Genetic regulation of vibrio vulnificus hemolysin drives population heterogeneity

KathrynLynch

University of Utah

"Genetic regulation of vibrio vulnificus hemolysin drives population heterogeneity"

Individual bacterium make decisions at a genetic level as a result of various types of gene regulation; this process plays out on a population level to inform colony growth. Vibrio vulnificus is an opportunistic Gramnegative marine pathogen with a limiting growth factor of iron. Compared to other foodborne pathogens, Vibrio vulnificus has a high mortality rate and relatively poorly understood virulence mechanisms. When inside a human host, this bacteria utilizes heme as a source of iron, necessitating the ability to turn pieces of the heme acquisition system off and on in response to various environmental signals. As establishment of infection depends on Vibrio vulnificus’s ability to change from a marine to human environment, the ability to switch on the heme-intake system is an important part of establishment of initial infection. One such part of this system is the hemolysin VvhA. This toxin is excreted by the bacterium to lyse erythrocytes, thereby releasing heme into the extracellular environment where the bacteria can use it as a source of iron. This toxin is regulated by a complex set of factors including nutrient availability and quorum sensing. Exploring this gene regulatory network via bifurcation analysis reveals a complex bifurcation structure. These dynamics allow an individual bacterium to integrate a variety of signals in response to a changing environment. In particular, bistability in the system points to the likelihood of a heterogenous bacterial colony, where many bacteria benefit from a smaller number of hemolysin producers. This allows for modeling both a heterogeneous population and incorporation of the physiological mechanism by which cells make the decision to switch states. The interdependence between toxin production, nutrient availability, and colony growth result in interplay between the bacteria and their environment, allowing for insights into the overall course of infection.
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