Transport of outer membrane lipids in mycobacteria

Touchette, Megan H.; Seeliger, Jessica C.

doi:10.1016/j.bbalip.2017.01.005

Cited by 27 publications

(26 citation statements)

References 128 publications

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“…One of the remarkable features of mycobacteria is their unusually complex cell envelope. In contrast to most Gram-positive bacteria, mycobacteria are surrounded by a lipid-rich envelope that contains an outer (myco)membrane composed of mycolic acid-lipids (27,28). Thus, their cell wall structure more closely resembles those of Gram-negative diderms, and it is thought to constitute an additional barrier against antimycobacterial agents (29).…”

Section: Discussionmentioning

confidence: 99%

Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis

Clark

Judd

Lasek‐Nesselquist

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Conjugal cell-cell contact between strains of induces the transcript, which encodes the putative primary substrates of the ESAT-6 secretion system 4 (ESX-4) secretion system. This recipient response was required for conjugal transfer of chromosomal DNA from the donor strain. Here we show that the extracytoplasmic σ factor, SigM, is a cell contact-dependent activator of ESX-4 expression and is required for conjugal transfer of DNA in the recipient strain. The SigM regulon includes genes outside the seven-gene core locus that we show are also required for conjugation, and we show that some of these SigM-induced proteins likely function through ESX-4. A fluorescent reporter revealed that SigM is specifically activated in recipient cells in direct contact with donor cells. Coculture RNA-seq experiments indicated that SigM regulon induction occurred early and before transconjugants are detected. This work supports a model wherein donor contact with the recipient cell surface inactivates the transmembrane anti-SigM, thereby releasing SigM. Free SigM induces an extended ESX-4 secretion system, resulting in changes that facilitate chromosomal transfer. The contact-dependent inactivation of an extracytoplasmic σ-factor that tightly controls ESX-4 activity suggests a mechanism dedicated to detect, and appropriately respond to, external stimuli from mycobacteria.

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Section: Discussionmentioning

confidence: 99%

Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis

Clark

Judd

Lasek‐Nesselquist

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…MmpL3 transports trehalose monomycolate (TMM), which serves as a mycolate donor in the formation of the arabinogalactan-linked mycolates (AGM) and the free lipid TDM 7–9 . Homologues of LppX, which make up the lipid-binding lipoprotein or Llp family 10 , have been shown to bind various lipids in vitro , which suggests analogous roles in lipid localization 11–12 . Indeed, the homologue LprG is required for the surface display of LAM, a triacylated lipoglycan 13–14 .…”

Section: Introductionmentioning

confidence: 99%

A Screen for Protein–Protein Interactions in Live Mycobacteria Reveals a Functional Link between the Virulence-Associated Lipid Transporter LprG and the Mycolyltransferase Antigen 85A

et al. 2017

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Outer membrane lipids in pathogenic mycobacteria are important for virulence and survival. While biosynthesis of these lipids has been extensively studied, mechanisms responsible for their assembly in the outer membrane are not understood. In the study of Gram-negative outer membrane assembly, protein-protein interactions define transport mechanisms, but analogous interactions have not been explored in mycobacteria. Here we identified interactions with the lipid transport protein LprG. Using site-specific photocrosslinking in live mycobacteria, we mapped three major interaction interfaces within LprG. We went on to identify proteins that crosslink at the entrance to the lipid binding pocket, an area likely relevant to LprG transport function. We verified LprG site-specific interactions with two hits, the conserved lipoproteins LppK and LppI. We further showed that LprG interacts physically and functionally with the mycolyltransferase Ag85A, as loss of either protein leads to similar defects in cell growth and mycolylation. Overall, our results support a model in which protein interactions coordinate multiple pathways in outer membrane biogenesis and connect lipid biosynthesis to transport.

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“…The watersoluble cMBT is released into the environment, where it retrieves Fe 3 + ions in soluble form or, in case of pathogenic mycobacteria, from iron-containing host proteins such as transferrin or lactoferrin (Sritharan, 2016;Chao et al, 2019). The lipophilic MBT localises to mycobacterial membranes and the cell wall and remains membrane/ cell wall-bound (Ratledge, Patel, & Mundy, 1982;Touchette & Seeliger, 2017), but can also be released in membrane vesicles (MVs) and thus might bind Fe 3+ beyond the immediate vicinity of the bacteria (Gupta & Rodriguez, 2018;Prados-Rosales et al, 2014).…”

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confidence: 99%

Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes

Knobloch

Koliwer‐Brandl

Arnold

et al. 2020

Cellular Microbiology

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Mycobacterium marinum is a model organism for pathogenic Mycobacterium species, including Mycobacterium tuberculosis, the causative agent of tuberculosis. These pathogens enter phagocytes and replicate within the Mycobacterium‐containing vacuole, possibly followed by vacuole exit and growth in the host cell cytosol. Mycobacteria release siderophores called mycobactins to scavenge iron, an essential yet poorly soluble and available micronutrient. To investigate the role of M. marinum mycobactins, we purified by organic solvent extraction and identified by mass spectrometry the lipid‐bound mycobactin (MBT) and the water‐soluble variant carboxymycobactin (cMBT). Moreover, we generated by specialised phage transduction a defined M. marinum ΔmbtB deletion mutant predicted to be defective for mycobactin production. The M. marinum ΔmbtB mutant strain showed a severe growth defect in broth and phagocytes, which was partially complemented by supplying the mbtB gene on a plasmid. Furthermore, purified Fe‐MBT or Fe‐cMBT improved the growth of wild type as well as ΔmbtB mutant bacteria on minimal plates, but only Fe‐cMBT promoted the growth of wild‐type M. marinum during phagocyte infection. Finally, the intracellular growth of M. marinum ΔmbtB in Acanthamoeba castellanii amoebae was restored by coinfection with wild‐type bacteria. Our study identifies and characterises the M. marinum MBT and cMBT siderophores and reveals the requirement of mycobactins for extra‐ and intracellular growth of the pathogen.

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Transport of outer membrane lipids in mycobacteria

Cited by 27 publications

References 128 publications

Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis

Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis

A Screen for Protein–Protein Interactions in Live Mycobacteria Reveals a Functional Link between the Virulence-Associated Lipid Transporter LprG and the Mycolyltransferase Antigen 85A

Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes

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