12^th January 2023

– Narmada Khare

In two recent studies, researchers at the Indian Institute of Science (IISc) and Unilever have collaborated to develop computational models of bacterial cell walls that can speed up the screening of antimicrobials – molecules which can kill disease-causing bacteria.

Schematic illustration of surfactant molecules interacting with the bacterial peptidoglycan cell wall. The greater the tendency for surfactants to form aggregates, the lower is bacterial kill efficacy. Credit: Pradyumn Sharma-

Each bacterial cell is enveloped by a cell membrane, which is in turn surrounded by a cell wall. Some bacteria like Escherichia coli (E. coli) are Gram-negative – their cell walls contain a layer of peptide-sugar complexes called peptidoglycans and an outer lipid membrane. Others such as Staphylococcus aureus (S. aureus) are Gram-positive – their cell walls only have several layers of peptidoglycans.

Antimicrobials kill bacteria either by disrupting the cell wall’s lipid membrane and destabilising the peptidoglycan layer, or by translocating through the cell wall layers and disrupting the cell membrane inside. However, the actual mechanisms of interaction between antimicrobial molecules and these cellular barriers are poorly understood. “The cell envelope is a big part of this puzzle, and it is often overlooked,” says Pradyumn Sharma, a former PhD student at the Department of Chemical Engineering (CE), IISc, and one of the authors.

In one study, the team created an ‘atomistic model’, a computer simulation that recreates the structure of the cell wall down to the level of individual atoms. They incorporated parameters such as the sizes of sugar chains in the peptidoglycans, the orientation of peptides, and the distribution of void size.

“The structure of the peptidoglycan layer is semi-permeable, because nutrients and proteins that bacteria need, have to pass through,” explains Ganapathy Ayappa, Professor at CE and corresponding author. These are the same voids that the antimicrobials also pass through. Rakesh Vaiwala, a Research Associate at CE and one of the authors, adds that their team is the first to propose a comprehensive molecular model of the cell wall for S. aureus.

Using the supercomputing facility at IISc, the team tested the effectiveness of their model with several known antimicrobials. One of these, melittin, a short peptide, binds with higher efficiency to the E. coli cell wall than that of S. aureus. The researchers found that melittin interacts with peptides involved in a process called transpeptidation in peptidoglycan biosynthesis, and can potentially disrupt cell wall integrity. Thymol, a naturally occurring small molecule, translocated rapidly through the whole stack of peptidoglycans in the cell wall of S. aureus.

In the other study, the team used their model to compare the movement of different surfactant molecules through the peptidoglycan layer in E. coli. Like detergents, surfactants have a water-loving ‘head’ attached to a water-avoiding ‘tail’ chain. The team showed for the first time the link between the length of the tail and antimicrobial efficacy of surfactants. Surfactants like laurate with shorter chains translocated more efficiently than longer chain oleate. This was corroborated by experiments carried out by scientists in the Unilever team, which showed that shorter chain surfactants killed bacteria at a higher rate than surfactants with longer chains.

The team also collaborated with Jaydeep Kumar Basu, Professor in the Department of Physics, to create vesicles composed of E. coli extract and observed their interaction with surfactants under a microscope. The vesicles were found to burst open at a much faster in the presence of laurate compared to oleate.

“The goal with Unilever is to facilitate rapid screening of molecules using the computational models we have developed, to narrow down the search for potential antimicrobials to a smaller subset of molecules which can be tested in the laboratory,” explains Ganapathy Ayappa.

REFERENCES:

Sharma P, Vaiwala R, Parthasarathi S, Patil N, Verma A, Waskar M, Raut JS, Basu JK, Ayappa KG, Interactions of surfactants with the bacterial cell wall and inner membrane: Revealing the link between aggregation and antimicrobial activity, Langmuir (2022).

https://doi.org/10.1021/acs.langmuir.2c02520

Vaiwala R, Sharma P, Ayappa KG, Differentiating interactions of antimicrobials with Gram-negative and Gram-positive bacterial cell walls using molecular dynamics simulations, Biointerphases (2022).

https://doi.org/10.1116/6.0002087

CONTACT:

K Ganapathy Ayappa

Professor, Department of Chemical Engineering

Indian Institute of Science (IISc)

Email: ayappa@iisc.ac.in

Phone: +91-80-2293 2769

Lab website: https://kgalabiisc.wixsite.com/kgalab

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.

b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.

