title: Applications of pyrolysis mass spectrometry in studies on the mode of action of antimicrobial agents.
abstract: Changes in overall cell composition during exposure to antimicrobial agents were investigated by pyrolysis mass spectrometry (Py-MS) in parental (O+K+), K antigen deficient (O+K-), and O and K antigen deficient (O-K-) strains of Klebsiella aerogenes NCTC 5055. Changes followed distinct patterns that correlated with mode of action: penicillin binding protein (PBP) 3 blockade (ceftazidime, piperacillin); PBP 2 blockade (imipenem); membrane disruption (colistin); bacteriostatic (chloramphenicol), and bactericidal (gentamicin) protein synthesis inhibition; and DNA synthesis inhibition (ciprofloxacin). Changes were pronounced after exposure for 1 hour at 10 x MIC. In general, the O-K- strain showed 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, particularly in early screening of new compounds, and in rapid detection of the effects of antimicrobial agents on micro-organisms.
authors.affiliation: Department of Microbiology, Children's Hospital, Sheffield, UK.
authors.forename: J T
authors.initials: JT
authors.lastname: Magee
authors.forename: J M
authors.initials: JM
authors.lastname: Hindmarch
authors.forename: T G
authors.initials: TG
authors.lastname: Winstanley
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D013058:Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents