Tuberculosis has a gene link

In this edition of Science Notebook, we also see how an international team of scientists has detected the most powerful cosmic ray in more than three decades.

Published : Feb 09, 2024 13:33 IST - 8 MINS READ

IscS and SUF-mediated iron-sulphur cluster biogenesis controls persistence of Mtb.

IscS and SUF-mediated iron-sulphur cluster biogenesis controls persistence of Mtb. | Photo Credit: Mayashree Das, IISc (created using Biorender)

Researchers at the Indian Institute of Science (IISc), Bengaluru, in collaboration with the National Centre for Biological Sciences and the Institute for Stem Cell Science and Regenerative Medicine (both also in Bengaluru), have discovered an important mechanism that allows the tuberculosis (TB) bacterium, Mycobacterium tuberculosis (Mtb), to persist in the human host for decades. A single gene involved in the production of iron-sulphur clusters could be crucial for this persistence. The study was recently published in Science Advances.

“Mtb needs humans to survive. In many cases of Mtb infection, the immune system can detect the bug and clear it out,” explained Mayashree Das, first author of the study. However, in several asymptomatic individuals, Mtb hides within deep oxygen-limiting pockets of the lung and enters a state of dormancy in which it does not divide and is metabolically inactive, thus successfully hiding from the immune system and TB drugs. Because of this persistence, there is a bacterial reservoir in a subset of the human population that can at any point reactivate and cause infection. “Unless we understand persistence,” said Amit Singh, the corresponding author of the study, “we will not be able to eradicate TB.”

In IISc’s state-of-the-art Bio Safely Level-3 facility, Singh’s team grew Mtb in liquid cultures containing special supplements needed for its growth. Several proteins in Mtb depend on iron-sulphur clusters—consisting of iron and sulphur atoms organised in various configurations—to function.

According to the IISc release, the iron-sulphur cluster-containing proteins are important for essential processes such as energy production by respiration, enabling the bacteria to survive the harsh conditions of the lungs and cause infection. These clusters are mainly produced by a set of genes in Mtb called “SUF operon”, which get switched on together. However, there is another single gene called IscS that can also produce the clusters. So why would the bacterium need both?

To understand this, the researchers generated a mutant version of Mtb that lacked the IscS gene. They found that under normal and oxygen-limiting conditions, iron-sulphur clusters are produced mainly by the action of the IscS gene. But when the bacterium faces a lot of oxidative stress, iron atoms get released damaging the clusters, leading to increased demand for more clusters and switching on of SUF operon.

Using mice models, the researchers also found how IscS contributed to disease progression. They found that IscS kept the activation of the SUF operon in check, causing the persistent, chronic infection typically seen in TB patients. The absence of IscS, however, led to severe disease in the infected mice and the depletion of both IscS and SUF operon, which dramatically reduced the persistence of Mtb in mice. The researchers also found that bacteria lacking the IscS gene were more likely to be killed by certain antibiotics. The team suggested that combining antibiotics with drugs targeting IscS and SUF might prove to be more effective than antibiotics alone.

Dark Energy Survey confirms accelerated expansion of universe

The history of the expansion of the universe can be traced by comparing recessional velocities (redshifts) with distances measured for each supernova. The Dark Energy Survey results show that the expansion has been accelerating with cosmic time.

The history of the expansion of the universe can be traced by comparing recessional velocities (redshifts) with distances measured for each supernova. The Dark Energy Survey results show that the expansion has been accelerating with cosmic time. | Photo Credit: DES Collaboration

In 1998, astrophysicists discovered that the universe is expanding at an accelerating rate. This was attributed to a mysterious entity called dark energy that makes up about 70 per cent of the universe. The discovery was surprising because, on the basis of earlier observations, astrophysicists believed that the expansion should be slowing down due to gravity.

This revolutionary discovery was the result of observations on Type “one-A” supernovae, which occur when extremely dense dead stars, known as white dwarfs, reach a critical mass and explode. This work won the Physics Nobel in 2011.

Now, 25 years later, scientists working on the Dark Energy Survey (DES) have released the results of an unprecedented analysis—performed with four different techniques, including the technique used in 1998—to further understand the nature of dark energy and measure the expansion rate of the universe. They placed the strongest constraints on the expansion of the universe ever obtained with the DES supernova survey.

DES is an international collaboration involving more than 400 scientists from over 25 institutions led by the Fermi National Accelerator Laboratory, US. DES mapped an area almost one-eighth the entire sky using the Dark Energy Camera, a 570-megapixel digital camera built by Fermilab mounted on the Víctor M. Blanco Telescope at the National Science Foundation’s Cerro Tololo Inter-American Observatory, Chile. DES scientists took data for 758 nights across six years. The survey stopped taking data in January 2019.

