The subject of this project is a complex aspect of microbial physiology, the interaction between two cellular processes, metal homeostasis and central metabolism. These two processes are usually studied separately, and although obvious, their interaction is little explored in mycobacteria and bacteria more generally.
This project paved the way for understanding the mechanisms of adaptation of highly antibiotic-tolerant bacteria, such as Mycobacterium tuberculosis and Mycobacterium abscessus, to changes in metal availability in different metabolic states.
In this project, it was seen that specific alterations in energy metabolism occur in response to iron deficiency. No specific alterations in central metabolism in response to exposure to sub-inhibitory concentrations of manganese were identified, but alterations related to the translation apparatus were clear.
The nutritional conditions used in this research define a metabolic state of the bacterial cell that has never before been used for antibiotic resistance investigations. Such conditions may provide a new screening platform to identify new drugs or to improve existing therapies, and is applicable to all pathogenic microorganisms, not just mycobacteria. Given the spread of antibiotic resistance, the development of new medicines is urgently needed. And given the functional relevance of metabolism in mediating antibiotic resistance, diversifying screening programmes to test drugs (i.e. compound libraries) on bacteria in differentiated metabolic states defined by two nutrient variants, such as metal ion and carbon source, could represent a valid new way to develop novel antibacterial treatments.
