The Fur-like regulatory protein MAP3773c modulates key metabolic pathways in Mycobacterium avium subsp. paratuberculosis under in-vitro iron starvation.

Publication date: Apr 18, 2024

Johne’s disease (JD) is a chronic enteric infection of dairy cattle worldwide. Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of JD, is fastidious often requiring eight to sixteen weeks to produce colonies in culture-a major hurdle in the diagnosis and therefore in implementation of optimal JD control measures. A significant gap in knowledge is the comprehensive understanding of the metabolic networks deployed by MAP to regulate iron both in-vitro and in-vivo. The genome of MAP carries MAP3773c, a putative metal regulator, which is absent in all other mycobacteria. The role of MAP3773c in intracellular iron regulation is poorly understood. In the current study, a field isolate (K-10) and an in-frame MAP3773c deletion mutant (ΔMAP3773c) derived from K-10, were exposed to iron starvation for 5, 30, 60, and 90 min and RNA-Seq was performed. A comparison of transcriptional profiles between K-10 and ΔMAP3773c showed 425 differentially expressed genes (DEGs) at 30 min time post-iron restriction. Functional analysis of DEGs in ΔMAP3773c revealed that pantothenate (Pan) biosynthesis, polysaccharide biosynthesis and sugar metabolism genes were downregulated at 30 min post-iron starvation whereas ATP-binding cassette (ABC) type metal transporters, putative siderophore biosynthesis, PPE and PE family genes were upregulated. Pathway analysis revealed that the MAP3773c knockout has an impairment in Pan and Coenzyme A (CoA) biosynthesis pathways suggesting that the absence of those pathways likely affect overall metabolic processes and cellular functions, which have consequences on MAP survival and pathogenesis.

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Concepts Keywords
Atp Avium
Cattle Biosynthesis
Map3773c Iron
Mycobacteria Jd
Starvation Map
Map3773c
Metabolic
Metal
Mycobacterium
Paratuberculosis
Pathways
Putative
Starvation
Subsp

Semantics

Type Source Name
pathway KEGG Metabolic pathways
drug DRUGBANK Iron
disease MESH starvation
disease MESH Johne’s disease
disease MESH infection
drug DRUGBANK Pantothenic acid
pathway REACTOME Metabolism
drug DRUGBANK ATP
drug DRUGBANK Abacavir
drug DRUGBANK Coenzyme A
disease MESH pathogenesis
drug DRUGBANK Coenzyme M
disease MESH malnutrition
drug DRUGBANK ANX-510
disease MESH oxidative stress
drug DRUGBANK Cobalamin
drug DRUGBANK Cyanocobalamin
disease MESH repression
pathway KEGG Homologous recombination
drug DRUGBANK Pidolic Acid
drug DRUGBANK Folic Acid
drug DRUGBANK L-Arginine
drug DRUGBANK Proline
drug DRUGBANK L-Alanine
pathway KEGG Fatty acid biosynthesis
pathway KEGG Lysine biosynthesis
pathway KEGG Pyruvate metabolism
pathway KEGG Polyketide sugar unit biosynthesis
drug DRUGBANK Cholesterol
drug DRUGBANK Zinc
drug DRUGBANK Serine
disease MESH shock
drug DRUGBANK Riboflavin
pathway KEGG Carbon metabolism
disease MESH tuberculosis
pathway KEGG Tuberculosis
pathway KEGG ABC transporters
drug DRUGBANK Nitric Oxide
drug DRUGBANK Oleic Acid
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK L-Asparagine
drug DRUGBANK Glycerin
drug DRUGBANK Magnesium sulfate
drug DRUGBANK Medroxyprogesterone acetate
drug DRUGBANK 7-Methyl-Gpppa
drug DRUGBANK Phosphate ion
drug DRUGBANK Guanidine
drug DRUGBANK Sarcosine
drug DRUGBANK Sodium Citrate
drug DRUGBANK Lysozyme
drug DRUGBANK Silicon
drug DRUGBANK Ethanol
drug DRUGBANK Trimebutine
drug DRUGBANK Methyl isocyanate
pathway KEGG Proteasome
drug DRUGBANK Gold
drug DRUGBANK BCG vaccine

Original Article

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