Browsing by Author "Rangel, Jonathan"
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Item A Proteomic Signature of Dormancy in an Actinobacterium: Micrococcus luteus(2017) Mali, Sujina; Rangel, Jonathan; Mitchell, Morgan; Havis, Spencer; Bodunrin, Abiodun; Khan, Arshad; Widger, William R.; Bark, Steven J.This project was completed with contributions from Arshad Khan from the Department of Pathology and Laboratory Medicine, UT Health Science Center, Houston.Item Resuscitation Promoting Factor from Micrococcus luteus(2017-10-12) Nielsen, Carolyn; Rangel, Jonathan; Bodunrin, AbiodunMany bacteria become dormant when nutrient deprived or in response to environmental stress. Mycobacterium tuberculosis (TB) becomes dormant when challenged by stress or antibiotics, which leads to antibiotic resistance. According to the World Health Organization approximately one-third of the world’s population contain latent TB! Preventing bacteria from entering dormancy is critical. Dormant cells are viable but nonculturable (VBNC) and require a resuscitation promoting factor (Rpf), a protein that is required to start growth and replication. Micrococcus luteus (ML) is a nonpathogenic actinobacteria closely related to TB with a well-studied dormancy response. ML Rpf can resuscitate dormant TB suggesting they share a common dormancy mechanism. We have cloned and extracted full length Rpf from ML and are characterizing ML resuscitation by Rpf to determine the critical amino acids that activate dormant bacteria. We are currently subcloning the resuscitation domain.Item The Universal Stress Proteins of Micrococcus Luteus Are Metabolic Regulators That Confer Resistance to a Diverse Set of Stress Factors(2021-12) Rangel, Jonathan; Widger, William R.; Şen, Mehmet; Bawa-Khalfe, Tasneem; May, Elebeoba E.The bacterial stress response systems have developed and evolved over the millennia to deal with the changing environmental conditions experienced by all the bacterial species. A common form of stress mitigation is the development of the dormant phenotype, a process by which bacteria enter a state of sustained arrested growth that renders them nearly impervious to most stress conditions including antibiotics. The dormancy state presents a growing problem in the medical field as it is implied to be one of the root causes behind chronic infections including latent Mycobacterium tuberculosis. The biochemical mechanisms that regulate the differentiation into dormancy are not fully understood, but a common link points to the possible role of universal stress proteins as a major contributor to the maintenance of the dormant phenotype. The universal stress proteins are a class of proteins that have been identified as being highly upregulated during stress response in a variety of bacteria and have been shown to be vital in maintaining cell viability during stress conditions. Our previous work has established that Micrococcus luteus presents a model example of the dormancy phenotype and that the universal stress protein (WP_010079616.1) is vital to maintain cell viability during the hypoxic induced dormant state. We have previously identified that the universal stress protein (WP_010079712.1) helps regulate growth during the initial inoculation stages alongside a resuscitation-promoting factor protein. A genetic knockout of universal stress protein (WP_010080184.1) increased the susceptibility to hydrogen peroxide stress and cause the cells to increase biofilm production during nutrient starvation. RNASeq analysis of the nutrient starved ML_Δusp616::kan transcriptome revealed a dysregulation of multiple resistance mechanisms by failing to suppress transposable elements, failing to downregulate metabolic processes, and loss of Rho transcription factor control through failure to upregulate NusG. Characterization of the Usp616 revealed that is both a homodimer forming and ATP binding variant of Usp. M. luteus is a model organism for determining the mechanisms by which Usps regulate stress response including the entering the VBNC state.