Identification of gut pathogen receptors as sentinels of small molecules

Work done in the lab of Prof. Vanessa Sperandio at University of Texas Southwestern Medical Center (presently at University of Wisconsin Madison).

About author

Aman is a postdoctoral associate at Yale School of Medicine in the laboratory of Prof. Andrew Goodman. Prior to this, Aman received his doctoral degree from the University of Texas Southwestern Medical Center in the laboratory of Prof. Vanessa Sperandio. Aman did his undergraduate studies in Biotechnology at the Indian Institute of Technology Madras. Aman values the importance of mentorship in professional success and is keen to pass on the knowledge to the next generation of scientists. Aman is co-leading the mentorship program at Yale as a part of the Yale Postdoctoral Association, where he aims to create an inclusive environment for postdocs from diverse backgrounds and provide resources to promote good mentorship practices. On a personal front, Aman is an avid hiker and is currently exploring different state parks in the New England region of the United States. In his free time, Aman indulges himself in finding the best ice cream places and playing board games with friends.

Interview

How would you explain your research outcomes to the non-scientific community?

The human gastrointestinal (GI) tract is a unique ecosystem, home to the vast microbial communities collectively known as the gut microbiota. Resisting colonization by intruders in the GI tract is a fundamental function of a healthy microbiome. The human gut acts as a reservoir for numerous small molecules due to dietary intake and host or microbial metabolic processes (1). Understanding the role of these small molecules in health and disease is central to advancing our knowledge of what constitutes a healthy gut environment. Indole and indole-like molecules, including the neurotransmitter serotonin, obtained upon the metabolism of dietary tryptophan, are abundantly present in the human gut. Prior to my doctoral research at the University of Texas Southwestern Medical Center in Dr. Vanessa Sperandio’s lab, the role of these small molecules in host-microbiome-pathogen interactions was unknown. My Ph.D. research established the importance of indole and serotonin in pathogen resistance. My research identified the bacterial receptor that detects these signals in the gut and enables pathogens to change their behavior (2-4) (Figure 1).

Fig. 1. Gut small molecules protect the host against gut pathogens. Tryptophan metabolites such as microbiome-produced indole or host-produced serotonin repress gut pathogen colonization. Gut pathogens such as Enterohemorrhagic E. coli or Citrobacter rodentium utilize membrane-bound histidine kinase CpxA or cytoplasmic indole sensing regulator (IsrR) as sensors to gauge the metabolic landscape of the gut and colonize under favorable conditions.

How do these findings contribute to your research area?

My work identified a bacterial receptor that is conserved across other enteropathogens and it can be employed as a drug target against a variety of enteric pathogens. This receptor’s recognition of bacterial and host-derived signals biochemically integrates host-bacterial interactions. Understanding these mechanisms is essential for devising modern medical strategies that may enable modulating the microbiome against pathogen infection.

“Work identified a bacterial receptor that is conserved across other enteropathogens and it can be employed as a drug target against a variety of enteric pathogens”

What was the exciting moment during your research?

The two questions that always excite me are the whats and hows. The first exciting moment was when we identified a phenotype – that was a what’s happening moment. However, the best moment was when I got to the how part. I believe identifying the mechanism and how indole and serotonin were sensed by gut pathogens was the most exciting moment for me during my Ph.D. research.

What do you hope to do next?

I am continuing to investigate the gut microbiome and how it is affected by various environmental perturbations such as medical drugs or diet. Currently, I am pursuing a postdoc in the laboratory of Dr. Andrew Goodman at Yale University, where I am combining epidemiological approaches with gnotobiotics to mechanistically understand the effect of these xenobiotics on the human microbiome in the context of health and disease. I believe that our gut is one of the most therapeutically tractable organs, which has an enormous effect on the human body, and understanding these processes can help us devise strategies to improve human health and build approaches toward personalized medicine.

Where do you seek scientific inspiration from?

My scientific inspiration has always been my mentors – ranging from peer mentors to academic advisors. My peers during my undergraduate days helped me figure out my passion for research, and thereafter I have been extremely fortunate to work with some outstanding people in the field who inspire me to do amazing science. I have also been extremely fortunate to work under the supervision of outstanding scientists like my Ph.D. and postdoc advisors, from whom I continue to seek inspiration.

Reference

Copy Editor

Sukanya Madhwal

Ph.D. student at inStem Bangalore

Sukanya hails from a small town, kotdwara in Uttarakhand. She completed her Masters’ degree in Biotechnology from Banasthali Vidyapith, Rajasthan. After this, she served as a graduate teacher for one year at P.G. College, Kotdwara, Uttarakhand. In 2014, she qualified for the JGEEBILS exam conducted by NCBS/TIFR and joined as a Research Scholar (Ph.D. student) in Dr. Tina Mukherjee’s lab at inStem. Currently, she continued working as a bridging post-doc in Dr. Tina Mukherjee’s lab. Besides work, she loves reading non-fiction books, enjoys gardening, and cooking delicious food.

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