Genomic analysis and reconstruction of cefotaxime resistance in Streptococcus pneumoniae.
نویسندگان
چکیده
OBJECTIVES To identify non-penicillin-binding protein (PBP) mutations contributing to resistance to the third-generation cephalosporin cefotaxime in Streptococcus pneumoniae at the genome-wide scale. METHODS The genomes of two in vitro S. pneumoniae cefotaxime-resistant isolates and of two transformants serially transformed with the genomic DNA of cefotaxime-resistant mutants were determined by next-generation sequencing. A role in cefotaxime resistance for the mutations identified was confirmed by reconstructing resistance in a cefotaxime-susceptible background. RESULTS Analysis of the genome assemblies revealed mutations in genes coding for the PBPs 2x, 2a and 3, of which pbp2x was the only mutated gene common to all mutants. The transformation of altered PBP alleles into S. pneumoniae R6 confirmed the role of PBP mutations in cefotaxime resistance, but these were not sufficient to fully explain the levels of resistance. Thirty-one additional genes were found to be mutated in at least one of the four sequenced genomes. Non-PBP resistance determinants appeared to be mostly lineage specific. Mutations in spr1333, spr0981, spr1704 and spr1098, encoding a peptidoglycan N-acetylglucosamine deacetylase, a glycosyltransferase, an ABC transporter and a sortase, respectively, were implicated in resistance by transformation experiments and allowed the reconstruction of the full level of resistance observed in the parent resistant strains. CONCLUSIONS This whole-genome analysis coupled to functional studies has allowed the discovery of both known and novel cefotaxime resistance genes in S. pneumoniae.
منابع مشابه
Clinical Pharmacology of Cefotaxime in Neonates and Infants: Effects and Pharmacokinetics
Cefotaxime is a bactericidal "third generation" cephalosporin has a broad-spectrum activity against gram-positive microorganisms and exceptional activity against most gram-negative microorganisms. Cefotaxime is widely considered to be the antibiotic of choice for the management of neonatal meningitis and sepsis caused by gram-negative bacteria. Cefotaxime is active against Neisseria meningitis,...
متن کاملNasopharyngeal carriage, antibiotic resistance and serotype distribution of Streptococcus
Abstract Background and objectives: Colonization of nasopharynx by Streptococcus Pneumoniae can lead to pneumococcal disease. This study was performed to determine the carriage rate of nasopharyngeal S.pneumoniae in adolescents and their antibiotic susceptibility and serotype prevalence in Zahedan, Iran Material and Methods: Nasopharyngeal specimens were obtained from 865 adolescents aged 10-19...
متن کاملVery low cefotaxime concentrations select for hypermutable Streptococcus pneumoniae populations.
A mixed culture of an hypermutable hexA Streptococcus pneumoniae mutant strain and its hexA(+) isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the hexA mutant population was significantly selected at very low concentrations, and all of the tested selected variants harbored the Thr550-->Ala mutation in pbp2x. Since cefotaxime selec...
متن کاملAntimicrobial susceptibility and analysis of macrolide resistance genes in Streptococcus pneumoniae isolated in Hamadan
Objective(s): Macrolide resistant Streptococcus pneumoniae pose an emerging problem globally. The aim of this study was to investigate the prevalence of ermB and mefA genes (macrolide resistant genes) by polymerase chain reaction (PCR) method and to detect drug resistance patterns of S. pneumoniae isolated from clinical samples to macrolides and other antibiotic agents by E-test method. Materia...
متن کاملMultidrug Resistance in Infants and Children
Bacterial infections may cause disease and death. Infants and children are often subject to bacterial infections. Antimicrobials kill bacteria protecting the infected patients andreducing the risk of morbidity and mortality caused by bacteria. The antibiotics may lose their antibacterial activity when they become resistant to a bacteria. The resistance to different antibiotics in a bacteria is ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of antimicrobial chemotherapy
دوره 68 8 شماره
صفحات -
تاریخ انتشار 2013