In a presentation at the 243rd meeting of the American Astronomical Society on January 8, using the full five-year data set that included about 1,500 new Type-Ia supernovae, DES astrophysicists reported that the survey results were consistent with the now-standard cosmological model of a universe with an accelerated expansion. Yet, the findings are not definitive enough to rule out a possibly more complex model, according to the release from Fermilab.

Since the critical mass is nearly the same for all white dwarfs, all Type-Ia supernovae have approximately the same actual brightness. So, when astrophysicists compare the apparent brightness of two Type-Ia supernovae as seen from the earth, they can determine their relative distances from the earth.

The history of cosmic expansion is traced using large samples of supernovae spanning a wide range of distances. For each supernova, they combine its distance with a measurement of its “redshift”, a measure of how quickly it is receding from the earth due to the expansion of the universe. They use that history to determine whether the dark energy density has remained constant or changed over time.

“As the universe expands, the matter density goes down,” said Rich Kron, DES director and its spokesperson. “But if the dark energy density is a constant, that means the total proportion of dark energy must be increasing as the volume increases.”

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The standard cosmological model—the “‘Lambda cold dark matter’ (ΛCDM) model—is based on the dark energy density being constant over cosmic time. It tells us how the universe evolves, using just a few features, such as the density of matter, type of matter, and behaviour of dark energy. The supernova method constrains two of these features very well: matter density and a quantity “w” that indicates whether the dark energy density is constant or not.

According to the ΛCDM model, the density of dark energy in the universe is constant, which means it does not get diluted as the universe expands. If this is true, the parameter w should equal –1. “w is tantalisingly not exactly on –1, but close enough that it’s consistent with –1,” said Tamara Davis, co-convener of DES’ supernova working group. “A more complex model might be needed. Dark energy may indeed vary with time.”

A new cosmic particle of unknown origin

An illustration of Telescope Array. Three fluorescence telescopes observe the ultraviolet light given off by an air shower, while an array of surface detectors register the particles as they strike the ground.

An illustration of Telescope Array. Three fluorescence telescopes observe the ultraviolet light given off by an air shower, while an array of surface detectors register the particles as they strike the ground. | Photo Credit: Wikimedia Commons

An international team of scientists that includes the Telescope Array Collaboration and others, led by the Japanese scientist Toshihiro Fujii from Osaka Metropolitan University, has detected the most powerful cosmic ray seen in more than three decades. But its origin remains a mystery. Hypotheses to explain this event, which has eluded explanation with known physics, include stronger foreground intergalactic magnetic fields and unknown particle physics at high energies. The finding was reported in the November 24 issue of Science.

The measured energy of this puzzling cosmic ray particle is about 240 exa-(1018) electronvolts (EeV), more than a million times higher than that achieved by artificial particle accelerators. This makes it the second highest energy cosmic ray particle ever observed. The first, called the Oh-My-God (OMG) particle, was detected in 1991 and had a measured energy of around 320 EeV.

Cosmic rays are charged particles, like protons, that arrive on the earth from space. At low energies, they mostly originate from the sun, but at high energies they are believed to be emitted by nearby active galaxies. Such ultra-high-energy particles are expected to be deflected only a little by the foreground magnetic fields, thereby making it relatively simpler to trace back their origins. But in this case such tracing back has revealed no obvious source galaxy.

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Fujii and his team have been conducting the Telescope Array experiment since 2008, chasing such high-energy cosmic ray particles. This instrument consists of 507 scintillator surface stations covering an expansive detection area of 700 sq km at about 1,400 m above sea level in Millard County, Utah, US. The experiment detects air showers induced by ultra-high-energy cosmic rays using a combination of ground array and air-fluorescence techniques.

On May 27, 2021, while doing a routine data check on the Telescope Array, Fujii detected a particle with a whopping energy of 244 EeV. “When I first discovered this ultra-high-energy cosmic ray, I thought there must have been a mistake, as it showed an energy level unprecedented in the last three decades,” said Fujii. “No promising astronomical object matching the direction from which the cosmic ray arrived has been identified, suggesting possibilities of unknown astronomical phenomena and novel physical origins beyond the standard model,” Fujii remarked.

The particle has been nick-named “Amaterasu” after the sun goddess that, according to Shinto beliefs, was instrumental in the creation of Japan.

Fujii and his team are in the process of upgrading the Telescope Array to be four times as sensitive as before so that they can conduct a more detailed investigation into the source of such particles.

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