Contents lists available at ScienceDirect International Journal of Medical Microbiology journal homepage: www.elsevier.com/locate/ijmm Short communication The invasive MenC cc103 lineage with penicillin reduced susceptibility persisting in Brazil Érica L. Fonseca a, ⁎ , Michel A. Marin a , Fernanda S. Freitas a , Bruna S.A. Vitório b , Flávio M.G. de Araújo c , Dhian R.A. Camargo d , Roney S. Coimbra e , Ivano R. De Filippis b , Ana Carolina P. Vicente a a Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil b Instituto Nacional de Controle de Qualidade em Saúde - INCQS, FIOCRUZ, Rio de Janeiro, RJ, Brazil c Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brazil d Informática de Biossistemas, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil e Neuromgenômica, Centro de Pesquisa René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil ARTICLE INFO Keywords: Altered penA Penicillin reduced susceptibility ST-103 clonal complex Fitness Neisseria meningitidis 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 de- termined 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. 1. Introduction Neisseria meningitidis may asymptomatically colonize the upper human respiratory tract, and occasionally cause meningitis and septi- caemia (Rosenstein et al., 2001), which are associated with significant morbidity and mortality worldwide. The most invasive meningococci belong to the serogroups A, B, C, W and Y (Harrison et al., 2013). The serogroup C (MenC) from clonal complex 103 (cc103) is currently the most prevalent serogroup in Brazil, accounting for ∼40% of invasive disease (Bastos et al., 2015; Ibarz-Pavón et al., 2012; Sáfadi et al., 2013). Penicillin is the first-line drug for treating meningococcal infection (Nadel and Kroll, 2007), and it targets the penicillin-binding protein 2 (PBP2), encoded by penA, that participates in peptidoglycan biosynth- esis during cell wall formation. However, the growing worldwide emergence of strains presenting penicillin reduced susceptibility (pen I ) has been reported. Such phenotype is associated with five specific amino acid polymorphisms in the transpeptidase region of PBP2 C- termini (Antignac et al., 2001; Taha et al., 2007; Thulin et al., 2006). In Brazil, the meningococcal disease is endemic and ∼1600 con- firmed cases had been reported in 2014. As found worldwide, strains with reduced susceptibility to penicillin have also increased in Brazil, and recent studies showed that ∼14% of invasive N. meningitidis pre- sented penicillin MICs ranging from 0.064–0.5 mg/L, which is asso- ciated with the pen I phenotype (Gorla et al., 2011; Ibarz-Pavón et al., 2012). However, the diversity of penA circulating in the country and its association with pen I phenotype was not assessed yet. Here, we aimed to determine the scenario of penA diversity, their association with resistance and distribution among prevalent invasive meningococci serogroups in Brazil. http://dx.doi.org/10.1016/j.ijmm.2017.05.004 Received 31 January 2017; Received in revised form 24 April 2017; Accepted 21 May 2017 ⁎ Corresponding author at: Laboratório de Genética Molecular de Microrganismos, Instituto Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, CEP 21040-360, Brazil. E-mail address: ericafon@ioc.fiocruz.br (É.L. Fonseca). International Journal of Medical Microbiology xxx (xxxx) xxx–xxx 1438-4221/ © 2017 Elsevier GmbH. All rights reserved. Please cite this article as: Fonseca, É.L., International Journal of Medical Microbiology (2017), http://dx.doi.org/10.1016/j.ijmm.2017.05.004