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Sci Transl Med DOI:10.1126/scitranslmed.aat8418

Impact of antibiotic treatment and host innate immune pressure on enterococcal adaptation in the human bloodstream.

Publication TypeJournal Article
Year of Publication2019
AuthorsVan Tyne, D, Manson, AL, Huycke, MM, Karanicolas, J, Earl, AM, Gilmore, MS
JournalSci Transl Med
Date Published2019 Apr 10

Multidrug-resistant enterococcal strains emerged in the early 1980s and are now among the leading causes of drug-resistant bacterial infection worldwide. We used functional genomics to study an early bacterial outbreak in patients in a Wisconsin hospital between 1984 and 1988 that was caused by multidrug-resistant The goal was to determine how a clonal lineage of became adapted to growth and survival in the human bloodstream. Genome sequence analysis revealed a progression of increasingly fixed mutations and repeated independent occurrences of mutations in a relatively small set of genes. Repeated independent mutations suggested selection within the host during the course of infection in response to pressures such as host immunity and antibiotic treatment. We observed repeated independent mutations in a small number of loci, including a little studied polysaccharide utilization pathway and the locus. Functional studies showed that mutating these loci rendered better able to withstand antibiotic pressure and innate immune defenses in the human bloodstream. We also observed a shift in mutation pattern that corresponded to the introduction of carbapenem antibiotics in 1987. This work identifies pathways that allow enterococci to survive the transition from the human gut into the bloodstream, enabling them to cause severe bacteremia associated with high mortality.


Alternate JournalSci Transl Med
PubMed ID30971455
Grant ListP01 AI083214 / AI / NIAID NIH HHS / United States
R00 EY028222 / EY / NEI NIH HHS / United States