Scanning electron micrograph of the Mycobacterium tuberculosis bacteria. Credit: NIAID
Microbiologists have deciphered how Mycobacterium tuberculosis (Mtb), a bacterium that causes TB, can lurk in human hosts for a long time1.
They have shown that the pathogen uses a single protein – cysteine desulfurase (IscS) – along with another set of proteins to thrive in the oxygen-poor environments of human immune cells without causing severe infection.
These parasitic proteins may act as potential drug targets, says a team of researchers at the Indian Institute of Science in Bengaluru.
The bacterium persists in host cells by using more than 50 proteins, including two protein systems (IscS and Suf). All these proteins have clusters of iron-sulfur (Fe-S) atoms.
To better understand this, the scientists, led by Amit Singh, separately infected mice with two Mtb strains – a wild type and a mutant that lacks IscS. Singh and colleagues Mayashree Das and Nagasuma Chandra then tracked host-parasite interactions using multiple techniques, including a fluorescent biosensor and fluorophores.
The team, supported by Aswin Sai Narain Seshasayee at the National Centre for Biological Sciences and Sunil Laxman at the Institute for Stem Cell Science and Regenerative Medicine in Bengaluru, found that the absence of IscS derailed the parasite’s replication by disrupting its metabolism, redox balance and respiratory potential. IscS protects it against oxidative stress, oxygen-poor conditions and anti-TB drugs, allowing Mtb to attain an intermediate degree of virulence.
Drugs designed to inhibit IscS and Suf could benefit TB patients with HIV infection and reverse antimicrobial resistance, says Singh.
