Award winning science The Holy Grail of Bacteria; Mysterious dark matter exposed

Ashwini Kumar, senior principal scientist, CSIR-Institute of Microbial Technology, Chandigarh, is one of the two winners of this year’s Shanti Swarup Bhatnagar Prize for Biological Sciences, the other being Madika Subba Reddy of the Center for DNA Printing and Diagnostics, Hyderabad. Kumar’s laboratory focuses on the mechanisms used by bacteria to develop drug resistance. In this interview, he explains how the bacteria that cause TB form clusters called biofilms, within which they hide from the immune system and antibiotics.

What is biofilm, the topic of your research?

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Ashwini Kumar, Senior Principal Scientist, CSIR-Institute of Microbial Technology, Chandigarh

Bacterial biofilms are communities of bacteria bound together by a matrix that the bacteria themselves make. The nature of the matrix is ​​the Holy Grail for scientists wishing to understand these communities and the behavior of the bacteria in them. Bacteria are social organisms and forming these communities is their natural way of life.

However, microbiological studies are largely based on growing bacterial cells as single-cell suspensions. Studying bacterial cells in such suspensions offers many advantages for understanding bacterial physiology, but, at the same time, we are studying them in an unnatural state.

The ability of pathogens to form biofilms acquires particular relevance in case of chronic infections. This is because these biofilms act as castles or bunkers in which bacterial cells can remain hidden from the immune system and antibiotics.

What is the role of biofilms in tuberculosis?

Textbooks describe the disease’s causative agent, Mycobacterium tuberculosis (Mtb), as an obligate intracellular pathogen. This term refers to pathogens that require a host cell to reproduce and survive. This belief about Mtb is based on observations that the bacterium is often seen inside macrophages (a certain type of cell) of an infected person.

Because of this perception, scientific studies have largely ignored the ability of Mtb cells to form biofilms. Being large structures composed of many bacterial cells and additional polymer materials, biofilms cannot typically form inside cells such as macrophages, which are much smaller. Thus, normally, extracellular bacteria form biofilms.

Although Mtb is defined as an obligate intracellular pathogen, large numbers of Mtb bacilli are also observed in extracellular spaces in the infected lung. This is where it becomes interesting to test the possibility that Mtb can form biofilms in these locations outside of host cells.

And, you have found that Mtb forms biofilms?

My laboratory has previously reported that reducing stress (something that inhibits bacterial growth) in the lung environment induces Mtb to form biofilms. We also demonstrated that Mtb cells use cellulose, a polymer often found in plant cell walls, to form these biofilms. Furthermore, inside these biofilms, Mtb becomes unresponsive to anti-TB agents.

What is the way to fight this?

We have demonstrated that cellulase, an enzyme, can disintegrate Mtb biofilm and re-sensitize the bacteria to drugs. We conducted experiments that show that in some cases of human tuberculosis, Mtb cells are enclosed in biofilms. We have conducted experiments on Mtb-infected mice and found that giving nebulized cellulase helped anti-TB drugs kill Mtb during infection.

Physicist Basudeb Dasgupta

dark matter is increasing

At TIFR, Mumbai, physicist Basudeb Dasgupta studies, among other things, the interface between particle physics and astrophysics. His theoretical work on subatomic particles called neutrinos, which span both the worlds of nuclear and astrophysics, and the mysterious “dark matter” earned him this year’s Shanti Swarup Bhatnagar Prize for Physics, awarded by Anindya of IISc Bangalore. Shared with Das. In this interview, Dasgupta explains what his studies have taught us.

How do you connect the physics of celestial bodies with particle physics?

Just as understanding atoms helps us understand the chemistry and properties of unusual materials, understanding particle physics helps us understand the behavior of astrophysical objects (and vice versa). To take one example, stars have extreme temperatures and pressures where many exotic subatomic particles are produced. In turn, these particles affect the star’s evolution by burning its nuclear fuel. Thus, understanding the new particles helps to better understand stellar evolution. Similarly, if we understand how a star burns its fuel, any deviation from this understood pattern, if observed, will increase the likelihood of discovering new particles and impacts that are possibly causing the departure.

What has your research on neutrinos taught us?

Neutrinos exist in different types, known as flavors, and are known to change from one flavor to another. Inside massive stars, this process is predicted to accelerate under certain conditions, known as an “instability”. This instability is caused by the coherent interaction of many neutrinos with each other in a dense atmosphere. We have proven mathematically that a specific condition must be met for instability to occur. We have predicted that this may actually occur deep inside stars. It is believed to influence the explosion of the star and the formation of chemical elements essential for life in the universe.

What is dark matter, which has been theorized but not yet fully explained?

Observations of galaxies, clusters of galaxies, and the universe at its largest contradict theoretical predictions. These objects have rotating and oscillating motions that can only be explained if they have more mass than is apparent. This extra mass should result in a new type of matter that interacts very little, if at all, with light or normal atoms. Discovering the elementary components of this so-called “dark matter” is a leading goal of modern science.

What has your research been like in this area?

We analyze the possibilities of the microscopic nature of dark matter using theoretical physics, mathematics and computers. The work involves writing a probabilistic “model”, calculating its results, and comparing these predictions to observations made by specialized telescopes from international teams.

Among the possible dark matter candidates are very low-mass black holes. Although these have not yet been ruled out, our work has placed strong constraints on the fraction of dark matter that can be attributed to very low-mass black holes.

In other work, we have predicted novel signatures of dark matter accreting into stars. Although these studies do not yet tell us what dark matter is, they do tell us what it is not, and may lead future efforts in more useful directions.

Shanti Swarup Bhatnagar Prize for Science and Technology was awarded to 12 researchers in seven disciplines. The annual awards, given by the Council of Scientific and Industrial Research, recognize scientists under the age of 45 for notable or outstanding research. Read interviews with all 12 award winners in the award-winning science series

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