We have begun to address the interplay between the resident host microbiota and bacterial pathogens such as Salmonella enterica and Escherichia coli during enteric infection, and the impact of their interactions on host immune response, including inflammation. We are also studying the shifts in microbial populations that occur in inflammatory bowel diseases. Some of our seminal findings in this area indicate that composition of the microbiota plays a significant role in susceptibility and resistance to enteric diseases.
We’ve been using clinically relevant doses of various antibiotics to cause defined shifts in microbiota and examining how these shifts translate into host susceptibility to infection with enteric pathogens. We have found that animals with some shifts in microbiota result in a marked increase in susceptibility to enteric
infections while others do not, and are now working to determine which host, pathogen and resident microbial factors are responsible for the observed effects.
Moreover, we are looking at the role of the microbiota in the development of immune responses. For example, we have shown that Th17 cell development is critically determined by microbial composition. We are probing other immune responses, both innate and acquired, to further examine the role in immune development and disease. Ultimately, this work will further help us to understand the interplay between the host, the pathogen and the microbiota during infectious diseases, eventually translating into improvements in the management and prevention of enteric infections. Along with colleagues at the Michael Smith Laboratories, Dr. Finlay published “Recent Advances in Understanding Enteric Pathogenic Escherichia coli” in Clinical Microbiology Reviews.
Relevant NGDI Articles
15-Deoxy-Δ12,14-prostaglandin J2 inhibits macrophage colonization by Salmonella enterica serovar Typhimurium. Buckner MM, Antunes LC, Gill N, Russell SL, Shames SR, Finlay BB. PLoS One. 2013 Jul 26;8(7):e69759.
A case for antibiotic perturbation of the microbiota leading to allergy development. Reynolds LA, Finlay BB. Expert Rev Clin Immunol. 2013 Nov;9(11):1019-30.
A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection. Marchiando AM, Ramanan D, Ding Y, Gomez LE, Hubbard-Lucey VM, Maurer K, Wang C, Ziel JW, van Rooijen N, Nuñez G, Finlay BB, Mysorekar IU, Cadwell K. Cell Host Microbe. 2013 Aug 14;14(2):216-24.
A fresh look at the hygiene hypothesis: how intestinal microbial exposure drives immune effector responses in atopic disease. Brown EM, Arrieta MC, Finlay BB. Semin Immunol. 2013 Nov 30;25(5):378-87.
A novel subcellular machine contributes to basal junction remodeling in the seminiferous epithelium. Du M, Young J, De Asis M, Cipollone J, Roskelley C, Takai Y, Nicholls PK, Stanton PG, Deng W, Finlay BB, Vogl AW. Biol Reprod. 2013 Mar 14;88(3):60.
An antibiotic-altered microbiota provides fuel for the enteric foe. Stiemsma LT, Turvey SE, Finlay BB. Cell Res. 2014 Jan;24(1):5-6.
Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell α-defensins. Menendez A, Willing BP, Montero M, Wlodarska M, So CC, Bhinder G, Vallance BA, Finlay BB. J Innate Immun. 2013;5(1):39-49.
Combating enteropathogenic Escherichia coli (EPEC) infections: the way forward. Donnenberg MS, Finlay BB. Trends Microbiol. 2013 Jul;21(7):317-9.
Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis. Romain G, Tremblay S, Arena ET, Antunes LC, Covey S, Chow MT, Finlay BB, Menendez A. BMC Microbiol. 2013 Oct 29;13:238.
EscE and EscG are cochaperones for the type III needle protein EscF of enteropathogenic Escherichia coli. Sal-Man N, Setiaputra D, Scholz R, Deng W, Yu AC, Strynadka NC, Finlay BB. J Bacteriol. 2013 Jun;195(11):2481-9.
Global impact of Salmonella pathogenicity island 2-secreted effectors on the host phosphoproteome. Imami K, Bhavsar AP, Yu H, Brown NF, Rogers LD, Finlay BB, Foster LJ. Mol Cell Proteomics. 2013 Jun;12(6):1632-43.
In vitro and in vivo model systems for studying enteropathogenic Escherichia coli infections. Law RJ, Gur-Arie L, Rosenshine I, Finlay BB. Cold Spring Harb Perspect Med. 2013 Mar 1;3(3):a009977. Review.
Manipulation of innate immunity by a bacterial secreted peptide: lantibiotic nisin Z is selectively immunomodulatory. Kindrachuk J, Jenssen H, Elliott M, Nijnik A, Magrangeas-Janot L, Pasupuleti M, Thorson L, Ma S, Easton DM, Bains M, Finlay B, Breukink EJ, Georg-Sahl H, Hancock RE. Innate Immun. 2013 Jun;19(3):315-27.
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. Amaral JJ, Antunes LC, de Macedo CS, Mattos KA, Han J, Pan J, Candéa AL, Henriques Md, Ribeiro-Alves M, Borchers CH, Sarno EN, Bozza PT, Finlay BB, Pessolani MC. PLoS Negl Trop Dis. 2013 Aug 15;7(8):e2381.
Microbiology: EHEC downregulates virulence in response to intestinal fucose. Keeney KM, Finlay BB. Curr Biol. 2013 Feb 4;23(3):R108-10. Link
Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Russell SL, Gold MJ, Willing BP, Thorson L, McNagny KM, Finlay BB. Gut Microbes. 2013 Mar-Apr;4(2):158-64. Review.
Recent advances in understanding enteric pathogenic Escherichia coli. Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. Clin Microbiol Rev. 2013 Oct;26(4):822-80.
