(176ag) Phospholipid Remodeling Via Exogenous Polyunsaturated Fatty Acid Uptake Modulates Stress Resistance in Vibrio Cholerae

Antibiotic-resistant pathogens represent an escalating threat to public health worldwide, substantially increasing the burden of healthcare- and community-acquired infections. Several factors contribute to the emergence and spread of this threat, including but not limited to improper antibiotic use and prescriptions in health-care settings and the community, increasing global travel and migration from countries that have higher levels of antibiotic-resistant pathogens, and an insufficient number of new antibiotics under development. According to the World Health Organization, rising rates of resistance among Gram-negative bacteria (such as Vibrio cholerae) are of particular concern. These bacteria have evolved a number of endogenous membrane remodeling strategies to sense and adapt to their environment. However, another membrane remodeling strategy employed by these bacteria, the uptake and assimilation of exogenous fatty acids, remains largely unexplored. Here, we seek to address this knowledge gap through the pursuit of two specific aims: (1) determining the extent to which phospholipid remodeling through uptake of exogenous PUFAs impacts antimicrobial resistance in Vibrio; and (2) identifying the impact of phospholipid composition on the behavior of the Vibrio outer membrane. For Aim #1, having previously established that the presence of exogenous PUFAs impacts Vibrio’s resistance to polymyxin B, we will measure the susceptibility of Vibrio to antimicrobial peptides present in the human intestine and fish. These assays will be conducted in the presence of individual PUFAs for a control strain as well as mutants lacking the ability to modify LPS. In Aim #2, we will simulate models of the Vibrio outer membrane using molecular dynamics simulation in order to analyze the influence of fatty acid composition on membrane fluidity, porosity, and susceptibility to antimicrobials.