The role of hydrophobicity in tuberculosis evolution and pathogenicity

Monika Jankute,Michael R Barer,Oona Y -C Lee,Apoorva Bhatt,David E Minnikin,Malin Ridell,Houdini H T Wu,Vijayashankar Nataraj,Gurdyal S Besra,Natalie J Garton

doi:10.1038/s41598-017-01501-0

Monika Jankute, Michael R Barer + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-01501-0

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Abstract

The evolution of tubercle bacilli parallels a route from environmental Mycobacterium kansasii, through intermediate “Mycobacterium canettii”, to the modern Mycobacterium tuberculosis complex. Cell envelope outer membrane lipids change systematically from hydrophilic lipooligosaccharides and phenolic glycolipids to hydrophobic phthiocerol dimycocerosates, di- and pentaacyl trehaloses and sulfoglycolipids. Such lipid changes point to a hydrophobic phenotype for M. tuberculosis sensu stricto. Using Congo Red staining and hexadecane-aqueous buffer partitioning, the hydrophobicity of rough morphology M. tuberculosis and Mycobacterium bovis strains was greater than smooth “M. canettii” and M. kansasii. Killed mycobacteria maintained differential hydrophobicity but defatted cells were similar, indicating that outer membrane lipids govern overall hydrophobicity. A rough M. tuberculosis H37Rv ΔpapA1 sulfoglycolipid-deficient mutant had significantly diminished Congo Red uptake though hexadecane-aqueous buffer partitioning was similar to H37Rv. An M. kansasii, ΔMKAN27435 partially lipooligosaccharide-deficient mutant absorbed marginally more Congo Red dye than the parent strain but was comparable in partition experiments. In evolving from ancestral mycobacteria, related to “M. canettii” and M. kansasii, modern M. tuberculosis probably became more hydrophobic by increasing the proportion of less polar lipids in the outer membrane. Importantly, such a change would enhance the capability for aerosol transmission, affecting virulence and pathogenicity.

Highlights

Coherent explanations are required for the development and upsurge in tuberculosis (TB) during the recent Holocene epoch
It was realised that this selection of M. tuberculosis mycobacterial outer membrane (MOM) free lipids (PDIMs, SGLs and Diacyl trehaloses (DATs) and pentaacyl trehaloses (PATs)) was markedly apolar in comparison with those found in M. kansasii and “M. canettii” and this might result in relatively increased hydrophobicity of the cell surface[3]
The extractable free lipid compositions of the cultures examined are summarised in Table 1 and two-dimensional thin-layer chromatographic (2D TLC) patterns are displayed in Supplementary Figs S1–S3

Summary

Introduction

Coherent explanations are required for the development and upsurge in tuberculosis (TB) during the recent Holocene epoch. Assuming a working hypothesis, involving an evolutionary progression from M. kansasii-like mycobacteria to M. tuberculosis via ancient relatives of “M. canettii”, it is possible to envisage a coherent developing pattern of mycobacterial outer membrane lipid changes (Fig. 1)[2, 3]. On proceeding from “M. canettii” to M. tuberculosis sensu stricto, DATs, PATs, PDIMs are maintained, sulfoglycolipids (SGLs) are expressed, but PGLs and LOSs are deleted The outcome of these changes is that M. tuberculosis sensu stricto has rather simplified mycobacterial outer membrane (MOM) free lipids, comprising only PDIMs, SGLs and DATs and PATs (Fig. 1). It was realised that this selection of M. tuberculosis MOM free lipids (PDIMs, SGLs and DATs and PATs) was markedly apolar in comparison with those found in M. kansasii and “M. canettii” and this might result in relatively increased hydrophobicity of the cell surface[3]. Available M. tuberculosis and M. kansasii mutants lacking SGLs and higher subclasses of LOSs, respectively[18, 19], were used to investigate possible involvement of these lipids in cell-surface variation and hydrophobicity

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