Abstract

BackgroundStreptococcus pneumoniae, also called the pneumococcus, is a major bacterial pathogen. Since its introduction in the 1940s, penicillin has been the primary treatment for pneumococcal diseases. Penicillin resistance rapidly increased among pneumococci over the past 30 years, and one particular multidrug-resistant clone, PMEN1, became highly prevalent globally. We studied a collection of 426 pneumococci isolated between 1937 and 2007 to better understand the evolution of penicillin resistance within this species.ResultsWe discovered that one of the earliest known penicillin-nonsusceptible pneumococci, recovered in 1967 from Australia, was the likely ancestor of PMEN1, since approximately 95% of coding sequences identified within its genome were highly similar to those of PMEN1. The regions of the PMEN1 genome that differed from the ancestor contained genes associated with antibiotic resistance, transmission and virulence. We also revealed that PMEN1 was uniquely promiscuous with its DNA, donating penicillin-resistance genes and sometimes many other genes associated with antibiotic resistance, virulence and cell adherence to many genotypically diverse pneumococci. In particular, we describe two strains in which up to 10% of the PMEN1 genome was acquired in multiple fragments, some as long as 32 kb, distributed around the recipient genomes. This type of directional genetic promiscuity from a single clone to numerous unrelated clones has, to our knowledge, never before been described.ConclusionsThese findings suggest that PMEN1 is a paradigm of genetic success both through its epidemiology and promiscuity. These findings also challenge the existing views about horizontal gene transfer among pneumococci.

Highlights

  • Streptococcus pneumoniae, called the pneumococcus, is a major bacterial pathogen

  • This selective pressure meant that pneumococci with some level of resistance to penicillin or other antibiotics had a distinct advantage over susceptible strains, which may have indirectly contributed to a change in the distribution of pneumococcal capsular types [11]

  • PMEN1 pbp promiscuity Pneumococcal study isolates (Table 1) were assigned to clonal complex (CC) based on multilocus sequence type (MLST) data

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Summary

Introduction

Streptococcus pneumoniae, called the pneumococcus, is a major bacterial pathogen. Over 1.6 million deaths annually are attributed to the bacterial pathogen Streptococcus pneumoniae, the ‘pneumococcus’ [1] This bacterium is a leading cause of otitis media, sinusitis, pneumonia and meningitis, and is associated with high mortality rates in the developing world [1,2]. The selective pressure of antibiotic use was enormous at this time, as antibiotics were widely used, even overused, in many countries This selective pressure meant that pneumococci with some level of resistance to penicillin or other antibiotics had a distinct advantage over susceptible strains, which may have indirectly contributed to a change in the distribution of pneumococcal capsular types (or serotypes, defined by the antigenic polysaccharide capsule surrounding the cell) [11]. There has been an increase in pneumococcal disease due to non-PCV7 type pneumococci [13], many of which are penicillin nonsusceptible [14]. 10- and 13-valent pneumococcal vaccines, containing additional serotypes, have recently been introduced, and continued surveillance over the few years will be essential to determine their effects

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