THE MOLECULAR BASIS OF SURVIVAL TO MEMBRANE-TARGETING BACTERIAL CONTROL METHODS, AND IMPLICATIONS FOR DISEASE CONTROL

Disruption of bacterial outer membranes (OM) by antimicrobial agents is a major area of promise for biocontrol and plant disease resistance. Examples include bacterially produced toxins, termed tailocins, which show excellent promise for specific and engineerable prophylaxis. Additionally, LPS targeting antimicrobial peptides (AMP) are the major difference between Huanglongbing (HLB) resistant and susceptible plants. Indeed, plants are known to produce an array of AMPs that kill microbes through membrane disruption. Despite this promise, we've shown that bacteria can enter temporary physiological states that make them tolerant to membrane-active treatments, a phenomenon termed persistence. Such persistence complicates the effectiveness of these treatments. Moreover, modeling has predicted for many antimicrobials, including those that are OM-targeting, that persistence can speed the evolution of resistance, further impeding our ability to deploy these agents for long-term control. Thus, understanding the prevalence and mechanisms of survival to OM-targeting treatments will be critical for determining under what conditions these treatments will be durable and effective, and for designing resistance mitigation strategies. We aim to 1) understand the physiology and genetics that underlie bacterial persistence to multiple OM-targeting agents, 2) determine whether there is overlap in persistence mechanisms to distinct OM-targeting agents, and 3) assess empirically whether increased persistence can result in increased rates of resistance, as well as how persistence contributes to treatment survival in a plant host environment. The results of this research will improve our ability to predict the potential outcomes of OM-targeting antimicrobials and modify treatment strategies to ensure their long-term effectiveness.