Association of Mycobacterium Proteins with Lipid Droplets

Armstrong, Richard M.; Carter, Dominique C.; Atkinson, Samantha N; Terhune, Scott S.; Zahrt, Thomas C.

doi:10.1128/jb.00240-18

Cited by 16 publications

(37 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The proteomic study revealed that PspA was also one of the LD major proteins same as other bacteria, suggesting that the E coli TOP10 has the ability to form LDs and the LDs are conserved in Bacteria domain. Additionally, a recent study reports that PspA targets bacterial LDs using an amphipathic α-helix [50], which is similar with the pattern of mammalian LD protein localization [6]. Furthermore, current study also found that PspA was conserved from bacteria, archaea, to eukaryotes (Fig.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

Lipid Droplet Is an Ancient and Inheritable Organelle in Bacteria

Chi

Ogunsade

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Lipid droplet (LD) is a monolayer phospholipid membrane-bound organelle found in all eukaryotes and several prokaryotes which plays key roles in cellular lipid homeostasis and human health. The origin and evolution of the organelle remains unknown. Here, we report that through screening over 660 bacteria using biophysical and biochemical methods, plus LD isolation and proteomic tool, LDs were identified in most of these microbes, affiliated with five main bacterial phyla. Moreover, LDs were also identified in E. coli overexpressing lipid synthesis enzymes, indicating that bacteria without detectable LDs possessed the ability of LD biogenesis. The similarity of isolated LDs from representative strains and evolutionary analysis of LD major protein PspA demonstrate that LDs were conserved in bacteria. Furthermore, time-lapse imaging revealed that LDs were inheritable accompanying with bacterial growth and division. Finally, a common ancestor of LD-containing bacteria was predicted to originate 3.19 billion years ago by a phylogenetic analysis. Our findings suggest that LD is a widespread and inheritable organelle from an ancient common ancestor.

show abstract

Section: Discussionsupporting

confidence: 80%

“…PspA from E. coli can localize on the LDs in Mycobacterium smegmatis [50]. These results suggest that PspA is not only a widespread protein existing in Bacteria domain, but also a universal LD protein in bacteria.…”

Section: The Lipid Droplets Are Conserved and Inheritable In Bacteriamentioning

confidence: 77%

Lipid Droplet Is an Ancient and Inheritable Organelle in Bacteria

Chi

Ogunsade

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In phenotype A, bright red fluorescence was found within the compartments surrounded by EGFP-HBHA ( Figure 2D ), indicating that these structures could correspond to ILI for TAG storage. This second localization is supported by the recent description of M. smegmatis HBHA homolog (MSMEG_0919) as a major protein associated with ILI by proteomic analysis of isolated ILI ( Armstrong et al, 2018 ).…”

Section: Resultsmentioning

confidence: 55%

“…Our data do not support this hypothesis and show that, in addition to its adhesin properties, HBHA has conserved a role in ILI accumulation and maturation. Recently, the M. smegmatis HBHA homolog (MSMEG_0919) has been found as the major ILI-associated protein ( Armstrong et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Heparin-Binding Hemagglutinin Adhesin (HBHA) Is Involved in Intracytosolic Lipid Inclusions Formation in Mycobacteria

et al. 2018

View full text Add to dashboard Cite

The heparin-binding hemagglutinin adhesin (HBHA) is an important virulence factor of Mycobacterium tuberculosis. It is a surface-displayed protein that serves as an adhesin for non-phagocytic cells and is involved in extra-pulmonary dissemination of the tubercle bacillus. It is also an important latency antigen useful for the diagnosis of latently M. tuberculosis-infected individuals. Using fluorescence time-lapse microscopy on mycobacteria that produce HBHA-green fluorescent protein chimera, we show here that HBHA can be found at two different locations and dynamically alternates between the mycobacterial surface and the interior of the cell, where it participates in the formation of intracytosolic lipid inclusions (ILI). Compared to HBHA-producing mycobacteria, HBHA-deficient mutants contain significantly lower amounts of ILI when grown in vitro or within macrophages, and the sizes of their ILI are significantly smaller. Lipid-binding assays indicate that HBHA is able to specifically bind to phosphatidylinositol and in particular to 4,5 di-phosphorylated phosphatidylinositol, but not to neutral lipids, the main constituents of ILI. HBHA derivatives lacking the C-terminal methylated, lysine-rich repeat region fail to bind to these lipids and these derivatives also fail to complement the phenotype of HBHA-deficient mutants. These studies indicate that HBHA is a moonlighting protein that serves several functions depending on its location. When surface exposed, HBHA serves as an adhesin, and when intracellularly localized, it participates in the generation of ILI, possibly as a cargo to transport phospholipids from the plasma membrane to the ILI in the process of being formed.

show abstract

“…One of the additional upregulated genes in hbhR::Tn is pspA . Recent proteomic analyses of ILI‐associated proteins in M. smegmatis showed that PspA and HBHA are the two most abundant proteins (Armstrong et al , ), suggesting that co‐regulation of these genes is paralleled with similar function of their gene products. Carbon storage is an important trait of M. tuberculosis to reach a dormant state.…”

Section: Discussionmentioning

confidence: 99%

Coordinate regulation of virulence and metabolic genes by the transcription factor HbhR in Mycobacterium marinum

Raze

Segers

Mille

et al. 2019

Molecular Microbiology

View full text Add to dashboard Cite

The heparin-binding hemagglutinin (HBHA) is a multifunctional protein involved in adherence ofMycobacterium tuberculosis to non-phagocytic cells and in the formation of intracytosolic lipid inclusions. We demonstrate that the expression of hbhA is regulated by a transcriptional repressor, named HbhR, in Mycobacterium marinum. The hbhR gene, located upstream of hbhA, was identified by screening a transposon insertion library and detailed analysis of a mutant overproducing HBHA. HbhR was found to repress both hbhA and hbhR transcription by binding to the promoter regions of both genes. Complementation restored production of HBHA. RNA-seq analyses comparing the mutant and parental strains uncovered 27 genes, including hbhA, that were repressed and 20 genes activated by HbhR. Among the former, the entire locus of genes coding for a type-VII secretion system, including esxA, esxB and pe-ppe paralogs, as well as the gene coding for PspA, present in intracellular lipid vesicles, was identified, as was katG, a gene involved in the sensitivity to isoniazid. The latter category contains genes that play a role in diverse functions, such as metabolism and resistance to oxidative conditions. Thus, HbhR appears to be a master regulator, linking the transcriptional regulation of virulence, metabolic and antibiotic sensitivity genes in M. marinum. . Transcriptional regulation involved in virulence and metabolism of M. marinum 53

show abstract

Association of Mycobacterium Proteins with Lipid Droplets

Cited by 16 publications

References 61 publications

Lipid Droplet Is an Ancient and Inheritable Organelle in Bacteria

Lipid Droplet Is an Ancient and Inheritable Organelle in Bacteria

Heparin-Binding Hemagglutinin Adhesin (HBHA) Is Involved in Intracytosolic Lipid Inclusions Formation in Mycobacteria

Coordinate regulation of virulence and metabolic genes by the transcription factor HbhR in Mycobacterium marinum

Contact Info

Product

Resources

About