Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function.

Scientific Reports
Ankur BothraVivek Rao

Abstract

The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculosis MmpL11 in the maintenance of the cell wall architecture and stability in response to surface stress. In the presence of a detergent like Tyloxapol, a mmpL11 deletion mutant suffered from a severe growth attenuation as a result of altered membrane polarity, permeability and severe architectural damages. This mutant failed to tolerate permissible concentrations of cis-fatty acids suggesting its increased sensitivity to surface stress, evident as smaller colonies of the mutant outgrown from lipid rich macrophage cultures. Additionally, loss of MmpL11 led to an altered cellular fatty acid flux in the mutant: reduced incorporation into membrane cardiolipin was associated with an increased flux into the cellular triglyceride pool. This increase in storage lipids like triacyl glycerol (TAG) was associated with the altered metabolic state of higher dormancy-associated gene expression and decreased sensitivity to frontline TB drugs. This s...Continue Reading

References

Jan 9, 1999·Clinical Microbiology Reviews·G McDonnell, A D Russell
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Scott E ConverseJeffery S Cox
Nov 1, 2003·The Journal of Infectious Diseases·Peter SeilerPeter Aichele
Feb 6, 2004·Journal of Bacteriology·Riccardo ManganelliIssar Smith
May 24, 2005·Infection and Immunity·Pilar DomenechClifton E Barry
Sep 14, 2007·Immunological Reviews·William R Berrington, Thomas R Hawn
Mar 1, 2008·Applied Microbiology and Biotechnology·K CôtesS Canaan
Sep 5, 2008·Current Protocols in Microbiology·Catherine Vilchèze, William R Jacobs
Aug 10, 2010·Microbes and Infection·Christina L Stallings, Michael S Glickman
Nov 26, 2010·Molecular Microbiology·Lanbo ShiMaria L Gennaro
Jul 8, 2011·Frontiers in Microbiology·Martin I VoskuilGary K Schoolnik
Nov 19, 2011·ACS Medicinal Chemistry Letters·Luiz Pedro S de CarvalhoCarl Nathan
Apr 24, 2012·Chemistry & Biology·Cristian VarelaApoorva Bhatt
Jan 26, 2013·Journal of Separation Science·Alexander FaulandErnst Lankmayr
Dec 24, 2013·Mediterranean Journal of Hematology and Infectious Diseases·Lanfranco FattoriniFederico Giannoni
Feb 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Christopher M JonesMichael Niederweis
Jul 11, 2014·PloS One·Koen AndriesAnil Koul
Aug 16, 2014·The Journal of Biological Chemistry·Juan Manuel BelardinelliMary Jackson
Jul 3, 2015·Cellular Microbiology·Thomas R LernerMaximiliano G Gutierrez
Oct 22, 2015·Annual Review of Microbiology·Monika JankuteGurdyal S Besra
Dec 3, 2015·Chemistry & Biology·Sonali SrivastavaRajesh S Gokhale
Dec 30, 2015·Molecular Microbiology·R Székely, S T Cole
Dec 16, 2016·Parasitology·Katherine A Abrahams, Gurdyal S Besra
Jan 28, 2017·PLoS Genetics·Godefroid CharbonAnders Løbner-Olesen

❮ Previous
Next ❯

Methods Mentioned

BETA
PMA
PCR
FACS
Transmission electron microscopy
fluorescence microscopy

Software Mentioned

VOLOCITY

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.