Comprehensive identification of single nucleotide polymorphisms associated with Beta-lactam resistance within pneumococcal mosaic genes

Streptococcus pneumoniae is carried asymptomatically in the nasopharyngeal tract. However, it is capable of causing multiple diseases, including pneumonia, bacteraemia and meningitis, which are common causes of morbidity and mortality in young children. Antibiotic treatment has become more difficult, especially that involving the group of beta-lactam antibiotics where resistance has developed rapidly. The organism is known to be highly recombinogenic, and this allows variants conferring beta-lactam resistance to be readily introduced into the genome. Identification of the specific genetic determinants of beta-lactam resistance is essential to understand both the mechanism of resistance and the spread of resistant variants in the pneumococcal population. Here, we performed a genome-wide association study on 3,701 isolates collected from two different locations and identified candidate variants that may explain beta-lactam resistance as well as discriminating potential genetic hitchhiking variants from potential causative variants. We report 51 loci, containing 301 SNPs, that are associated with beta-lactam non-susceptibility. 71 out of 301 polymorphic changes result in amino acid alterations, 28 of which have been reported previously. Understanding the determinants of resistance at the single nucleotide level will be important for the future use of sequence data to predict resistance in the clinical setting.

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