[Gentamicin-induced alteration in drug susceptibility and lipopolysaccharide-composition of Pseudomonas aeruginosa isolates].
Emergency of multi-drug resistance in Pseudomonas aeruginosa isolates after exposure to gentamicin was investigated with reference to their LPS-compositions. Three strains each of P. aeruginosa, different in LPS-compositions (long- and short-LPS strains, and LPS-deficient strain) were once or repeatedly incubated overnight at 35 degrees C in Mueller-Hinton broth including different concentrations of gentamicin, a poly-cationic antibiotic. LPS-compositions of the bacteria which survived and were grown after exposure to gentamicin were analyzed and the susceptibility to some of anti-pseudomonal drugs was determined. Of the test 9 strains after single exposure, No. 4 (long-LPS) and No. 41 (short-LPS) formed the LPS-deficient mutants. The resistance to ceftazidime and gentamicin was found in No. 4 strain, but not in No. 41 strain. Drug resistance in different patterns was also found in Nos. 43, 29, 45 and 52 strains without any change in their LPS-compositions. Contrary to these results, the susceptibility to norflxacin increased in Nos. 21 and 45 strains without any change in their LPS-compositions. After repeated exposures to gentamicin, the LPS-compositions of Nos. 4 and 14 (short-LPS) were altered and formed the LPS-deficient and the Intermediate-LPS (between short and long compositions) mutants, respectively. The LPS-alteration in both strains were accompanied by the development of resistance to ceftazidime and gentamicin, respectively. The drug resistance in different patterns were also found in Nos. 43, 156, 29, 41, 21, 45 and 52 strains, without any change in the LPS-compositions, whereas the increase in susceptibility to norfloxacin was simultaneously found in No. 45 strain. The ionic-binding of [3H]-gentamicin to the cell surfaces of two LPS-deficient mutants of P. aeruginosa decreased markedly, in comparison with that of the respective parents, and these results might lead to the drug resistance in the LPS-deficient mutants. However, the gentamicin-induced resistance of some strains of P. aeruginosa (but no change in the LPS-compositions) to the test drugs including gentamicin indicates a possibility that negative charges on the bacterial surface were decreased by the drug exposure. The drug resistance and LPS-compositions in the gentamicin-induced mutants of P. aeruginosa were stable during or after the 15th in vitro serial transfers.
Hasegawa
M
M
Chemotherapy Division, Mitsubishi Kagaku Bio Clinical Laboratories, Inc.
Kobayashi
I
I
Saika
T
T
Nishida
M
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005839:Gentamicins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008070:Lipopolysaccharides