NEW YORK (GenomeWeb) – An international team led by investigators at the University of Edinburgh has shown that pathogenic Staphylococcus aureus strains likely gain the ability to bounce between host species by swapping host-specific mobile genetic elements and other sequences.
The researchers traced S. aureus features coinciding with the bug's host range, using population sequence data for 800 isolates collected from dozens of hosts species across five continents. Their results, published online yesterday in Nature Ecology & Evolution, implicated humans as a "major hub" at the center of S. aureus host jumps and highlighted the exchange of genetic elements by horizontal transfer as such host switching occurs.
"Our findings provide a framework to understand how some bacteria can cause disease in both humans and animals and could ultimately reveal novel therapeutic targets," senior author Ross Fitzgerald, a researcher at the University of Edinburgh's Roslin Institute and director of Edinburgh Infectious Diseases, said in a statement.
"The data reveal the impact of human activities such as domestication and the use of antibiotics in medicine and agriculture on the recent evolution of S. aureus, and identify the key evolutionary processes underpinning its multi-host-species ecology," he and his co-authors wrote.
While many S. aureus strains are non-pathogenic, others can cause serious infections in humans, livestock, chickens, and other animals. In particular, methicillin-resistant S. aureus (MRSA) has been implicated in serious hospital- or community-acquired infections, prompting interest in the microbial features that allow the bug to adapt to new hosts and infection scenarios.
More broadly, given its genetic structure and diverse host range, the authors explained, S. aureus "represents an excellent model for exploring the dynamics of a bacterial pathogen at the human-animal interface."
Using Illumina HiSeq 2000 instruments, the researchers performed paired-end genome sequencing on 800 S. aureus isolates obtained in 50 countries from 43 host species — from birds and bats to rodents, rabbits, and primates. The isolates spanned 77 clonal complexes, they noted, and contained more than 115,000 SNPs across the 711,562-base core S. aureus genome.
After removing isolates that fell in divergent clades containing bugs that were more closely related to S. argenteus and S. schweitzeri, the team did a phylogenetic analysis on the remaining 783 isolates. Not surprisingly, the isolates clustered by multi-locus sequence type-based clonal complex.
Based on sequence substitution rates and interrelationships between strains infecting humans or other hosts, the researchers retraced historical host-switching events in the S. aureus tree. For example, their results suggested S. aureus microbes have moved from humans to cows many times over the last 4,000 years or so, after animal domestication events in the Neolithic period and, more recently, as agriculture and livestock farming intensified.
The team's analysis revealed apparent jumps from cattle back to humans, along with host-switching events that involved pigs, birds, rabbits, horses, and other animals. The adaptations to new hosts involved accessory genome shifts, mobile genetic element swaps, and changes in the microbe's metabolic capabilities. As S. aureus strains moved into dairy cattle, they appeared to become more adept at using the lactose sugar found in milk, for example, while certain transposable elements appeared to be under positive selection in S. aureus strains adapted to pig hosts.
When they focused on antibiotic resistance features, meanwhile, the researchers found clusters of resistance in strains known for infecting humans, pigs, or ruminants, but not in those adapted to bird hosts. Still, the pig strains were more likely to be resistant to antiseptic agents or streptomycin and tetracycline antibiotics, while human-adapted strains tended to contain a gene called sdrM that codes for a multidrug efflux pump.
"[T]he identification of the common routes for S. aureus livestock-human host species switches and distinct types of antimicrobial resistance in humans and livestock species could inform the design of more effective farm security and antibiotic treatment practices to limit the emergence of new resistant clones," the authors concluded, noting that the S. aureus results "will be relevant to other major bacterial pathogens with the capacity to spread between livestock and humans."