16^th January 2023

Astronomers from McGill University in Canada and the Indian Institute of Science (IISc) in Bengaluru have used data from the Giant Metrewave Radio Telescope (GMRT) in Pune to detect a radio signal originating from atomic hydrogen in an extremely distant galaxy. The astronomical distance over which such a signal has been picked up is the largest so far by a large margin. This is also the first confirmed detection of strong lensing of 21 cm emission from a galaxy. The findings have been published in the Monthly Notices of the Royal Astronomical Society.

Atomic hydrogen is the basic fuel required for star formation in a galaxy. When hot ionised gas from the surrounding medium of a galaxy falls onto the galaxy, the gas cools and forms atomic hydrogen, which then becomes molecular hydrogen, and eventually leads to the formation of stars. Therefore, understanding the evolution of galaxies over cosmic time requires tracing the evolution of neutral gas at different cosmological epochs.

Illustration showing detection of the lensed 21 cm atomic hydrogen emission signal from a distant galaxy. Credit: Swadha Pardesi

Atomic hydrogen emits radio waves of 21 cm wavelength, which can be detected using low frequency radio telescopes like the GMRT. Thus, 21 cm emission is a direct tracer of the atomic gas content in both nearby and distant galaxies. However, this radio signal is extremely weak and it is nearly impossible to detect the emission from a distant galaxy using current telescopes due to their limited sensitivity. Until now, the most distant galaxy detected using 21 cm emission was at redshift z=0.376, which corresponds to a look-back time – the time elapsed between detecting the signal and its original emission – of 4.1 billion years (Redshift represents the change in wavelength of the signal depending on the object’s location and movement; a greater value of z indicates a farther object).

Images of the atomic hydrogen signal, the detection spectrum and the lens. Credits: Left and middle panels: Chakraborty & Roy, GMRT/NCRA-TIFR Right panel: ESA/NASA HST and eHST/STScI/CADC

Using GMRT data, Arnab Chakraborty, postdoctoral researcher at the Department of Physics and Trottier Space Institute of McGill University, and Nirupam Roy, Associate Professor, Department of Physics, IISc have detected a radio signal from atomic hydrogen in a distant galaxy at redshift z=1.29.

“Due to the immense distance to the galaxy, the 21 cm emission line had redshifted to 48 cm by the time the signal travelled from the source to the telescope,” says Chakraborty. The signal detected by the team was emitted from this galaxy when the universe was only 4.9 billion years old; in other words, the look-back time for this source is 8.8 billion years.

This detection was made possible by a phenomenon called gravitational lensing, in which the light emitted by the source is bent due to the presence of another massive body, such as an early type elliptical galaxy, between the target galaxy and the observer, effectively resulting in the “magnification” of the signal. “In this specific case, the magnification of the signal was about a factor of 30, allowing us to see through the high redshift universe,” explains Roy.

The team also observed that the atomic hydrogen mass of this particular galaxy is almost twice as high as its stellar mass. These results demonstrate the feasibility of observing atomic gas from galaxies at cosmological distances in similar lensed systems with a modest amount of observing time. It also opens up exciting new possibilities for probing the cosmic evolution of neutral gas with existing and upcoming low-frequency radio telescopes in the near future.

Yashwant Gupta, Center Director at NCRA, said, “Detecting neutral hydrogen in emission from the distant Universe is extremely challenging and has been one of the key science goals of GMRT. We are happy with this new path breaking result with the GMRT, and hope that the same can be confirmed and improved upon in the future.”

The Giant Metrewave Radio Telescope was built and is operated by NCRA-TIFR. The research was funded by McGill and IISc.

REFERENCE:

Chakraborty A, Roy N, Detection of H I 21 cm emission from a strongly lensed galaxy at z ∼ 1.3, Monthly Notices of the Royal Astronomical Society (2023), Volume 519, Issue 3. https://doi.org/10.1093/mnras/stac3696

CONTACT:

Arnab Chakraborty
Postdoctoral researcher
Department of Physics and Trottier Space Institute
McGill University
Email: arnab.chakraborty2@mail.mcgill.ca
Phone: (+1) 5148295756

Nirupam Roy
Associate Professor
Department of Physics
Indian Institute of Science (IISc)
Email: nroy@iisc.ac.in
Phone: 7337687132

IISc Office of Communications
Email: news@iisc.ac.in

NCRA-TIFR:
Yashwant Gupta
Email: ygupta@ncra.tifr.res.in
Phone: 020-25719242

CH Ishwara-Chandra
Email: ishwar@ncra.tifr.res.in
Phone: 9403136630

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.