Vancomycin resistant Enterococcus (VRE) and Listeria monocytogenes
VRE is an antibiotic-resistant pathogen that commonly causes bloodstream infections in patients undergoing complex medical treatments. Treatment with antibiotics can destroy the microbiota of the gastrointestinal tract, rendering patients highly vulnerable to dense colonization with VRE, increasing the risk of bloodstream infection. Dense colonization with VRE also leads to contamination of healthcare settings and patient-to-patient transmission. A healthy microbiota can clear VRE from the gut and we recently assembled a consortium of 4 commensal bacterial strains that mediates VRE clearance. We are identifying mechanisms of VRE clearance with the goal of developing approaches to reduce VRE infections. Our laboratory has identified a specific commensal bacterial strain that produces a bacteriocin that inhibits VRE growth. The bacteriocin is also highly effective at suppressing the growth of Listeria monocytogenes, an important food-borne pathogen. We are also investigating the interaction of modified bile acids with VRE and its ability to persist in the intestinal lumen. Longitudinal, multi-parallel DNA sequence analyses demonstrate the rapid evolution of VRE in the intestinal lumen and are providing important insights into the epidemiology of intestinal colonization with antibiotic-resistant pathogens in the healthcare setting.
VRE-specific Publications
Becattini S, Littmann ER, Seok R, Amoretti L, Fontana E, Wright R, Gjonbalaj M, Leiner IM, Plitas G, Hohl TM, Pamer EG. Enhancing mucosal immunity by transient microbiota depletion. Nat Commun. 2020 Sep 8;11(1):4475. doi: 10.1038/s41467-020-18248-4.
Sorbara MT, Littmann ER, Fontana E, Moody TU, Kohout CE, Gjonbalaj M, Eaton V, Seok R, Leiner IM, Pamer EG. Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity. Cell Host Microbe. 2020 Jul 8;28(1):134-146.e4. doi: 10.1016/j.chom.2020.05.005.
Gjonbalaj M, Keith JW, Do MH, Hohl TM, Pamer EG, Becattini S. Antibiotic Degradation by Commensal Microbes Shields Pathogens. Infect Immun. 2020 Mar 23;88(4):e00012-20. doi: 10.1128/IAI.00012-20.
Keith JW, Dong Q, Sorbara MT, Becattini S, Sia JK, Gjonbalaj M, Seok R, Leiner IM, Littmann ER, Pamer EG. Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine. Immun. 2020 Mar 23;88(4):e00362-19. doi: 10.1128/IAI.00362-19. Print 2020 Mar 23.
Kim SG, Becattini S, Moody TM, Shliaha PV, Littmann ER, Seok R, Gjonbalaj M, Eaton V, Fontana E, Amoretti L, Wright R, Caballero S, Wang Z-MX, Jung H-J, Morjaria SM, Leiner IM, Qin W, Ramos RJJF, Cross JR, Narushima S, Hon da K, Peled JU, Hendrickson RC, Taur Y, van den Brink MRM, Pamer EG. Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. Nature. 2019;
Dubin KA, Mathur D, McKenney PT, Taylor BP, Littmann ER, Peled JU, van den Brink MRM, Taur Y, Pamer EG, Xavier JB. Diversification and evolution of Vancomycin-resistant Enterococcus faecium during intestinal domination. Infection and Immunity. 2019; 87(7). Pii: e00102-19.
McKenney PT, Yan J, Vaubourgeix J, Becattini S, Lampen N, Motzer A, Larson PJ,Dannaoui D, Xavier JB, Pamer EG. Bile acid induced morphotype switch mediatesintestinal colonization by vancomycin resistant Enterococcus. Cell Host and Microbe 2019; 25(5):695-705.
Caballero S, Kim S, Carter RA, Leiner IM, Sušac B, Miller L, Kim GJ, Ling L, Pamer EG. Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium. Cell Host Microbe. 2017; 21(5):592-602.
Abt MC, Buffie CG, Susac B, Becattini S, Carter RA, Leiner I, Keith JW, Artis Osborne LC, Pamer EG. TLR-7 activation enhances IL-22-mediated colonization Resistance against vancomycin-resistant Enterococcus. Science Translational Medicine. 2016; 8(327):327ra25.
Caballero S, Carter R, Ke X, Susac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG. Distinct but Spatially Overlapping Intestinal Niches for Vancomycin Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae. PLoS Pathogens. 2015; 9(11):e1005132.
Becattini S, Littmann ER, Carter RA, Kim SG, Morjaria SM, Ling L, Gyaltshen Y, Fontana E, Taur Y, Leiner IM, Pamer EG. Commensal microbes provide first line defense against Listeria monocytogenes infection Journal of Experimental Medicine. 2017; 214(7):1973-1989.
