title: Altered PBP 2A and its role in the development of penicillin, cefotaxime, and ceftriaxone resistance in a clinical isolate of Streptococcus pneumoniae.
abstract: We report the unusual involvement of altered PBP 2A in the development of beta-lactam resistance in Streptococcus pneumoniae. This was investigated amid three identical serotype 14 isolates (designated isolates 1, 2, and 3, respectively) of pneumococci cultured successfully from the blood of a human immunodeficiency virus-seropositive child with recurrent pneumonia. The passage of this strain through its human host induced several changes in the bacterium, which is typical of the adaptive and evolving nature of the pneumococcus. An efflux resistance mechanism, which conferred increased ciprofloxacin resistance, was induced in isolates 2 and 3. In addition, faster growth rates and larger capsules were also observed for these isolates, with respect to isolate 1. Notably, compared to isolates 1 and 2, isolate 3 showed a decrease in penicillin, cefotaxime, and ceftriaxone resistance. This change was associated with the replacement of an altered PBP 2A for an unaltered PBP 2A. In all likelihood, these events produced a strain which evolved into a fitter and more virulent type, isolate 3, that resulted in an aggravated pneumococcal infection and ultimately in the patient's death.
authors.affiliation: MRC/NICD/WITS Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, P.O. Box 1038, Johannesburg 2000, South Africa. anthony.smith@nhls.ac.za
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Smith
authors.forename: Charles
authors.initials: C
authors.lastname: Feldman
authors.forename: Orietta
authors.initials: O
authors.lastname: Massidda
authors.forename: Kerrigan
authors.initials: K
authors.lastname: McCarthy
authors.forename: Dalu
authors.initials: D
authors.lastname: Ndiweni
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
mesh_terms: D002439:Cefotaxime / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D018550:Cephalosporin Resistance / Q000502:physiology*; D002648:Child; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005838:Genotype; D006679:HIV Seropositivity / Q000382:microbiology; D006801:Humans; D008858:Microscopy, Phase-Contrast; D008969:Molecular Sequence Data; D010403:Penicillin Resistance / Q000502:physiology*; D046915:Penicillin-Binding Proteins / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development; D014170:Transformation, Genetic
chemical_list: D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; C478699:penicillin-binding protein 2a, Streptococcus; D002443:Ceftriaxone; D010453:Peptide Synthases; D002439:Cefotaxime