Extensive Horizontal Gene Transfer during Staphylococcus aureus Co-colonization In Vivo

Abstract

Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests that colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance, and immune evasion pathways. Antimicrobial-resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex 398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGE from the pig to the human isolate was detected within 4 h. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGE. Staphylococcus aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonization, clones coexisted and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that horizontal gene transfer occurs at very high frequency in vivo and significantly higher than that detectable in vitro.

Resistance to the tetracyclines and macrolide-lincosamide-streptogramin group of antibiotics and its genetic linkage – a review

“…Transfer of antimicrobial resistance, however, is highly influenced by the complexity of microflora and its interactions with the host. Moreover, it is presumed that in vitro models underestimate the potential risk for resistance transfer compared to in vivo models [58,59]. Therefore, to appropriately assess the risk for horizontal spread of antimicrobial resistance, many authors have recently performed experimental studies under in vivo conditions.…”

The Plasmidome of Firmicutes: Impact on the Emergence and the Spread of Resistance to Antimicrobials

“…Such selective processes favor the emergence of novel variants, resulting from genetic drift, or migration to heterogeneous environments. Recent studies demonstrated that plasmid transfer occurs in vivo more frequently than in experimental evolution assays (43), and that gradients in populations under selection pressure by diverse antimicrobials favor selection of multidrug resistance (MDR) plasmids (44,45).…”

Transposase-Mediated Excision, Conjugative Transfer, and Diversity of ICE 6013 Elements in Staphylococcus aureus

“…1B). Besides the potential for programmed ribosomal frameshifting (38) by the 3= poly(A) 5 tract, the two 5= poly(A) 7 tracts occur directly after the initiation codon of orf2 and may add another layer of control over ICE6013 excision.…”

“…transducing phages and conjugative plasmids in the horizontal transfer of antimicrobial resistance determinants and virulence factors continue to be documented (3)(4)(5)(6)(7), but little is known about the function of integrative conjugative elements (ICEs) in this species. ICEs, also known as conjugative transposons (Tn's), are maintained primarily by integration into a bacterial chromosome or plasmid and are horizontally transferred by self-encoded conjugation functions (8).…”