Limited adaptive evolution ofStaphylococcus aureusduring transition from colonization to invasive infection

Abstract

Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified and phenotypic traits are understudied. We therefore assessed pheno- and genotypic profiles of eleven S. aureus isolate pairs sampled from colonized patients simultaneously suffering from invasive S. aureus infections. Ten out of 11 isolate pairs presented the same spa and MLST suggesting colonization as origin for the invasive infection. Systematic analysis of colonizing and invasive isolate pairs showed similar adherence, hemolysis and reproductive fitness properties, minimal genetic differences, identical antibiotic tolerance and bacterial virulence in Galleria mellonella. Our results provide insights into the similar phenotype associated with limited adaptive genetic evolution between the colonizing and invasive isolates. Disruption of the physical barriers mucosa or skin were identified in the majority of patients further emphasizing colonization as a major risk factor for invasive disease.

Group AStreptococcusstrains causing meningitis without distinct invasive phenotype

“…On the pathogen’s side, no common features explaining bacterial spread to the brain were found among the meningitis isolates. This points to host rather than pathogen factors playing a role in facilitating bacterial invasion, as previously described for S. aureus [11]. Adherence and invasion assays towards HBMECs confirmed the absence of a particular tropism towards brain microvascular tissue for the meningitis isolates, excluding an advantage in crossing or damaging the blood brain barrier for these isolates, as compared to otitis and colonizing ones, in the tested settings.…”

“…On the pathogen's side, no common features explaining bacterial spread to the brain were found among the meningitis isolates. This points to host rather than pathogen factors playing a role in facilitating bacterial invasion, as previously described for S. aureus [11].…”

“…Whole genome sequencing and genomic data analysis were performed as previously described [11]. Briefly, from 150 bp paired end reads, de novo assemblies were generated with SPAdes v.3.10[11] and annotated with Prokka v.1.13 [12].…”

“…Whole genome sequencing and genomic data analysis were performed as previously described [11]. Briefly, from 150 bp paired end reads, de novo assemblies were generated with SPAdes v.3.10[11] and annotated with Prokka v.1.13 [12]. A pangenome was constructed with Roary v.3.12 [13] and the resulting core-gene alignment was used to build a maximum likelihood phylogenetic tree with Fasttree v.2.1.10 [14].…”

Group AStreptococcusantibiotic tolerance in necrotizing fasciitis

“…Genotypic characterization of the clinical isolates included typing of the emm gene, encoding the surface M-protein, and of the covS gene, involved in virulence factors expression regulation. Typing of the emm and covS genes was performed in silico, based on the whole-genome of the five GAS strains sequenced, assembled and annotated as previously described [12]. In brief, GAS strains were whole-genome sequenced on a MiSeq instrument.…”