Humans and other mammals are colonized by complex populations of microbes that constitute the microbiota. Some commensal bacteria enhance immune defenses by inducing host expression of antimicrobial factors while others secrete antimicrobial molecules that inhibit pathogens. The Eric Pamer laboratory studies interactions between pathogenic and beneficial bacteria and their mammalian hosts. Our laboratory’s research focuses on a wide range of commensal bacteria that have been characterized at the genomic, proteomic and metabolomic level and we are using gnotobiotic mice to test assembled commensal consortia for their ability to enhance resistance against pathogenic bacteria. Using these platforms, we have identified multiple novel mechanisms of antimicrobial resistance that can be exploited to reduce the risk of infection by highly antibiotic-resistant pathogens.
Recent Original Publications
Assembling symbiotic bacterial species into live therapeutic consortia that reconstitute microbiome functions. Oliveira RA, Pamer EG. Cell Host Microbe. 2023 Apr 12;31(4):472-484.
Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile. bioRxiv. 2023 Jan 12:2023.01.12.523823. doi: 10.1101/2023.01.12.523823. Preprint.PMID: 36711955
Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure. Stutz MR, Dylla NP, Pearson SD, Lecompte-Osorio P, Nayak R, Khalid M, Adler E, Boissiere J, Lin H, Leiter W, Little J, Rose A, Moran D, Mullowney MW, Wolfe KS, Lehmann C, Odenwald M, De La Cruz M, Giurcanu M, Pohlman AS, Hall JB, Chaubard JL, Sundararajan A, Sidebottom A, Kress JP, Pamer EG, Patel BK. Nat Commun. 2022 Nov 3;13(1):6615.
Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation. Becattini S, Sorbara MT, Kim SG, Littmann EL, Dong Q, Walsh G, Wright R, Amoretti L, Fontana E, Hohl TM, Pamer EG. Cell Host & Microbe. 2021 Mar 10;29(3):378-393.e5. doi: 10.1016/j.chom.2021.01.003. Epub 2021 Feb 3. PMID: 33539766
TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection. Jung HJ, Sorbara MT, Pamer EG. PLoS Pathogen. 2021 Feb 8;17(2):e1009309. doi: 10.1371/journal.ppat.1009309. eCollection 2021 Feb. PMID: 33556154
Enhancing mucosal immunity by transient microbiota depletion. Becattini S, Littmann ER, Seok R, Amoretti L, Fontana E, Wright R, Gjonbalaj M, Leiner IM, Plitas G, Hohl TM, Pamer EG. Nature Communications. 2020 Sep 8;11(1):4475. doi: 10.1038/s41467-020-18248-4. PMID: 32901029
Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity. Sorbara MT, Littmann ER, Fontana E, Moody TU, Kohout CE, Gjonbalaj M, Eaton V, Seok R, Leiner IM, Pamer EG. Cell Host & Microbe. 2020 Jul 8;28(1):134-146.e4. doi: 10.1016/j.chom.2020.05.005. Epub 2020 Jun 2. PMID: 32492369
Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine. Keith JW, Dong Q, Sorbara MT, Becattini S, Sia JK, Gjonbalaj M, Seok R, Leiner IM, Littmann ER, Pamer EG. Infection and Immunity. 2020 Mar 23;88(4):e00362-19. doi: 10.1128/IAI.00362-19. Print 2020 Mar 23. PMID: 31907198
Antibiotic Degradation by Commensal Microbes Shields Pathogens. Gjonbalaj M, Keith JW, Do MH, Hohl TM, Pamer EG, Becattini S. Infection and Immunity. 2020 Mar 23;88(4):e00012-20. doi: 10.1128/IAI.00012-20. Print 2020 Mar 23. PMID: 31964746
Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yáñez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM. New England Journal of Medicine. 2020 Feb 27;382(9):822-834. doi: 10.1056/NEJMoa1900623. PMID: 32101664
Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria. Stoma I, Littmann ER, Peled JU, Giralt S, van den Brink MRM, Pamer EG, Taur Y. Clinical Infectious Diseases. 2020 Jan 24:ciaa068. doi: 10.1093/cid/ciaa068. PMID: 31976518
Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. Kim SG, Becattini S, Moody TU, Shliaha PV, Littmann ER, Seok R, Gjonbalaj M, Eaton V, Fontana E, Amoretti L, Wright R, Caballero S, Wang ZX, Jung HJ, Morjaria SM, Leiner IM, Qin W, Ramos RJJF, Cross JR, Narushima S, Honda K, Peled JU, Hendrickson RC, Taur Y, van den Brink MRM, Pamer EG.
Nature. 2019 Aug;572(7771):665-669. doi: 10.1038/s41586-019-1501-z. Epub 2019 Aug 21. PMID: 31435014
Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium. Caballero S, Kim S, Carter RA, Leiner IM, Sušac B, Miller L, Kim GJ, Ling L, Pamer EG. Cell Host & Microbe. 2017 May 10;21(5):592-602.e4. doi: 10.1016/j.chom.2017.04.002. PMID: 28494240
Innate Lymphocyte/Ly6C(hi) Monocyte Crosstalk Promotes Klebsiella Pneumoniae Clearance. Xiong H, Keith JW, Samilo DW, Carter RA, Leiner IM, Pamer EG. Cell. 2016 Apr 21;165(3):679-89. doi: 10.1016/j.cell.2016.03.017. Epub 2016 Mar 31. PMID: 27040495
Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littmann E, van den Brink MR, Jenq RR, Taur Y, Sander C, Cross JR, Toussaint NC, Xavier JB, Pamer EG. Nature. 2015 Jan 8;517(7533):205-8. doi: 10.1038/nature13828. Epub 2014 Oct 22. PMID: 25337874
Review Articles
Microbiome-based therapeutics. Nat Rev Microbiol. 2022 Jun;20(6):365-380. doi: 10.1038/s41579-021-00667-9. Epub 2022 Jan 6.PMID: 34992261
Translating Microbiome Research From and To the Clinic. Annu Rev Microbiol. 2022 Sep 8;76:435-460. doi: 10.1146/annurev-micro-041020-022206. Epub 2022 Jun 2.PMID: 35655344
Enlisting commensal microbes to resist antibiotic-resistant pathogens. Keith JW, Pamer EG. Journal of Experimental Medicine. 2019 Jan 7;216(1):10-19. doi: 10.1084/jem.20180399. Epub 2018 Oct 11. PMID: 30309968
Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them. Sorbara MT, Pamer EG. Mucosal Immunology. 2019 Jan;12(1):1-9. doi: 10.1038/s41385-018-0053-0. Epub 2018 Jul 9. PMID: 29988120
Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Pamer EG. Science. 2016 Apr 29;352(6285):535-8. doi: 10.1126/science.aad9382. PMID: 27126035
The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens.
Kim S, Covington A, Pamer EG. Immunological Reviews. 2017 Sep;279(1):90-105. doi: 10.1111/imr.12563. PMID: 28856737
Microbiota-Based Therapies for Clostridium difficile and Antibiotic-Resistant Enteric Infections. Lewis BB, Pamer EG. Annual Review of Microbiology. 2017 Sep 8;71:157-178. doi: 10.1146/annurev-micro-090816-093549. Epub 2017 Jun 15. PMID: 28617651
Clostridium difficile colitis: pathogenesis and host defence. Abt MC, McKenney PT, Pamer EG. Nature Reviews Microbiology. 2016 Oct;14(10):609-20. doi: 10.1038/nrmicro.2016.108. Epub 2016 Aug 30. PMID: 27573580
