Dataset Information

Spatial segregation and aging of metabolic processes underlie phenotypic heterogeneity in mycobacteria.

ABSTRACT: Individual cells within clonal populations of mycobacteria vary in size, growth rate, and antibiotic susceptibility. Heterogeneity is, in part, determined by LamA, a protein found exclusively in mycobacteria. LamA localizes to sites of new cell wall synthesis where it recruits proteins important for polar growth and establishing asymmetry. Here, we report that in addition to this function, LamA interacts with complexes involved in oxidative phosphorylation (OXPHOS) at a subcellular location distinct from cell wall synthesis. Importantly, heterogeneity depends on a unique extension of the mycobacterial ATP synthase, and LamA mediates the coupling between ATP production and cell growth in single cells. Strikingly, as single cells age, concentrations of proteins important for oxidative phosphorylation become less abundant, and older cells rely less on oxidative phosphorylation for growth. Together, our data reveal that central metabolism is spatially organized within a single mycobacterium and varies within a genetically identical population of mycobacteria. Designing therapeutic regimens to account for this heterogeneity may help to treat mycobacterial infections faster and more completely.

SUBMITTER: Gwin CM

PROVIDER: S-EPMC10705497 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spatial segregation and aging of metabolic processes underlie phenotypic heterogeneity in mycobacteria.

Gwin Celena M CM Gupta Kuldeepkumar R KR Lu Yao Y Shao Lin L Rego E Hesper EH

bioRxiv : the preprint server for biology 20231202

Individual cells within clonal populations of mycobacteria vary in size, growth rate, and antibiotic susceptibility. Heterogeneity is, in part, determined by LamA, a protein found exclusively in mycobacteria. LamA localizes to sites of new cell wall synthesis where it recruits proteins important for polar growth and establishing asymmetry. Here, we report that in addition to this function, LamA interacts with complexes involved in oxidative phosphorylation (OXPHOS) at a subcellular location dist ...[more]

PMID: 38076906

Similar Datasets

Project description:Although recent studies have shown that human genomes contain hundreds of loci that exhibit signatures of positive selection, variants that are associated with adaptation in energy-balance regulation remain elusive. We reasoned that the difficulty in identifying such variants could be due to heterogeneity in selection pressure and that an integrative approach that incorporated experiment-based evidence and population genetics-based statistical judgments would be needed to reveal important metabolic modifiers in humans.To identify common metabolic modifiers that underlie phenotypic variation in diabetes-associated or obesity-associated traits in humans, or both, we screened 207 candidate loci for regulatory single nucleotide polymorphisms (SNPs) that exhibited evidence of gene-environmental interactions.Three SNPs (rs3895874, rs3848460, and rs937301) at the 5' gene region of human GIP were identified as prime metabolic-modifier candidates at the enteroinsular axis. Functional studies have shown that GIP promoter reporters carrying derived alleles of these three SNPs (haplotype GIP(-1920A)) have significantly lower transcriptional activities than those with ancestral alleles at corresponding positions (haplotype GIP(-1920G)). Consistently, studies of pregnant women who have undergone a screening test for gestational diabetes have shown that patients with a homozygous GIP(-1920A/A) genotype have significantly lower serum concentrations of glucose-dependent insulinotropic polypeptide (GIP) than those carrying an ancestral GIP(-1920G) haplotype. After controlling for a GIPR variation, we showed that serum glucose concentrations of patients carrying GIP(-1920A/A) homozygotes are significantly higher than that of those carrying an ancestral GIP(-1920G) haplotype (odds ratio 3.53).Our proof-of-concept study indicates that common regulatory GIP variants impart a difference in GIP and glucose metabolism. The study also provides a rare example that identified the common variant-common phenotypic variation pattern based on evidence of moderate gene-environmental interactions.

Dataset Information

Spatial segregation and aging of metabolic processes underlie phenotypic heterogeneity in mycobacteria.

Publications

Spatial segregation and aging of metabolic processes underlie phenotypic heterogeneity in mycobacteria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets