The nematode Caenorhabditis elegans displays a chemotaxis behavior to tuberculosis-specific odorants

Abstract

A simple, affordable diagnostic test for pulmonary tuberculosis (TB) is urgently needed to improve detection of active Mycobacterium tuberculosis. Recently, it has been suggested that animal behavior can be used as a biosensor to signal the presence of human disease. For example, the giant African pouched rats can detect tuberculosis by sniffing sputum specimens while trained honeybees respond to three of the volatile organic compounds (VOCs) detected in the breath of TB positive patients by proboscis extension. However, both rats and honeybees require animal housing facilities and professional trainers, which are outside the scope of most disease testing facilities. Here, we report that the innate olfactory behavioral response of the roundworm nematode Caenorhabditis elegans can be used to detect the TB-specific VOCs methyl p-anisate, methyl nicotinate, methyl phenylacetate and o-phenylanisole, in chemotaxis assays. Dauer larvae, a long-lived stress resistant alternative development state of C. elegans in which the animals can survive for extended periods of time in dry conditions with no food, were also demonstrated to detect the VOCs. We propose that exposing naive dauer larvae to TB-related VOCs and recording their response in this behavioral assay could lead to the development of a new method for TB diagnostics using breath as the sample type.

A Caenorhabditis elegans behavioral assay distinguishes early stage prostate cancer patient urine from controls

“…The potential for animals to sense malignancy has received increasing attention since the phenomenon was first described over three decades ago ( Williams and Pembroke, 1989 ). Since the first report of C. elegans accurately classifying cancer samples by Hirotsu et al (2015) , similar methods have been applied using C. elegans to detect sepsis ( Tee et al, 2019 ) and tuberculosis-specific odorants ( Neto et al, 2016 ). Two of the VOCs proposed to be increased in PrCa urine samples by Khalid et al (2015) were found to elicit behavioral attraction of C. elegans under our assay conditions.…”

C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples

“…After 60 minutes, animals were counted and a chemotaxis index (CI) was calculated as follows: (number of animals in the odorant area) – (number of animals in the control area) / total number of animals tested. Chemotaxis assays were performed in triplicate on separate chemotaxis plates, to ensure assay reproducibility 53 .…”

A machine learning based analysis to probe the relationship between odorant structure and olfactory behaviour inC. elegans

“…The first step in analyzing the structure-behavior relationship is data curation. To this end, we carried out a literature survey to make a list of chemicals with known corresponding C. elegans behaviours [5, 6, 9, 10, 12, 14, 31–55]. However, different concentrations of some of the chemicals have been reported to show conflicting C. elegans behaviours.…”

“…These studies also gave way to an interest in getting insights into the dynamics of worm movements during chemotaxis [11, 12], with a large number of works now focusing on finding the accurate mathematical model that can describe the same [13]. Since then, there is a growing list of known C. elegans attractants and repellents, which has lead to efforts in harnessing the olfactory behaviour to aid diagnostics in tuberculosis [14] and cancer [15]. The individual or group of neurons involved in the sensing have been identified using ablation [9, 16] and RNAi studies [17].…”