A spontaneous mutant of Neisseria gonorrhoeae with decreased resistance to neutrophil granule proteins.
We examined the resistance of Neisseria gonorrhoeae to proteins prepared from the granules of human polymorphonuclear neutrophils (PMNs). We found that nearly isogenic strains differing in lipopolysaccharide subunit molecular weight also differed in levels of resistance to crude granule extracts. N. gonorrhoeae strain WS1 was at least 10-fold less resistant than the parental strain FA 102 to granule extracts. Surprisingly, strain WS1 did not differ from FA 102 in resistance to two isolated antimicrobial proteins obtained previously from extracts of human PMN granules. We used strain WS1 in assays that detected antimicrobial proteins in granule extracts, and we obtained at least two proteins with apparent molecular masses of 24-25.5 kilodaltons that exerted potent in vitro antigonococcal activity. We found that the ED50 (concentration of protein required to kill 50% of gonococci) against the strain WS1 was approximately 0.006 microgram of protein/ml, whereas the ED50 against the parental strain (FA 102) was approximately 0.4 microgram of protein/ml. Accordingly, alterations in lipopolysaccharide structure apparently caused a 66-fold decrease in gonococcal resistance to granule proteins. Our data suggest that gonococcal resistance to oxygen-independent antimicrobial systems of human PMNs may, in part, depend on the availability of certain lipopolysaccharide domains involved in recognition of the antimicrobial granule proteins described in this report.
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D006801:Humans; D008070:Lipopolysaccharides / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics; D012697:Serine Endopeptidases
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; C030509:neutrophil basic proteins; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G