Genomic Analyses of Clonal Isolates Provide Clues to the Evolution of Streptococcus pneumoniae

Organization, 2003). Efforts to limit pneumococcal disease have focused primarily on antibiotic intervention and vaccination. However, after initial, and often dramatic, successes the effectiveness of these measures has consistently been overcome by the extremely adaptable and resilient pneumococcus. S. pneumoniae is naturally competent and readily incorporates DNA fragments derived from pneumococcal and non-pneumococcal bacterial species into its genome by homologous recombination. High levels of recombination have resulted in extreme diversity within pneumococcal populations from which variant genotypes can rapidly emerge in the presence of changing selective pressures. The primary pressures outside of natural immunity are antibiotics and pneumococcal conjugate polysaccharide vaccines. Resistant and multidrug resistant pneumococci have emerged since the late 1960s and now severely limit treatment options for pneumococcal diseases (Reinert, 2009). The incidences of invasive pneumococcal disease (IPD) and antibiotic resistant pneumococci decreased dramatically following the introduction of the heptavalent conjugate vaccine PCV7 in 2000 (Dagan, 2009). However, the incidence of IPD and resistance is again rising due to the emergence of multidrug resistant, non-vaccine “replacement” serotypes. Croucher et al. (2011) documented the “escape” of the PMEN1 clone from PCV7 by indentifying several independent horizontal transfer events that resulted in serotype switching of PMEN1 strains from vaccine serotype 23F to non-vaccine serotypes. This suggested strong selective pressures for capsule switch variants exerted by the PCV7-immunized human immune system. Evidence for the selective pressures exerted by antibiotics was also reported. Analysis of integrative and conA commentary on