Potassium response and homeostasis in Mycobacterium tuberculosis modulates environmental adaptation and is important for host colonization
Year: 2019
Type: article
Abstract: Successful host colonization by bacteria requires sensing and response to the local ionic milieu, and coordination of responses with the maintenance of ionic homeostasis in the face of changing conditions.We previously discovered that Mycobacterium tuberculosis (Mtb) responds synergistically to chloride (Cl -) and pH, as cues to the immune status of its host.This raised the intriguing concept of abundant ions as important environmental signals, and we have now uncovered potassium (K + ) as an ion that can significantly impact colonization by Mtb.The bacterium has a unique transcriptional response to changes in environmental K + levels, with both distinct and shared regulatory mechanisms controlling Mtb response to the ionic signals of K + , Cl -, and pH.We demonstrate that intraphagosomal K + levels increase during macrophage phagosome maturation, and find using a novel fluorescent K + -responsive reporter Mtb strain that K + is not limiting during macrophage infection.Disruption of Mtb K + homeostasis by deletion of the Trk K + uptake system results in dampening of the bacterial response to pH and Cl -, and attenuation in host colonization, both in primary murine bone marrow-derived macrophages and in vivo in a murine model of Mtb infection.Our study reveals how bacterial ionic homeostasis can impact environmental ionic responses, and highlights the important role that abundant ions can play during host colonization by Mtb. Author summaryTuberculosis is the leading cause of death from infectious diseases globally, and knowledge of the fundamental biology underlying successful host colonization by Mycobacterium tuberculosis (Mtb) is critical for understanding its pathogenicity.Our study focuses on one such important facet-the ability of Mtb to sense and respond to changing environmental ionic signals, and its relation to maintenance of bacterial ionic homeostasis.Potassium (K + ) is the most abundant ion in both mammalian and bacterial cells, but
Source: PLoS Pathogens
Institution: Tufts University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,350
OpenAlex ID: W2913098102