‘I Am Trying to Unravel How Psychobiotics Communicate with the Brain and Alleviate Mental Disorders.’

With three post-doctorates in three countries, microbiologist Dr Basit Yousuf has been working on bacteria for almost a decade now. Currently working at the University of Ottawa (Canada), he told Kashmir Life that he has located and identified some Gamma-aminobutyric acid (GABA) and is now exploring how they pass the gut-brain axis and impact the brain.

KASHMIR LIFE (KL): What is microbiology and how it is relevant to human life?

DR BASIT YOUSUF (DBY):: Microbiology is a very vast field and is a study of microbes including various viruses, bacteria, and fungi, and how these microorganisms deal with the environment and what impact they leave on the environment and human life. I am particularly researching bacteria.

KL: Pandemics are usually caused by viruses. Does that mean bacteria have been vanquished over a period of time?

DBY: Not at all. I can say that you should take it as a faux. Bacteria as such are a powerhouse of infections and diseases which have terrible implications for people and consequently on the economy. Externally or internally, they leave a drastic impact as they cause serious infections in humans, animals and even plants. Some bacterial diseases include bacterial Pneumonia, stomach ulcer by Helicobacter pylori, food poisoning, and various skin infections by Staphylococcus aureus. Also, bacteraemia, which is an infection of the blood, is one of the top causes of death in Europe and North America. Surgical procedures are highly prone to bacterial infections as bacteria can enter the body through wounds, surgery sites, ventilators, and catheters. These infections can’t sometimes even be treated by antibiotics as bacteria have developed antibiotic resistance mechanisms. So, there is no such ratification that bacteria have vanquished.

KL: Cholera was considered a resident killer in Kashmir. As for now, it’s not as prominent as it was in the last 200 years. Does not it mean that we have defeated the occurrence of Cholera epidemics in Kashmir?

DBY: Epidemics could be caused by bacteria or viruses. New variants arise both in bacteria and viruses and any of these two could cause future pandemics. During the virus pandemics, bacterial and viral infections worked together to cause most of the deaths. It must be noted that there has been a great advancement in the development of vaccines against viruses but no vaccines against bacteria. One of the most important medical discoveries in human history was the discovery of antibiotics in the twentieth century against bacterial infections which transformed medicine. Beginning with Penicillin and later other antibiotics have been quite effective in the eradication and treatment of numerous bacterial infections. Unfortunately, most of the bacteria recently have developed antibody resistance mechanisms due to uncontrolled usage of antibiotics, which is truer with respect to Kashmir.  Antibiotics are losing their efficacy very fast and in the future, could be a trigger to a bacterial pandemic. One of my previous postdoc research projects was on the development of anti-microbial drugs other than antibiotics such as anti-microbial peptides, like bacteriocins.

KL: Tell us about how has been your journey from Kashmir to the world’s best laboratories.

DBY: I have done my schooling in Kuhroo, Handwara (Kupwara). I did my graduation from Amar Singh College, Srinagar. Due to high competition, I moved to Bangalore for my master’s in Biotechnology in 2005. After qualifying for the NET examination, I joined Central Salt and Marine Chemical Research Institute, Bhavnagar, Gujarat, for my PhD. My research was on soil metagenomics, which was based on unraveling bacteria community composition present in the soil. Metagenomics means identifying the bacterial composition based on DNA prints and then analysing their impacts on agriculture, the environment and improving soil productivity.

Dr Basit Yousuf Dar

KL: What was the main takeaway from your PhD?

DBY: Doing PhD is a great challenge as we must spend five years of our life working on a specific research area and performing a very deep analysis.  But with challenges, you have rewards. The biggest reward from PhD was getting in-depth knowledge, and a drastic change in vision of life, you see things differently and get to know the world, and you get a lot of patience as well as passion to use research as a tool to do the best. I published six research articles in peer-reviewed international journals with hundreds of citations.

Research-wise, I was one of the few researchers using metagenomics as a tool to study bacterial communities in India as it was a new technique. I found out about potential carbon dioxide fixing bacteria in the barren soil and how we could make use of these bacteria as a potential carbon dioxide sink, which could potentially alleviate the alarming issue of Global Warming. This is the hypothesis which I developed from my research and in coming years, maybe we could see some credential reports with deeper research that could provide a way to do this.

Also, we identified potential plant growth-promoting bacteria and the pathways involved at the genetic level which could help in improving agricultural productivity.

KL: You moved to the series of Post Doc, tell us about that?

