Characterization of Burkholderia Persistence Determinants and Antibiotic Resistance
Abstract
Antibiotic resistance is a perennial and escalating problem for treatment of many clinically important bacterial infections and is a major concern for higher mortality bio threat agents. Target modification, efflux, and detoxification mechanisms are well-studied strategies used by bacteria to circumvent antibiotic treatment. However, there is a growing and emerging recognition that persister cells are critical aspects and contributors to the antibiotic resistance dilemma. Persisters are dormant bacterial cells that form in bacterial populations either stochastically or in response to specific environmental cues. In some bacteria, a variety of non-inheritable mechanisms have been implicated in this phenotype, sometimes involving toxin/antitoxin expression systems. A recent report showed that B. pseudomallei can enter a persister state under anaerobic conditions and can be resurrected after 1 year. To support the identification of mechanisms that induce the persister phenotypes, as well as mechanisms to inhibit persister conversion, we propose a multidisciplinary “Omics” approach to: identifying Burkholderia specific persister determinants (specific aim 1); assessing host factors and novel persister inducing signals (specific aim 2); determining the conservation of persistence strategies across a range of virulent strains of B. pseudomallei; characterize transcriptomic, proteomic, and epigenetic modifications that induce a persister state; generate deletion mutations that support persister state induction and suppression; and design qRT-PCR assays for identification of transcriptomic markers for induction of persister cells.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 26, 2016
- Source ID
- HDTRA11510015
Entities
People
- William Nierman
Organizations
- Defense Threat Reduction Agency
- J. Craig Venter Institute