Sensory control of nematode-microbe and microbe-microbe interactions
Olfactory cues as regulators of lipid metabolism, stress response and innate immunity in C. elegans
C. elegans as a model host for microbial pathogens.
Non-traditional signals for activation of immune response
This involves study of perception of three classes of microbial pathogens, Gram-negative bacteria, Gram-positive bacteria and fungi, by model host C. elegans. These microbes present different features across:
(i) Cell size (1-10 micron)
(ii) Cell wall components (lipopolysaccharide, peptidoglycan, lipoteicjhoic acid, sugars)
(iii) Pathogen associated molecular patterns (lipopolysaccharide, lipotichoic acid, capsule etc)
(iv) Secondary metabolites (ketones, aldehydes, alcohols, aromatic hydrocarbons, pyocyanin)
(v) Tissue tropism in mammalian host (lungs, brain, epithelial surfaces) and in C. elegans (skin, intestine, rectal epithelium)
How does C. elegans recognize the pathogens in the absence of classical pattern recognition receptors such as the toll family molecules*?
C. elegans is allowed to chose between microbes in a chemo taxis based preference assay. We use a number of mutants and transgenic C. elegans strains generated in the lab to understand if certain neurons in the Amphid sensory organ of C. elegans help the worm differentiate between these microbe.
* C. elegans genome encodes a single toll family molecule called tol-1.
Immuno metabolism
C. elegans has to protect itself during encounters with pathogenic microbes in its microhabitat of decomposing vegetation containing both pathogenic microbes as well as non-pathogenic ones. Lacking specialized immune cells, C. elegans relies entirely on its innate immune system to combat infections, by producing an array of immune effectors including lectins, proteases, and antimicrobial peptides. Thus, mounting an immune response is energetically expensive; however, the celluar source of energy fuels it remains mostly unknown. The primary energy reserve in C. elegans is triacyl glycerol (TAGs) stored in lipid droplets. We hypothesized that droplets are utilized to fuel immune response during infections. In a study on lipid droplet utilization during infection, with Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Enterococcus faecalis and Cryptococcus neoformans, we found that all pathogens induced the utilization of lipid droplets, but with different kinetics. We find that E. faecalis induces transcriptional upregulation of genes involved in lipid breakdown, while inducing downregulation of lipid synthesis genes. The transcriptional modulation is partly orchestrated by a nuclear hormone receptor NHR-49, ortholog of human PPARalpha, expressed in the nervous system. Thus, NHR-49 regulates an immuno-metabolic axis of survival during infection with E. faecalis [Dasgupta et al. 2020], a process termed immuno metabolism.
Neuronal Control of Lipid metabolism by STR-2 G protein coupled receptor promotes longevity in C. elegans.
C. elegans genome encodes as many as 1500 GPCRs. Some of these GPCRs allow worms to sense olfactory signals from bacteria such as diacetyl which serve as food for nematodes. We hypothesize that GPCRs responsible for finding food affect reproduction, flight and fight response and longevity. We have recently shown that an olfactory GPCR, STR-2, expressed in three sensory neurons of this nematode regulates lipid metabolism and life span at high temperature of rearing (20 to 25C) but not at low temperature. We find that STR-2 signaling is necessary for temperature response of AWC and ASI neurons. STR-2 signaling in these neurons controls expression of fatty acid desaturases and diacyl glycerol acyl transferases in the intestine of the nematodes (Dixit et al, AGING CELL 2020).
Behavioral adaptation of C. elegans to pathogenic bacteria
C. elegans can show avoidance response to P. aeruginosa [Zhang and Bargmann, Nature 2005] and Serratia marcescens. The former is a learned behavior. This behavioral adaptation increases survival of C. elegans on a lawn of pathogenic P. aeruginosa. One of the ligand receptor pair identified in this case is pyochelin (secondary metabolite) of P. aeruginosa recognized by ASJ amphid neuron of C. elegans [Kim lab, Cell 2014]. P. aeruginosa has a large and complex repertoire of secondary metabolites, and we have evidence that C. elegans aversion response is driven by additional ligands. We have performed a screen of transposon insertion mutants of P. aeruginosa to identify additional ligands which stimulate C. elegans neurons and induce behavioral adaptation/aversion in C. elegans. This has led to identification of 18 P. aeruginosa genes that affect C. elegans aversion response. We study the molecular nature of receptor ligand interactions using P. aeruginosa mutants and C. elegans.
Swarming in Pseudomonas aeruginosa
Swarming in Pseudomonas aeruginosa is a coordinated movement of a population of bacteria over semi-solid surfaces (0.5% to 0.7% agar). Quorum is an important component of swarming and so is flagellar motility. However, the motivations for swarming motility in bacteria are largely unexplored. The lab is interested in finding environmental signals which regulate swarming. The signal could be nutrition, presence of a competitor or antibiotic/immune pressure.
swarming.aviQuestions of interest
1. Why do bacteria swarm?
2. Do two component system of P. aeruginosa allow signal integration and swarming?
3. Is swarming context dependent?
4. is swarming different from bioflim formation?
5. How does quorum sensing regulate a locomotion behavior (swarming) and a "stay-put'' behavior (biofilm)?
