Adapt to survive, thrive and colonize: exploring human colonization by S. aureus
A new approach to the investigation of bacterial adaptations could help improve the prevention and treatment of bacterial infections.
An international research team from the Wellcome Sanger Institute (Hixton, UK), the University of Cambridge (UK) and the Spanish National Research Council (Madrid, Spain) have used a new approach to investigate the bacterial adaptations of Staphylococcus aureus during colonization of human hosts. This genome-wide enrichment approach could be applied in further studies of bacterial pathogens and their adaptive evolution, helping to improve the prevention and treatment of bacterial infections.
Commensal and opportunistic bacteria are commonly found in or on the body and normally do not cause harm. Staphylococcus aureus (S. aureus) is one example of such bacteria, living on almost 30% of the global human population, primarily found in the lower nostrils of humans, as well as on the skin and in the intestines. However, when the opportunity arises, if the epithelial barrier breaks or the immune system is weakened, S. aureus can become pathogenic. S. aureus infections can range from superficial skin and soft tissue infections to life-threatening infections such as sepsis and pneumonia.
Colonization of the host is an important risk factor for S. aureus infection as during this period, the bacteria have the opportunity to adapt to survive on the host, and the colonizing strain is frequently observed to be the cause of an S. aureus infection. While some studies have investigated the bacterial adaptions of S. aureus during colonization, our understanding remains incomplete.
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To increase our understanding, the team set out to investigate the bacterial adaptations of S. aureus during the colonization of their natural environment. They hypothesized that S. aureus faces common selective pressures when adapting to new hosts, with advantageous mutations expected to be enriched in the same genes across multiple S. aureus colonizing strains.
To test this hypothesis, the team compiled a genomic dataset of 3497 S. aureus isolates. 3060 of these isolates from a total of 791 individuals were analyzed to identify evidence of bacterial adaptation in recently diverged populations. The team then applied a genome-wide mutation enrichment approach to identify loci in the S. aureus genome that exhibit evidence of parallel and convergent evolution. These loci may represent signals of adaptation during host colonization.
These investigations revealed that genes encoding nasD, the nitrite reductase large subunit, and ureG, the urease accessory protein, were among the most mutation enriched in colonizing isolates. This made nitrogen metabolism the most mutated metabolic process in the isolates, highlighting this pathway as a potential key for the colonization of humans by S. aureus.
To further investigate bacterial adaptations, an additional 4090 isolate genomes from 731 individuals were compiled into a new genomic database for analysis. The team applied the same genome-wide enrichment approach to the combined datasets (7150 isolate genomes from 1593 individuals), revealing the genes already identified with enriched mutations plus an additional eight genes. The additional genes included SraP, serin-rich adhesion for binding to platelets involved in adhesion and invasion, highlighting further pathways for investigation
“Through our new analysis, we were able to study these strains in their natural habitat; highlighting previously unknown mutations that give certain Staphylococcus aureus strains the upper hand” commented senior author Ewan Harrison.
This methodological approach highlights a new avenue through which to explore the adaptive evolution of bacterial pathogens in their natural habitats and has opened up new lines of inquiry for the prevention and treatment of S. aureus infections.
