title: The relative frequency of intraspecific lateral gene transfer of penicillin binding proteins 1a, 2b, and 2x, in amoxicillin resistant Streptococcus pneumoniae.
abstract: Evidence exists for both interspecific and intraspecific recombination (lateral gene transfer; LGT) involving Streptococcus pneumoniae pbp (penicillin binding protein) loci. LGT of capsular genes, or serotype switching, is also know to occur between S. pneumoniae of different serotype. It is not clear whether intraspecific pbp LGT is relatively common, whether there is a difference in the relative frequency of intraspecific LGT of different pbps, and whether serotype switching is more or less frequent than pbp LGT. The purpose of this study was to use comparative evolutionary biology analysis of 216 international clinical S. pneumoniae isolates, from the Alexander Project collection, to gain insight on these issues, as well as the possible role they might be playing in spreading amoxicillin resistance. All 216 isolates were genotyped using MLST and complete or nearly complete sequences for pbp1a, pbp2b, and pbp2x were determined. Amoxicillin MICs were available for each isolate. pbps were genotyped using phylogenetics and two or more pbp types within a MLST sequence type (ST) or clonal complex were taken as putative cases of pbp LGT; these hypotheses were statistically evaluated using the approximately unbiased (AU) test. Serotypes were determined for 171 of these isolates and the minimum number of switching events necessary to explain the serotype phenotypes for each of the STs and clonal complexes were evaluated. The majority (78%) of the amoxicillin resistant isolates were comprised in 5 clonal complexes. The relative frequency of pbp LGT was greatest for pbp2b and 2x (minimum of 10.2 and 7.8%, respectively, of the isolates consistent with the LGT hypothesis), followed by 1a (3.9%). Serotype switching was more frequent than intraspecific pbp LGT (33% of isolates consistent with serotype switching hypothesis). Although intraspecific LGT of pbps is occurring and has played a role in the spread of amoxicillin resistance in S. pneumoniae, clonal dissemination appears to be more significant.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. mjs297@cornell.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stanhope
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Walsh
authors.forename: Julie A
authors.initials: JA
authors.lastname: Becker
authors.forename: Linda A
authors.initials: LA
authors.lastname: Miller
authors.forename: Tristan
authors.initials: T
authors.lastname: Lefébure
authors.forename: Ping
authors.initials: P
authors.lastname: Lang
authors.forename: Paulina D Pavinski
authors.initials: PD
authors.lastname: Bitar
authors.forename: Heather
authors.initials: H
authors.lastname: Amrine-Madsen
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D002999:Clone Cells; D024881:Drug Resistance, Bacterial; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D010802:Phylogeny; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics*
chemical_list: D046915:Penicillin-Binding Proteins; D000658:Amoxicillin