DBY: After completing my PhD, I moved to South Africa, Cape Town, and did my postdoc at Stellenbosch University. My research was focused on extracting peptides from soil bacteria (Bacillus clausii and Bacillus amyloliquefaciens) and using them to treat bacteria-mediated skin infections. Antibiotic resistance has become one of the biggest threats to global health. We were trying to develop alternative therapeutic interventions to antibiotics. Thus, I was analyzing peptides to be effective in killing invasive methicillin-resistant Staphylococcus aureus bacterium under in vitro conditions and then analysing its efficacy in vivo.

Besides, I was also working on the antimicrobial activity of thin copper metal sheets against different bacterial pathogens. We showed copper sheets had antibacterial efficacy against six types of pathogenic bacteria. This research proved the applicability of copper plates in healthcare settings or utensils which could reduce the bacterial load to notable levels.

Additionally, I wrote a research proposal on Exploring bacterial talk in the gut Clostridia community toward disease prevention and health promotion, which was accepted by a funding agency from Japan, called the Japanese Society for the Promotion of Science (JSPS). It is one of the high-quality reputed funding agencies in Japan. They provided me with a two-year fellowship in collaboration with Kyushu University, Fukuoka, Japan.

In this research project, I worked on two bacterial pathogens, Clostridium difficile and Clostridium perfringens, which cause diarrhoea, stomach issues, and even could lead to death. We analysed how these bacteria talk with each other at molecular level called as quorum sensing and produce toxins which cause serious illnesses. We tried to manipulate the communication signals of these bacterial pathogens in order to control diseases caused by these bacteria. We performed the chemical synthesis of bacterial peptides, which are produced by one of the probiotic bacteria, Clostridium butyricum and used the peptides to attenuate communication and consequently toxin production and disease progression. This probiotic bacterium is currently being used to overcome diarrhoea-related issues.

KL: So, from Japan, you moved to Canada?

DBY: Yes, after that I moved to Canada for my third postdoctoral position at Canadian Blood Services. It is a national organization in Canada involved in distributing blood components like plasma, platelets and red blood cells to all major hospitals in Canada except hospitals in Quebec.

My research was on understanding the mechanism of bacterial contamination of platelet units. Due to Covid19, many people might have heard about the importance of platelets, as one of the therapeutic interventions. Platelet transfusions are an essential medicine to treat patients with bleeding disorders and cancers. Notably, these platelets remain stable only at room temperature and for bacteria, it is an ideal condition to proliferate. Platelets are manufactured from blood after blood donation camps.

During venepuncture, sometimes the potential opportunistic pathogenic bacteria like Staphylococcus aureus is introduced into the blood from the skin and consequently into platelet units. Despite strict screening of platelet units for bacterial contamination, some bacterial strains like that of S. aureus have the ability to escape screening. Once these contaminated units are transfused to patients, they can cause septic transfusion reactions as has been recently reported in US, UK, and Canada. These contaminated platelet units could be fatal to immune-compromised patients as they can suffer septic shock and thus can pose a serious risk to patients.

My research question was to unravel how S. aureus evades platelet immune defences, escapes detection in screening, and modulates platelet functionality. For this, I used CRISPR-CAS9-based mutation and RNA sequencing technology to study the mechanism which led us to unveil the genetic mechanism involved in platelet dysfunctionality and missed detection. This research will soon be published in an international journal.

KL: Has there been a technology that can manage the prevention of this inflection in platelets?

DBY: As far as instrumentation is concerned, we use BacT/ALERT 3D Microbial Identification System. This system is used to detect any bacteria present in the platelet units. But as I mentioned earlier, some bacteria have a mechanism to hide from the BacT/ALERT system. I believe underdeveloped and developing nations don’t have this system.

KL: What are you busy with, right now?

DBY: Currently, I am working as a research associate at the University of Ottawa, Canada, and here my research is on psycho-biotics and how they communicate with the brain and help in the alleviation of mental disorders like anxiety, depression, and more invasive Parkinson’s and Alzheimer’s diseases. Some gut bacteria (psychobiotics) produce neurotransmitters like Gamma-aminobutyric acid (GABA) which possibly reach the brain through the Gut-Brain axis. I have identified some new GABA-producing bacterial strains from the human gut. Now I am trying to explore the mechanism of how bacterial-produced/induced neurotransmitters reach the brain via the gut-brain axis using mice models and then I will assess its impact on mental health.

(Umaima Reshi processed the long interview.)

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