Evolution of the β-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain

Abstract

Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.

Two multi-fragment recombination events resulted in the β-lactam-resistant serotype 11A-ST6521 related to Spain9V-ST156 pneumococcal clone spreading in south-western Europe, 2008 to 2016

“…A common PBP1A allele (allele 15) identical to that of PMEN1 (American Type Culture Collection 700669) was shared by all but three isolates (the latter presented allele 7 and a new allele (NEW1) close to allele 96 (96% identity)). We found the changes at the STMK373 motif (T371A allele 15 and T371S in allele NEW1) that had been previously described [15]…”

“…Two additional 11A lineages (ST156 and ST166) were identified among French, Italian and Portuguese isolates. However, the β-lactam MIC were lower than those of ST838 and ST6521, in which high amoxicillin MIC are related to amino acid changes in the transpeptidase domain of PBP2B (residues 590-641), as described [15].…”

“…In fact, most of serotype 14 isolates causing IPD in the pre-PCV era were related to the PMEN3 recombinant lineage [13,14]. Besides serotype 14, PMEN3 recombined with other serotypes showing a high capacity to exchange the capsular locus, resulting in the evasion of the vaccine effects [15].…”

Lysogeny in Streptococcus pneumoniae

“…The presence of more than one prophage per genome, or polylysogeny, has been reported in various studies, and appears to be a relatively frequent feature of S. pneumoniae [ 20 , 38 , 52 , 65 ]. A detailed comparison of phages found in polylysogenic isolates has not been performed, however, it appears to occur with phages that belong to distinct phylogenetic groups and with distinct integration sites [ 20 , 38 , 52 , 65 ]. This might reflect inability of phages to integrate in tandem in the same attB site, or the activation of phage superinfection resistance mechanisms.…”

“…Despite the easy and relatively cheap access to whole-genome sequencing, assembly of sequencing data is confounded by the nature of pneumococcal phages themselves, such as the presence of repeated domains within the pblB variants encoded by many phages and homology with chromosomal genes such as between the host lytA gene and phage lytic amidases [ 20 , 48 , 49 , 65 ]. Mobile genetic elements (MGEs) are notorious for creating genome assembly problems, with contigs often ending within MGE sequences [ 69 ].…”