New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa

Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis

“…Mtb's ICLs catalyse only two known biochemical reactions, both of which use the same active site and play closely related roles in fatty acid metabolism 17 . Recent work reported the discovery of additional roles for ICL in adaptation to hypoxia and nutrient starvation that are unrelated to fatty acid metabolism but relevant to conditions thought to be encountered by Mtb in the host, while another study reported the discovery of a pathway closely interlinked with the glyoxylate shunt also involved in fatty acid metabolism termed the citramalate cycle [34][35][36] . Such evidence has thus begun to suggest that the profoundly attenuating effects of ICL deficiency in Mtb may reflect the loss of multiple physiologic functions, only some of which could be predicted by current genetic, bioinformatic and biochemical approaches.…”

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

“…86 Prof Loots conveyed his optimism of the possibility of using metabolite markers to build diagnostic models based on systematic approaches in metabolomics research. [91][92][93] It could also assist in finding the association between TB and its symptoms; for example, increase epinephrine levels can predict weight loss and insomnia in patients. In the future, this approach could also be used to diagnose drug resistant TB and for prognosis.…”

TB or not TB? Improving the Understanding and Diagnosis of Tuberculosis through Metabolomics

“…Additionally, the direct presence of a pathogen in these samples, or the host's response to the pathogen, would also modify the metabolome. Subsequently, in the context of TB, a number of metabolomics studies have been carried out to date, searching for new markers using patient collected sputum [8,9]. Because of the fact that these altered metabolite markers or metabolite patterns are not only due to the presence of the foreign body in the host, but also due to a specific host response, patient samples carrying little/none of the infectious organism, such as blood [10,11] or urine [12], can also be used for new biomarker identification.…”

“…Apart from their diagnostic applications, various newly identified TB biomarkers have additionally contributed to the existing knowledge of the biology of the causative pathogen [16], as well as to various under lying disease mechanisms [9]. These include mechanisms related to M. tuberculosis drug resistance [16,17] and virulence [18] including upregulation of various antioxidant pathways, the use of alkanes and fatty acids as alternative energy substrates [16,17,19], a shift in aconitase functionality toward mRNA binding and stability [17] and cell "...metabolomics has allowed for better understanding of the adaptations of Mycobacterium tuberculosis to the host's defense and vice versa... " future science group TB or not TB?…”

“…Anti-TB drug mechanisms [20] and side effects in the host have also been elucidated including anti-TB drug inhibition of the host's electron transport chain resulting in oxidative stress and inducing an abnormal organic acid profile [21]. What is of even greater interest, currently, is that metabolomics has allowed for better understanding of the adaptations of M. tuberculosis to the host's defense and vice versa, and subsequently the discovery of the presence of a citramalate cycle in M. tuberculosis, and the interaction of this cycle with an upregulated glyoxylate cycle during infection; an increased utilization of fatty acids and glutamate by M. tuberculosis during infection; an additional mechanism by which the host manufactures hydrogen peroxide in order to eliminate the infecting bacteria; inhibition of the electron transport chain of the host by M. tuberculosis, resulting in elevation in various neurotransmitters and organic acids, better explaining the occurrence of various TB-associated symptoms [9]; and clues to improved treatment approaches [12]. Considering this, metabo lomics has shed light on never before identified metabolic pathways in both man and the TBcausing bacteria, which in time will undoubtedly contribute to improved treatment strategies, and ultimately assist in curbing the epidemic.…”