Release of exotoxin A, peptidoglycan and endotoxin after exposure of clinical Pseudomonas aeruginosa isolates to carbapenems in vitro.
BACKGROUND
Production of several cell-associated components and extracellular enzymes can play important roles in the pathogenesis of Pseudomonas aeruginosa infections.


METHODS
We characterized the time course of morphological changes, production of exotoxin A (ETA) and release of peptidoglycan (PG) and endotoxin (ET) in clinical P. aeruginosa isolates after exposure to carbapenems including imipenem, panipenem, meropenem and biapenem at 0.5, 2, 8 and 32 microg/ml.


RESULTS
The amount of ETA in the supernatant of bacterial cultures exposed to carbapenems correlated with the number of viable cells, independently of morphological changes. Formation of ovoid cells and rapid cell lysis induced by carbapenems above the minimal inhibitory concentrations (MICs) decreased ETA production and ET release, while filamentation and prolonged cell lysis increased ETA production and/or ET release. Neither the number of viable cells nor bacterial morphology was related to the amount of PG released throughout the 6-hour observation period.


CONCLUSIONS
Exposure to concentrations of carbapenems above the MIC resulted in rapid cell lysis of P. aeruginosa and decreased ETA levels and ET release, while filamentation and prolonged cell lysis induced by exposure to sub-MICs of carbapenems were associated with increased ETA production and/or greater ET release.
Horii
Toshinobu
T
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan. horiihm@hama-med.ac.jp
Muramatsu
Hideaki
H
Monji
Akio
A
Miyagishima
Daisuke
D
D036002:ADP Ribose Transferases / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000378:metabolism*; D005098:Exotoxins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D037521:Virulence Factors / Q000378:metabolism*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D015780:Carbapenems; D004731:Endotoxins; D005098:Exotoxins; D010457:Peptidoglycan; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A