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Infect Immun 2019 May 21;87(6):e00085-19

Bacteriophage resistance alters antibiotic mediated intestinal expansion of enterococci.

Chatterjee A, Johnson CN, Luong P, Hullahalli K, McBride SW, Schubert AM, Palmer KL, Carlson Jr. PE, Duerkop BA


Enterococcus faecalis is a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides a diverse and virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed to combat multi-drug resistant enterococcal infections. Bacterial phage resistance represents a potential barrier to the implementation of phage therapy, emphasizing the importance of investigating the molecular mechanisms underlying the emergence of phage resistance. Using a cohort of 19 environmental lytic phages with tropism against E. faecalis, we found that these phages require the enterococcal polysaccharide antigen (Epa) for productive infection. Epa is a surface-exposed heteroglycan synthesized by enzymes encoded by both conserved and strain specific genes. We discovered that exposure to phage selective pressure favors mutation in non-conserved epa genes both in culture and in a mouse model of intestinal colonization. Despite gaining phage resistance, epa mutant strains exhibited a loss of resistance to cell wall targeting antibiotics. Finally, we show that an E. faecalis epa mutant strain is deficient in intestinal colonization, cannot expand its population upon antibiotic-driven intestinal dysbiosis and fails to be efficiently transmitted to juvenile mice following birth. This study demonstrates that phage therapy could be used in combination with antibiotics to target enterococci within a dysbiotic microbiota. Enterococci that evade phage therapy by developing resistance may be less fit at colonizing the intestine and sensitized to vancomycin preventing their overgrowth during antibiotic treatment.

Category: Journal Article
PubMed ID: #30936157 DOI: 10.1128/IAI.00085-19
PubMed Central ID: #PMC6529655
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2019-04-07 Entry Last Modified: 2019-10-27