Fig 1.
The major components of the M. abscessus cell envelope.
The MOM displays morphologically and immunologically important lipid moieties such as GPLs, TDMs, TMMs, PIMs and TPPs. The CM displays membrane embedded protein assemblies that are essential for the transport of these lipids as well as for the release of virulence factors. These include 3 major complexes: (1) MmpL4-MmpS-GAP, which aid in the transport of GPLs to the outer surface of M. abscessus and regulate the smooth to rough morphotype transition; (2) MmpLs, implicated in drug efflux mechanisms; and (3) ESX-3 and ESX-4, implicated in infecting host cells through the release of the effector molecules EsxG/H and EsxT/U, respectively. CM, cytoplasmic membrane; GPL, glycopeptidolipid; MmpL, Mycobacterial membrane proteins Large; MOM, mycolic acid outer membrane; PIM, phosphatidyl-myo-inositol dimannoside; TDM, trehalose-6,6-dimycolate; TMM, trehalose monomycolate; TPP, trehalose polyphleate.
Fig 2.
Colony morphotypes in M. abscessus.
(A) Smooth colony morphotype, exemplified by the round colony edges, and (B) rough colony morphotype, characterized by the irregular edges and flat surface. Freezer stocks of M. abscessus ATCC 19977 were first used to inoculate liquid Middlebrook 7H9 media supplemented with 0.05% Tween-80, 0.2% glycerol, and OADC and grown at 37°C until mid-log phase (OD600 of 0.6–0.7). Cultures were then plated on Middlebrook 7H10 solid media supplemented with 0.2% glycerol and OADC for 5–7 days at 37°C. Scale bar, 3 mm.
Fig 3.
Gene clusters for ESX-3 and ESX-4 in M. abscessus compared to M. tuberculosis.
Both ESX-3 and ESX-4 encode for major structural components as well as secreted substrates. The genes eccB, eccC, eccD, eccE, and mycP encode for proteins that make up the intact machinery of the ESX systems. ESX substrate molecules include PE5-PPE4, EsxG, and EsxH for ESX-3, and EsxT and EsxU for ESX-4.
Fig 4.
Single-particle cryo-EM structure of the core complex of ESX-5 from M. tuberculosis.
The core complex is composed of EccB, EccC, EccD, EccE, and MycP and spans the CM. Top and bottom views of the complex reveal the multimeric nature of the complex with its dimensions.
Fig 5.
Proposed effects of ESX-3 and ESX-4 in M. abscessus on CFTR-defective phagocytes.
M. abscessus as an NTM known to exacerbate prerespiratory conditions such as CF through mechanism that are not yet well characterized. The effects of ESX-3 and ESX-4 may overlap with the pathophysiology of a dysfunctional CFTR protein and worsen disease states.