Research ArticleBACTERIAL INFECTIONS

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

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Science Translational Medicine  10 Apr 2019:
Vol. 11, Issue 487, eaat8418
DOI: 10.1126/scitranslmed.aat8418

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Friend turned foe

Enterococci are commensal bacteria found in the gut of most humans. Strains have arisen that are able to survive disinfection protocols in hospitals and that are resistant to antibiotics, resulting in the spread of this bacterium from patient to patient. To elucidate how enterococci have made this adaptation, Van Tyne et al. analyzed the genomes of enterococcal strains from an early outbreak of bloodstream infection in a hospital ward in the mid-1980s. They report the genetic changes that enabled the enterococci causing the human bloodstream infection to survive elimination by the host innate immune system and antibiotic therapy.

Abstract

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 Enterococcus faecalis. The goal was to determine how a clonal lineage of E. faecalis 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 cydABDC locus. Functional studies showed that mutating these loci rendered E. faecalis 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.

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