The invasive MenC cc103 lineage with penicillin reduced susceptibility persisting in Brazil

Abstract

Penicillin is the antibiotic of choice for the treatment of meningococcal infections, and mutations in penA gene are involved with reduced susceptibility (pen^I) emergence to this antibiotic. This study aimed to characterize the penA allelic diversity, their association with pen^I phenotype and distribution among prevalent meningococci serogroups in Brazil. The entire penA from 49 invasive strains of distinct serogroups circulating in Brazil for more than two decades were obtained by PCR and sequencing. Additionally, the penA from 22 publicly available complete Neisseria meningitidis genomes from Brazil were included in the study. The allelic diversity was determined and a genetic tree was built using the penA sequence alignment. The penicillin MIC was obtained by the E-Test method. In general, the identified penA alleles correlated with the observed pen^I phenotype. The canonical penA1 was the most prevalent allele, however, several altered penA were also identified in strains presenting increased penicillin MICs. It was identified a new penA amino acid position (residue 480) that possibly influence the penicillin MIC in some strains. Interestingly, the altered penA14 was found in pen^I invasive MenC cc103 strains spread in Brazil and persisting since 2011, indicating that the biological cost imposed by pen^I phenotype can be ameliorated by particular features present in this lineage, which represents an additional public health threat.

Keywords: Altered penA; Fitness; Neisseria meningitidis; Penicillin reduced susceptibility; ST-103 clonal complex.