title: Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible.
abstract: It has recently been reported that penicillin-sensitive pneumococci may exhibit reduced susceptibility to oxacillin, resulting in their misclassification as being penicillin resistant by oxacillin disk testing. Intermediate oxacillin resistance (MIC, 1.0 microgram/ml) in three of these apparently unrelated penicillin-susceptible clinical isolates of Streptococcus pneumoniae isolated in the United Kingdom and in four Spanish isolates was shown to be solely due to the acquisition of a gene encoding an altered penicillin-binding protein (PBP), PBP2X. PBP2X genes cloned from typical penicillin-resistant isolates of S. pneumoniae that possessed high-level oxacillin resistance were shown to be able to transform susceptible isolates of S. pneumoniae to intermediate oxacillin resistance. In all instances, the intermediately oxacillin-resistant PBP2X transformants retained susceptibility to penicillin (MIC, 0.06 microgram/ml). Under appropriate selective pressure, the acquisition of a low-affinity PBP2X by penicillin-susceptible pneumococci could result in an increasing number of false positives for penicillin resistance among isolates of S. pneumoniae screened with oxacillin. Additionally, these intermediately oxacillin-resistant isolates showed reduced susceptibility to cefotaxime, an agent likely to be prescribed in place of penicillin for the treatment of serious infections due to these apparently penicillin-resistant organisms.
authors.affiliation: Microbial Genetics Group, School of Biological Sciences, University of Sussex, Falmer, Brighton, United Kingdom.
authors.forename: C G
authors.initials: CG
authors.lastname: Dowson
authors.forename: A P
authors.initials: AP
authors.lastname: Johnson
authors.forename: E
authors.initials: E
authors.lastname: Cercenado
authors.forename: R C
authors.initials: RC
authors.lastname: George
mesh_terms: D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D006602:Hexosyltransferases; D006801:Humans; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D010068:Oxacillin / Q000494:pharmacology*; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010458:Peptidyl Transferases; D011008:Pneumococcal Infections / Q000382:microbiology; D013030:Spain; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010068:Oxacillin