Ph.D., University of California, Los Angeles, 2008
B.S., Rutgers University, 2002
Honors and Awards
- Princeton Engineering Council Excellence in Teaching Award, 2016
- Howard B. Wentz, Jr. Junior Faculty Award, 2015
- NSF CAREER Award, 2015-2020
- HHMI Postdoctoral Associate, Boston University, 2008-2010
- UCLA Dissertation Year Fellowship, 2007-08
- UCLA Quality of Graduate Education Stipend, 2006
- Arco Graduate Student Fellowship, 2006
- California NanoSystems Institute (CNSI) Graduate Student Fellowship, 2002-03
- Associated Faculty, Department of Molecular Biology
With the ever-increasing incidence of antibiotic-resistant infections and a weak pipeline of new antibiotics, our antibiotic arsenal is in danger of becoming obsolete. Since conventional antibiotic discovery is failing to keep pace with the rise of resistance, fresh perspectives and novel methodologies are needed to address this critical public health issue. The main focus of our group is to use both computational and experimental techniques in systems biology, synthetic biology, and metabolic engineering to understand and combat infectious disease. We focus on two key areas: host-pathogen interactions and bacterial persistence toward antibiotics.
Host-pathogen interactions: The increase in the frequency of antibiotic-resistant strains has researchers searching for new antimicrobials or novel ways to potentiate current therapeutics. One exciting approach with great potential is antivirulence therapy, which focuses on disrupting the ability of a pathogen to infect a host. Rather than targeting essential bacterial functions as current antibiotics do, antivirulence therapy targets essential host-pathogen interactions required for infection such as adhesion, quorum sensing, and susceptibility to immune attack. These therapies are less prone to resistance development due to their ability to provide selective pressure only within the host, and have the potential to greatly expand our antibacterial capabilities. In this area, we leverage our knowledge and understanding of bacterial metabolism and stress responses to increase the susceptibility of pathogens to killing by various immune antimicrobials, including reactive oxygen species and reactive nitrogen species.
Bacterial persistence: Bacterial persistence is a non-genetic, non-inherited (epigenetic) ability in bacteria to tolerate antibiotics and other stress. This distinct physiological state is thought to cause chronic and recurrent infection, and represents an insurance policy in which a small portion of cells enter dormancy and sacrifice their ability to replicate in order to survive stress at a future time. The proportion of persisters in a population varies by strain and environment (generally 1 in 100 to 1 in 1,000,000 cells), and the mechanism of persister formation as well as the content of their physiology remain elusive. A major goal of our group is to understand the physiology of persisters that allows them to tolerate what for other cell types are lethal treatments with antibiotics. This work will provide knowledge that could be leveraged to eliminate persisters as a source of chronic infection.
- Mok WWK, Brynildsen MP. Timing of DNA damage responses impacts persistence to fluoroquinolones. Proc Natl Acad Sci U S A, 2018 Jul 3;115(27):E6301-E6309.
- Robinson JL, Brynildsen MP. Discovery and dissection of metabolic oscillations in the nitric oxide response network of Escherichia coli. Proc Natl Acad Sci U S A, 2016 Mar 22;113(12):E1757-66.
- Orman MA, Brynildsen MP. Inhibition of stationary phase respiration impairs persister formation in E. coli. Nature Communications, 2015 Aug 6;6:7983.
- Amato SM, Orman MA, Brynildsen MP. Metabolic control of persister formation in Escherichia coli. Molecular Cell, 2013 May 23;50(4):475-87.
- Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature, 2011 May 12; 473(7346):216-20.