, cefoxitin and imipenem increased the production of β-lactamase, whereas various other β-lactams did not. Penicillin-binding proteins remained unchanged in the aztreonam-resistant clones. The analysis of the outer membrane proteins did not reveal differences in the outer membrane proteins between the wild-type strains and the aztreonam-resistant clones. Two of the three antibiotic-resistant isogenic clones contained less lipopolysaccharides (LPSs) than their corresponding wild-type strains. Moreover, it could be demonstrated that the ratio of 2-keto-3-deoxy octonate to carbohydrate of the LPS changed in any case between the wild-type strains and the aztreonam-resistant clones. These alterations were accompanied by a decrease in surface hydrophobicity of the resistant clones as compared to the wild-type strains. Therefore, quantitative as well as qualitative alterations in the LPS may provide an explanation for the resistant phenotype observed.

Characterization of a cationic surfactant-resistant mutant isolated spontaneously from Escherichia coli

“…Such multidrug resistance has been attributed mostly to either the decreased permeability of the outer membrane, in which the compositions of porin proteins and LPS are of importance, or the increased activity of efflux pumps, or both (Leying et al 1992;Nikaido 1994).…”

Mechanisms of high-level resistance to quinolones in urinary tract isolates of Pseudomonas aeruginosa

“…DISCUSSION In members of the family Enterobacteriaceae, resistance to quinolones is often due to a reduction in drug permeation associated with a decrease in OmpF, the principal porin protein (4,5,15). On the other hand, many mechanisms of resistance have been reported for P. aeruginosa (1,3,6,10,19). Yoshida et al (19) studied the proportion of gyr mutations in quinolone-resistant clinical isolates of P. aeruginosa and found that the gyrA mutation conferred various degrees of quinolone resistance on susceptible strains.…”

Isolation of Pseudomonas aeruginosa producing OXA-4 β-lactamase in a Japanese hospital in 1996

“…These antipseudomonal penam resistances may be caused by the interplay between efflux and influx proteins, and/or by qualitative and quantitative alterations in lipopolysaccharides. 7,8 The 23 piperacillin-resistant isolates were widely distributed in the hospital wards, and were made up of O-antigens A (isolation rate, 9%), B (17%), C (13%), E (53%), G (4%), and non-typable (4%). Three of the 4 isolates producing OXA-4 -lactamase, isolates 2043, 2103 and 2109, were from the urine of patients hospitalized in the urology and kidney wards, and the periods of hospitalization overlapped.…”