Inhibition of Pseudomonas aeruginosa exoenzyme expression by subinhibitory antibiotic concentrations.
We examined the effects of subinhibitory concentrations of ciprofloxacin, tobramycin, and ceftazidime on Pseudomonas aeruginosa exoenzyme expression in vitro and in vivo. Exotoxin A, exoenzyme S, phospholipase C, elastase, and total protease activities were suppressed by antibiotics at concentrations as low as 1/20 of the MIC over a 24-h period in broth. Continuous 10-day exposure of P. aeruginosa DG1 broth cultures to antibiotic levels equal to 1/10 of the MIC reduced exoenzyme S activity in all treatment groups. Elastase activity was reduced only by ciprofloxacin and tobramycin treatment. This suppressive effect of the antibiotics persisted throughout the 10 days and was not influenced by the increase in MIC of ciprofloxacin detected during the course of the experiment. Rats chronically infected with P. aeruginosa were treated with subinhibitory doses of antibiotics and compared with untreated controls. Bacterial numbers in lung homogenates from each of the four study groups were identical. However, the lungs from antibiotic-treated rats had significantly less histological damage than those from control rats (P less than 0.001). The protective effect was greatest for ciprofloxacin and tobramycin. Further, P. aeruginosa isolates from ciprofloxacin- and tobramycin-treated rats demonstrated significantly less exoenzyme S and elastase activity than isolates from untreated rats (P less than 0.001). Isolates from ceftazidime-treated lungs expressed less exoenzyme S activity (P less than 0.001) but an equivalent amount of elastase activity as isolates from controls. The suppression of P. aeruginosa exoenzymes may arrest progressive lung injury during chronic P. aeruginosa lung infections.
Grimwood
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Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences-Centre, Alberta, Canada.
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D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D002442:Ceftazidime / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000037:antagonists & inhibitors; D008168:Lung / Q000473:pathology; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014031:Tobramycin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002442:Ceftazidime; D002939:Ciprofloxacin; D005098:Exotoxins; D010196:Pancreatic Elastase; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011480:Protease Inhibitors; D014031:Tobramycin; D010738:Type C Phospholipases; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C444820:exoenzyme S