APPLICATIONS OF PYROLYSIS MASS-SPECTROMETRY IN STUDIES ON THE MODE OFACTION OF ANTIMICROBIAL AGENTS

Changes in overall cell composition during exposure to antimicrobial a gents were investigated by pyrolysis mass spectrometry (Py-MS) in pare ntal (O-K+), K antigen deficient (O+K-), and O and K antigen deficient (O-K-) strains of Klebsiella aerogenes NCTC 5055. Changes followed di stinct patterns thar correlated with mode of action: penicillin bindin g protein (PBP) 3 blockade (ceftazidime, piperacillin); PBP 2 blockade (imipenem); membrane disruption (colistin); bacteriostatic (chloramph enicol), and bactericidal (gentamicin) protein synthesis inhibition; a nd DNA synthesis inhibition (ciprofloxacin). Changes were pronounced a fter exposure for 1 hour at 10 x MIC. In general, the O-K- strain show ed the largest compositional shifts, and the parental O+K+ strain the least shifts, correlating with bactericidal kinetic studies. Py-MS may be useful in studies of the mode of action of antimicrobial agents, p articularly in early screening of new compounds, and in rapid detectio n of the effects of antimicrobial agents on micro-organisms.