Publications

The immunomodulatory potential of mycobacteria to be used for therapeutic purposes varies by species and culture conditions and is closely related to mycobacterial lipid composition. Although the lipids present in the mycobacterial cell wall are relevant, lipids are mainly stored in intracellular lipid inclusions (ILIs), which have emerged as a crucial structure in understanding mycobacteria-host interaction. Little is known about ILI ultrastructure, production, and composition in nonpathogenic species. In this study, we compared the lipid profiles of the nonpathogenic immunomodulatory agent Mycobacterium brumae during pellicle maturation under different culture conditions with qualitative and quantitative approaches by using high-resolution imaging and biochemical and composition analyses to understand ILI dynamics. The results showed wax esters, mainly in early stages of development, and acylglycerols in mature ILI composition, revealing changes in dynamics, amount, and morphometry, depending on pellicle maturation and the culture media used. Low-glycerol cultures induced ILIs with lower molecular weights which were smaller in size in comparison with the ILIs produced in glycerol-enriched media. The data also indicate the simple metabolic plasticity of lipid synthesis in M. brumae, as well as its high versatility in generating different lipid profiles. These findings provide an interesting way to enhance the production of key lipid structures via the simple modulation of cell culture conditions.

JTD Keywords: cell wall, electron microscopy, intrabacterial, lipid inclusions, mycobacterium, Bodies, Cell wall, Electron microscopy, Growth, In-vitro, Intrabacterial, Lipid inclusions, Mycobacterium, Prokaryotes, Triacylglycerol, Tuberculosis, Ultrastructural imaging, Virulence, Wax esters

Within the research in Molecular Biology, one important field along the years has been the analyses on how prokaryotes regulate the expression of their genes and what the consequences of these activities are. Prokaryotes have attracted the interests of researchers not only because the processes taking place in their world are important to cells, but also because many of the effects often can be readily measured, both at the single cell level and in large populations. Contributing to the interest of the present topic is the fact that modulation of gene activity involves the sensing of intra- and inter-cellular conditions, DNA binding and DNA dynamics, and interaction with the replication/transcription machinery of the cell. All of these processes are fundamental to the operation of a biological entity and they condition its lifestyle. Further, the discoveries achieved in the bacterial world have been of ample use in eukaryotes. In addition to the fundamental interest of understanding modulation of prokaryotic lifestyle by DNA-binding proteins, there is an added interest from the healthcare point of view. As it is well-known the antibiotic-resistance strains of pathogenic bacteria are a major world problem, so that there is an urgent need of innovative approaches to tackle it. Human and animal infectious diseases impose staggering costs worldwide in terms of loss of human life and livestock, diminished productivity, and the heavy economic burden of disease. The global dimension of international trade, personal travel, and population migration expands at an ever-accelerating rate. This increasing mobility results in broader and quicker dissemination of bacterial pathogens and in rapid spread of antibiotic resistance. The majority of the newly acquired resistances are horizontally spread among bacteria of the same or different species by processes of lateral (horizontal) gene transfer, so that discovery of new antibiotics is not the definitive solution to fighting infectious diseases. There is an absolute need of finding novel alternatives to the “classical” approach to treat infections by bacterial pathogens, and these new ways must include the exploration and introduction of novel antibacterials, the development of alternative strategies, and the finding of novel bacterial targets. However, all these approaches will result in a stalemate if we, researchers, are not able to achieve a better understanding of the mechanistic processes underlying bacterial gene expression. It is, then, imperative to continue gaining insight into the basic mechanisms by which bacterial cells regulate the expression of their genes. That is why our Research Topic hosted by Frontiers in Molecular Biosciences was timely, and the output of it offers novel and up-to-date points of view to the “simple” bacterial world.

JTD Keywords: DNA-protein interactions, Gene regulation in Prokaryotes, Replication control, Regulation of Bacterial Gene Expression, Global Regulatory Networks