Pathogenicity of Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage


Mycobacterium tuberculosis (Mtb) is a highly successful human pathogen, representing the leading bacterial cause of death worldwide. Mtb infects macrophages and it adapts to the hostile intracellular milieu of this cell by exploiting the plasticity of its central carbon metabolism machinery. While several studies have detailed the bacterial adaptations that accompany infection, it is still unclear whether this process also involves engagement with host metabolic pathways. We therefore profiled the kinetic flux of host cell metabolites in macrophages that were infected with differently virulent Mtb strains. Interestingly, we found that Mtb pathogenicity was indeed intimately linked to its capacity to regulate host cell metabolism. A unique subset of host pathways was targeted so as to integrate the glycolytic threshold governing macrophage viability with mechanisms ensuring intracellular bacterial survival. Perturbation of macrophage glycolytic flux was enforced through pathogen-induced enhancement in glucose uptake, which in turn was also influenced by the extracellular glucose concentration. This observation rationalizes the increased susceptibility of diabetic individuals to TB infection Interestingly, Mtb strains also differed in their capacities to stimulate macrophage glucose uptake. Consequently, the resulting pathology is likely dictated both by the individual's glycemic status, and the nature of the infecting strain.


Vyšlo v časopise: Pathogenicity of Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004265
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004265

Souhrn

Mycobacterium tuberculosis (Mtb) is a highly successful human pathogen, representing the leading bacterial cause of death worldwide. Mtb infects macrophages and it adapts to the hostile intracellular milieu of this cell by exploiting the plasticity of its central carbon metabolism machinery. While several studies have detailed the bacterial adaptations that accompany infection, it is still unclear whether this process also involves engagement with host metabolic pathways. We therefore profiled the kinetic flux of host cell metabolites in macrophages that were infected with differently virulent Mtb strains. Interestingly, we found that Mtb pathogenicity was indeed intimately linked to its capacity to regulate host cell metabolism. A unique subset of host pathways was targeted so as to integrate the glycolytic threshold governing macrophage viability with mechanisms ensuring intracellular bacterial survival. Perturbation of macrophage glycolytic flux was enforced through pathogen-induced enhancement in glucose uptake, which in turn was also influenced by the extracellular glucose concentration. This observation rationalizes the increased susceptibility of diabetic individuals to TB infection Interestingly, Mtb strains also differed in their capacities to stimulate macrophage glucose uptake. Consequently, the resulting pathology is likely dictated both by the individual's glycemic status, and the nature of the infecting strain.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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