Metabolism of Plasma Membrane Lipids in Mycobacteria and Corynebacteria

Crellin, Paul K.; Luo, Chu-Yuan; Morita, Yoshiko

doi:10.5772/52781

Cited by 7 publications

(10 citation statements)

References 186 publications

(207 reference statements)

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“…Apart from inherent SCE stress, the negatively charged head groups present on the LD phospholipid monolayer are also known to mediate interactions with PspA and Vipp1 (23,24). As the phospholipid monolayer of bacterial LDs is thought to be derived from the plasma membrane, the M. smegmatis LD phospholipid monolayer is expected to contain several negatively charged lipid species, including phosphatidic acid, phosphatidylserine, phosphatidylglycerol, cardiolipin, and various phosphatidylinositol species (50)(51)(52). Thus, the presence of anionic phospholipids and the general lipid packing defects present within the phospholipid monolayer may regulate the localization of PspA family members to LDs.…”

Section: Discussionmentioning

confidence: 99%

Association of Mycobacterium Proteins with Lipid Droplets

et al. 2018

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is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in In particular, the loss or overproduction of PspA alters LD homeostasis in and attenuates the survival of during nonreplicating persistence. Here, PspA (PspA) and a Δ mutant were used as model systems to investigate the mechanism by which PspA associates with LDs and determine if other proteins associate with LDs using a mechanism similar to that for PspA. Through this work, we established that the amphipathic helix present in the first α-helical domain (H1) of PspA is both necessary and sufficient for the targeting of this protein to LDs. Furthermore, we identified other proteins that also possess amphipathic helices similar to PspA H1, including a subset that localize to LDs. Altogether, our results indicate that amphipathic helices may be an important mechanism by which proteins target LDs in prokaryotes. spp. are one of the few prokaryotes known to produce lipid droplets (LDs), and their production has been linked to aspects of persistent infection by Unfortunately, little is known about LD production in these organisms, including how LDs are formed, their function, or the identity of proteins that associate with them. In this study, an established LD protein and a surrogate host were used as model systems to study the interactions between proteins and LDs in bacteria. Through these studies, we identified a commonly occurring protein motif that is able to facilitate the association of proteins to LDs in prokaryotes.

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Section: Discussionmentioning

confidence: 99%

Association of Mycobacterium Proteins with Lipid Droplets

et al. 2018

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“…MTB use triacylglycerides (TG) as a major storage lipid. Interestingly, inside macrophages MTB accumulates TG using FAs secreted from host TG and this approach is vital for obtaining a dormancy characteristic (Paul et al 2013). Remarkably, TG accumulates in MTB as they cease growth in response to stress.…”

Section: Iron Restriction Leads To Increased Metabolic Flux Towards Fa and Tg Synthesismentioning

confidence: 99%

Understanding lipidomic basis of iron limitation induced chemosensitization of drug-resistant Mycobacterium tuberculosis

et al. 2019

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Under limited micronutrients condition, Mycobacterium tuberculosis (MTB) has to struggle for acquisition of the limited micronutrients available in the host. One such crucial micronutrient that MTB requires for the growth and sustenance is iron. The present study aimed to sequester the iron supply of MTB to control drug resistance in MTB. We found that iron restriction renders hypersensitivity to multidrug-resistant MTB strains against first-line anti-TB drugs. To decipher the effect of iron restriction on possible mechanisms of chemosensitization and altered cellular circuitry governing drug resistance and virulence of MTB, we explored MTB cellular architecture. We could identify non-intact cell envelope, tampered MTB morphology and diminished mycolic acid under iron restricted MDR-MTB cells. Deeper exploration unraveled altered lipidome profile observed through conventional TLC and advanced mass spectrometry-based LC-ESI-MS techniques. Lipidome analysis not only depicted profound alterations of various lipid classes which are crucial for pathogenecity but also exposed leads such as indispensability of iron to sustain metabolic, genotoxic and oxidative stresses. Furthermore, iron deprivation led to inhibited biofilm formation and capacity of MTB to adhere buccal epithelial cells. Lastly, we demonstrated enhanced survival of Mycobacterium-infected Caenorhabditis elegans model under iron limitation. The present study offers evidence and proposes alteration of lipidome profile and affected virulence traits upon iron chelation. Taken together, iron deprivation could be a potential strategy to rescue MDR and enhance the effectiveness of existing anti-TB drugs. Keywords Myocbacterium • Iron • Lipids • Membrane • Lipidomics • Glyoxylate cycle • Biofilm Abbreviations MTB Mycobacterium tuberculosis MDR Multidrug resistance ADC Albumin dextrose catalase OADC Oleic albumin dextrose catalase 2,4 DNP 2,4 dinitrophenol CFW Calcoflour white CV Crystal violet Electronic supplementary material The online version of this article (

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“…Con A can bind to the carbohydrate based structures on the surface of BCG-mCherry such as mannose. Mannose is present in the form of mannose-capped lipoarabinomannan (Man-LAM) and is accessible for specific interactions with Con A [26].…”

Section: Fluorescence Microscopymentioning

confidence: 99%

Polymer-coated magnetic nanoparticles for the efficient capture of Mycobacterium tuberculosis (Mtb)

Smit

Lutz

2020

SN Appl. Sci.

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Modified chitosan and modified poly(styrene-alt-maleic anhydride) (SMA) were synthesized and utilized to coat superparamagnetic magnetite nanoparticles (SPMNs) to act as potential Mycobacterium tuberculosis (Mtb) capturing substrates. Chitosan and SMA were modified to form quaternary derivatives which have the potential to interact with the Mtb cell wall. The nano-substrates were also surface functionalized with a carbohydrate-binding protein, namely Concanavalin A (Con A), which can bind to the Mtb cell wall. Chitosan coated SPMNs were synthesized by in situ co-precipitating Fe 2+ and Fe 3+ with chitosan followed by further modification. SMA coated SPMNs were synthesized by activating the iron oxide core with 3-aminopropyl(triethoxysilane) followed by further modification. The nano-substrates were evaluated for their affinity and thus capturing capabilities utilizing the mCherry fluorophore tagged bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, a live attenuated Mtb-mimic. Quaternary SMA (SMI-qC 12 ) revealed the highest overall affinity for BCG-mCherry (through electrostatic and hydrophobic interactions) whereas Con A immobilized chitosan had the highest affinity for the chitosan coated nanoparticles. The SPMNs were coated with three different polymer loadings and a dilution study was performed to determine the limit of detection. The 0.9 g loaded SMI-qC 12 SPMNs revealed the highest affinity for BCG-mCherry as determined via fluorescence microscopy and transmission electron microscopy.

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Metabolism of Plasma Membrane Lipids in Mycobacteria and Corynebacteria

Cited by 7 publications

References 186 publications

Association of Mycobacterium Proteins with Lipid Droplets

Association of Mycobacterium Proteins with Lipid Droplets

Understanding lipidomic basis of iron limitation induced chemosensitization of drug-resistant Mycobacterium tuberculosis

Polymer-coated magnetic nanoparticles for the efficient capture of Mycobacterium tuberculosis (Mtb)

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