Bacterial lipid bodies: Targeting pathogen fat reserves for infection control

About the Project

Bacterial lipid bodies (LBs), also known as intrabacterial lipid inclusions or lipid droplets, are intracellular accumulations of neutral lipids, such as triacylglycerol (TAG) and wax esters. These are surrounded by a phospholipid monolayer containing proteins that support LB synthesis, structure and degradation. LBs are prevalent in many actinobacteria, including Mycobacterium and Rhodococcus.Whilst many actinobacteria are non-pathogenic inhabitants of the environment, some, for example, members of the Mycobacterium tuberculosis complex (human and bovine tuberculosis (TB)) and Rhodococcus equi (Rattles in foals and infections in other herbivores) are accountable for diseases with significant human and animal health, and socioeconomic impact.

Bacterial LBs have many different roles. LBs are formed in response to stress and have a role in storage of energy and lipid to support metabolism, adaptation and regrowth in more favourable conditions. Mycobacterial LB content is associated with a persister-like state and phenotypic antibiotic tolerance (ineffective antimicrobial killing owing to a microorganism’s metabolic state). Persisters of M. tuberculosis have important impact on TB treatment; they are killed slowly, meaning treatment is lengthy.

We first identified sub-populations of M. tuberculosis with TAG LBs in the sputa of TB patients 1. Such sub-populations revealed during therapy have been associated with treatment failure, or relapse of disease 2. We have recently recognised that M. tuberculosis LB content in sputum, is associated with both the bacterial strain and host response 3 supporting the view that LB content of an M. tuberculosis sputum population may have value as a marker of predictive treatment response.

In vitro, we recognise that some M. tuberculosis strains have significant LB content during growth, indicating that these lipid depots are more dynamic than initially thought. During infection, M. tuberculosis utilises host fatty acids as a source of nutrition and LBs may support this. Furthermore, TAG can be exported outside mycobacterial cell 4, which may result in altered cell envelope composition, changing the biophysical properties of the cell and its interaction with the environment.

In contrast to M. tuberculosis, the LBs of R. equi have not been well-studied. For this soil-resident pathogen, LBs may support environmental survival (as has been observed for other saprophytic Rhodococci 5, but also interaction with the host cell during infection.

There are opportunities for projects concerned with characterisation of the LB biology of R. equi and the role of LBs in environmental survival and host interaction, improving LB assessment and understanding the role of TAG LBs in mycobacterial growth and biophysical properties. Specific projects and hypothesis would be developed with suitable candidates.

Techniques used could include bacterial culture in defined conditions, fluorimetry and cytological assays using fluorescence microscopy and transmission electron microscopy, lipid analytical methods to include thin layer chromatography and mass spectrometry, genetic manipulation of bacteria, transcriptional analyses and cell culture. Training will be provided in all areas.