2017
DOI: 10.3389/fcimb.2017.00388
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Controlling Extra- and Intramacrophagic Mycobacterium abscessus by Targeting Mycolic Acid Transport

Abstract: Mycobacterium abscessus is a rapidly growing mycobacterium (RGM) causing serious infections especially among cystic fibrosis patients. Extremely limited therapeutic options against M. abscessus and a rise in infections with this mycobacterium require novel chemotherapies and a better understanding of how the bacterium causes infection. Different from most RGM, M. abscessus can survive inside macrophages and persist for long durations in infected tissues. We recently delineated differences in the infective prog… Show more

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Cited by 21 publications
(22 citation statements)
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“…New approaches to combat M. abscessus infections may rely on the discovery of completely new chemical entities that inhibit essential pathways in this bacterium (Viljoen et al, 2017 ). This may involve the improvement of available compounds to better inhibit putative molecular targets in M. abscessus , which may have slightly different structures or functions compared to orthologs efficiently inhibited in other bacteria.…”
Section: Introductionmentioning
confidence: 99%
“…New approaches to combat M. abscessus infections may rely on the discovery of completely new chemical entities that inhibit essential pathways in this bacterium (Viljoen et al, 2017 ). This may involve the improvement of available compounds to better inhibit putative molecular targets in M. abscessus , which may have slightly different structures or functions compared to orthologs efficiently inhibited in other bacteria.…”
Section: Introductionmentioning
confidence: 99%
“…Our main finding is that loss of GPLs during the S-to-R switch leads to major changes in nanoscale surface hydrophobicity, without any apparent change in cell surface ultrastructure. Despite the multiple phenotypic differences previously associated with this morphological transition, 14,22 we found it remarkable that both variants exhibit the same uniform, featureless nanoscale surface architecture, indicating that GPLs are not major determinants of cell shape and surface topology in M. abscessus. In an earlier study on M. abscessus morphology, scanning electron micrographs showed similar featureless surfaces of M. abscessus S and R variants, while dramatic differences in communal bacterial organization were clear in lower magnification micrographs.…”
Section: Discussionmentioning
confidence: 49%
“…This conclusion is supported by (i) the intrinsic extreme hydrophobicity of mycolic acids and (ii) the fact that apramycin, an unrelated drug that affects protein synthesis in general, also increases surface roughness of both S and R variants, yet had no clear effects on surface hydrophobicity. That BM212-treatment significantly decreased the distribution and strength of hydrophobic adhesive forces on M. abscessus proves that the inhibitors of MmpL3 22,42 show promise as chemotherapeutic measures to interfere with the highly hydrophobic nature of the mycobacterial cell wall.…”
Section: Discussionmentioning
confidence: 93%
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“…Complex lipids thought to be transported by MmpL proteins include PDIM (MmpL7), sulfoglycolipid (MmpL8), diacyltrehaloses (DATs) and polyacyltrehaloses (MmpL10), monomeromycolyl diacylglycerol (MmpL11), and trehalose monomycolate (MmpL3), all of which have been implicated in M. tuberculosis virulence (31,32). Additionally, the essential MmpL3 transporter represents a promising pharmacological target in M. tuberculosis and M. abscessus (33)(34)(35). In M. abscessus, we and others unraveled the specific role of MmpL4a and MmpL4b in GPL transport by analyzing the S to R transition in the three subspecies of the M. abscessus complex (17,22,36).…”
Section: Significancementioning
confidence: 99%