Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis

Akuzike Kalizang'Oma,Stephen D Bentley,Robert S Heyderman,Bernard Beall,Andrea Gori,David Goldblatt,Martin Antonio,Sandra Beleza,Brenda Kwambana-Adams,Chrispin Chaguza,Charlotte Davison

doi:10.1099/mgen.0.000622

Abstract

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus , the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis , Streptococcus oralis and S. pneumoniae . With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis . Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced β-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis .

Highlights

Streptococcus pneumoniae is a common nasopharyngeal commensal among children and HIV-a ffected adult populations in sub-S aharan Africa [1, 2]
We demonstrate extensive horizontal genetic transfer (HGT) among the pbp genes of frequently carried pneumococcal serotypes and Global Pneumococcal Sequence Clusters (GPSCs) associated with long carriage duration, high recombination rates and reduced β-lactam susceptibility
Together these data indicate that the S. mitis are an important reservoir of pbp genetic diversity that may facilitate the acquisition of antimicrobial resistance (AMR), amongst commonly carried pneumococcal vaccine serotype (VT) and non-vaccine serotypes (NVTs) associated with expanding and emerging pneumococcal lineages

Summary

Introduction

Streptococcus pneumoniae is a common nasopharyngeal commensal among children and HIV-a ffected adult populations in sub-S aharan Africa (sSA) [1, 2]. In the United States the post-PCV introduction era has seen the expansion of serotype 35B sequence type (ST) 558 [17], a resistant NVT lineage that has been associated with IPD in the region, as well as a 35B switch variant that has recently emerged [8, 17, 18]. In high disease burden regions, immunised children continue to carry antibiotic resistant VTs, which include serotypes 19A and 19F, despite good vaccine coverage [11, 19,20,21]. Multidrug- resistant (MDR) S. pneumoniae clones defined by the Pneumococcal Molecular Epidemiology Network (PMEN) [22], such as Sweden15A-25/ST63 and Netherlands15B-37/ST199, spreading globally continue to remain important causes of invasive disease in the post-PCV13 era [23,24,25]

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Results

Conclusion