Abstract
A mutant with decreased susceptibility to imipenem (IpR) was selected in vitro from a susceptible clinical isolate of Listeria monocytogenes (IpS). IpR exhibited decreased susceptibility to penicillin G (4 x MIC) and imipenem (16 x MIC) and increased susceptibility to cefotaxime (0.25 x MIC). Electrophoretic profiles of membrane proteins and penicillin-binding proteins (PBPs) were identical in the two strains; each strain had five PBPs with molecular masses of ca. 97, 83.3, 81, 77.1, and 42.6 kilodaltons. A decreased affinity of PBP 3 for penicillin G and imipenem (10-fold) was observed in IpR. In contrast, the affinity of PBP 3 for cefotaxime in IpR was increased twofold and correlated with the decreased MIC of this drug. From these findings and competition experiments with different beta-lactam antibiotics, we conclude that the alteration of PBP 3 is responsible for the decreased susceptibility of IpR to penicillin and imipenem and that PBP 3 might be an essential target of beta-lactam antibiotics in L. monocytogenes.
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- Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
- Brown D. F., Reynolds P. E. Intrinsic resistance to beta-lactam antibiotics in Staphylococcus aureus. FEBS Lett. 1980 Dec 29;122(2):275–278. doi: 10.1016/0014-5793(80)80455-8. [DOI] [PubMed] [Google Scholar]
- Chambers H. F. Coagulase-negative staphylococci resistant to beta-lactam antibiotics in vivo produce penicillin-binding protein 2a. Antimicrob Agents Chemother. 1987 Dec;31(12):1919–1924. doi: 10.1128/aac.31.12.1919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gaillard J. L., Berche P., Sansonetti P. Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun. 1986 Apr;52(1):50–55. doi: 10.1128/iai.52.1.50-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutmann L., Williamson R., Tomasz A. Physiological properties of penicillin-binding proteins in group A streptococci. Antimicrob Agents Chemother. 1981 May;19(5):872–880. doi: 10.1128/aac.19.5.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moellering R. C., Jr, Medoff G., Leech I., Wennersten C., Kunz L. J. Antibiotic synergism against Listeria monocytogenes. Antimicrob Agents Chemother. 1972 Jan;1(1):30–34. doi: 10.1128/aac.1.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traub W. H. Perinatal listeriosis. Tolerance of a clinical isolate of Listeria monocytogenes for ampicillin and resistance against cefotaxime. Chemotherapy. 1981;27(6):423–431. doi: 10.1159/000238012. [DOI] [PubMed] [Google Scholar]
- Vicente M. F., Pérez-Dáz J. C., Baquero F., Angel de Pedro M., Berenguer J. Penicillin-binding protein 3 of Listeria monocytogenes as the primary lethal target for beta-lactams. Antimicrob Agents Chemother. 1990 Apr;34(4):539–542. doi: 10.1128/aac.34.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]