Studying microbial pathogenesis and bacterial diseases. Interview by Hannah Branch. Finlay BB. Future Microbiol. 2013 Jun;8(6):709-10.
Targeting the type III secretion system to treat bacterial infections. Marshall NC, Finlay BB. Expert Opin Ther Targets. 2014 Feb;18(2):137-52.
The enterohemorrhagic Escherichia coli effector protein NleF binds mammalian Tmp21. Olsen RL, Echtenkamp F, Cheranova D, Deng W, Finlay BB, Hardwidge PR. Vet Microbiol. 2013 May 31;164(1-2):164-70.
The role of the immune system in governing host-microbe interactions in the intestine. Brown EM, Sadarangani M, Finlay BB. Nat Immunol. 2013 Jul;14(7):660-7. Review.
The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity. Bhavsar AP, Brown NF, Stoepel J, Wiermer M, Martin DD, Hsu KJ, Imami K, Ross CJ, Hayden MR, Foster LJ, Li X, Hieter P, Finlay BB. PLoS Pathog. 2013;9(7):e1003518.
Bacterial effector interplay: A new way to view effector function. Shames SR and Finlay BB. Trends Microbiol 2012 20(5):214-219.
Defining a healthy human gut microbiome: Current concepts, future directions, and clinical applications. Backhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V and Finlay BB. Cell Host and Microbe 2012 12(5):611-622.
Effective adjunctive therapy by an innate defense regulatory peptide in a pre-clinical model of severe malaria. Achtman AH, Pilat S, Law CW, Lynn DJ, Janot L, Mayer M, Ma S, Kindrachuk J, Finlay BB, Brinkman FSL, Smyth GK, Hancock REW and Schofield L. Science Transl Med 2012 4(135):135ra64.
EscA is a crucial component of the type III secretion system of enteropathogenic Escherichia coli. Sal-Man N, Biemans-Oldehinkel E, Sharon D, Croxen MA, Scholz R, Foster LJ and Finlay BB. J Bacteriol 2012194(11):2819-2828.
Identifying an immune signature against invasive Salmonella. Ferreira RBR and Finlay BB. Proc Natl Acad Sci USA 2012 109(13):4721-4722.
Neutrophil Elastase Alters the Murine Gut Microbiota Resulting in Enhanced Salmonella Colonization. Gill N, Ferreira RBR, Antunes LCM, Willing BP, Sekirov I, Al-Zahrani F, Hartmann M and Finlay BB PLoS ONE 2012 7(11)
Oxysterol-binding protein (osbp) enhances replication of intracellular salmonella and binds the salmonella spi-2 effector ssel via its n-terminus. Auweter SD, Yu HB, Arena ET, Guttman JA and Finlay BB. Microbes Infect 2012 14(2):148-154.
Repression of salmonella enterica phop expression by small molecules from physiological bile. Antunes LCM, Wang M, Andersen SK, Ferreira RBR, Kappelhoff R, Han J, Borchers CH and Finlay BB. J Bacteriol 2012 194(9):2286-2296.
Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens. Cortes-Vieyra R, Bravo-Patino A, Valdez-Alarcon JJ, Juarez MC, Finlay BB and Baizabal-Aguirre VM. J Inflamm 2012 9:23
Special edition of Gut Microbes. McCormick B and Finlay B. Gut Microbes 2012 3(2):61.
The enemy within us: Lessons from the 2011 European Escherichia coli O104:H4 outbreak. Karch H, Denamur E, Dobrindt U, Finlay BB, Hengge R, Johannes L, Ron EZ, Tonjum T, Sansonetti PJ and Vicente M. EMBO Mol Med 2012 4(9):841-848.
The zinc regulated antivirulence pathway of Salmonella is a multiprotein immunoglobulin adhesion system. Prehna G, Li Y, Stoynov N, Okon M, Vuckovic M, McIntosh LP, Foster LJ, Finlay BB and Strynadka NCJ. J Biol Chem 2012 287(39):32324-32337.
Type III effector-mediated processes in Salmonella infection. Van Der Heijden J and Finlay BB. Future Microbiol 2012, 7(6):685-703.
A comprehensive study of the contribution of Salmonella enterica serovar Typhimurium SPI2 effectors to bacterial colonization, survival, and replication in typhoid fever, macrophage, and epithelial cell infection models. Buckner MMC, Croxen MA, Arena E, and Finlay BB. Virulence 2011, 2:3:208-216.
Effect of antibiotic treatment on the intestinal metabolome. Antunes LCM, Han J, Ferreira RBR, Lolić P, Borchers CH, and Finlay BB. Antimicrobial Agents and Chemotherapy 2011, Vol55:4:1494-1503.
Protective role of Akt2 in Salmonella enterica serovar typhimurium-induced gastroenterocolitis. Kum WWS, Lo BC, Yu HB, and Finlay BB. Infection and Immunity 2011, Vol79:7:2554-2566.
The Salmonella enterica PhoP directly activates the horizontally acquired SPI-2 gene sseL and is functionally different from a S. bongori ortholog. Gal-Mor O, Elhadad D, Deng W, Rahav G, and Finlay BB. PLoS One 2011, 6:5:20024
The human transcriptome during nontyphoid Salmonella and HIV coinfection reveals attenuated NFjB-mediated inflammation and persistent cell cycle disruption. Schreiber F, Lynn DJ, Houston A, Peters J, Mwafulirwa G, Finlay B, Brinkman FSL, Hancock REW, Heyderman RS, Dougan G, and Gordon MA. The Journal of Infectious Diseases 2011, 204:1237-45.