I am interested in environmentally dependent regulation of bacterial gene expression and survival mechanisms of tuberculosis bacilli. I am specifically focused on the problem of persistence, the ability of small populations of tuberculosis bacilli to survive antibiotic treatment despite lacking alleles that code for genotypic drug resistance. The phenomenon of persistence may be the basis of the need for lengthy treatment regimens to cure tuberculosis and could also contribute the ability of the bacteria to establish a latent infection. I have characterized the transcriptome of tuberculosis persister cells to identify genes that may be involved in the phenomenon, and have created mutant strains defective for persistence. I am in the process of characterizing these mutants using mouse models and various -omics technologies and work collaboratively on other projects that require systems biological approaches.

Tiwari S, van Tonder AJ, Vilchèze C, Mendes V, Thomas SE, Malek A, Chen B, Chen M, Kim J, Blundell TL, Parkhill J, Weinrick B, Berney M, Jacobs WR Jr. Arginine-deprivation-induced oxidative damage sterilizes Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):9779-9784.

Vilchèze C, Hartman T, Weinrick B, Jain P, Weisbrod TR, Leung LW, Freundlich JS, Jacobs WR Jr. Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4495-4500.

Jain P*, Weinrick BC*, Kalivoda EJ, Yang H, Munsamy V, Vilchèze C, Weisbrod T, Larsen MH, O’Donnell MR, Pym A, Jacobs WR Jr. Dual-Reporter Mycobacteriophages (Φ2DRMs) Reveal Pre-existing Mycobacterium tuberculosis Persistent Cells in Human Sputum. MBio. 2016 Oct 25;7(5). pii: e01023-16. *equal contribution

Petro CD, Weinrick B, Khajoueinejad N, Burn C, Sellers R, Jacobs WR Jr, Herold BC. HSV-2 ∆gD Elicits FcγR-Effector Antibodies that Protect Against Clinical Isolates. JCI Insight. 2016 Aug 4;1(12):e88529.

Packiam M, Weinrick B, Jacobs Jr. WR, Maurelli AT. Structural characterization of muropeptides from Chlamydia trachomatis peptidoglycan by mass spectrometry resolves ""chlamydial anomaly"". Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11660-5.

Wang F, Sambandan D, Halder R, Wang J, Batt SM, Weinrick B, Ahmad I, Yang P, Zhang Y, Kim J, Hassani M, Huszar S, Trefzer C, Ma Z, Kaneko T, Mdluli KE, Franzblau S, Chatterjee AK, Johnson K, Mikusova K, Besra GS, Fütterer K, Jacobs WR Jr, Schultz PG. Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. Proc Natl Acad Sci U S A. 2013 Jun 17.

Vilchèze C, Hartman T, Weinrick B, Jacobs WR Jr. Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nat Commun. 2013; 4:1881.

Kalscheuer R, Syson K, Veeraraghavan U, Weinrick B, Biermann KE, Liu Z, Sacchettini JC, Besra G, Bornemann S, Jacobs WR Jr. Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. Nat Chem Biol. 2010 May; 6 (5): 376-84.

Weinrick B, Dunman PM, McAleese F, Murphy E, Projan SJ, Fang Y, Novick RP. Effect of mild acid on gene expression in Staphylococcus aureus. J Bacteriol. 2004 Dec; 186 (24): 8407-23.

Limbago B, Penumalli V, Weinrick B, Scott JR. Role of streptolysin O in a mouse model of invasive group A streptococcal disease. Infect Immun. 2000 Nov; 68 (11): 6384-90.