Indian scientists decode how TB bacterium persists in human body

Researchers at the Indian Institute of Science IISc have decoded the mechanism that helps the tuberculosis TB bacterium to persist in the human body for decadesIn the study published in the journal Science Advances they described a single gene that aids in the production of ironsulphur clusters key for the persistence of the TB bacteriumThese ironsulphur clusters help the bacteria in energy production by respiration and also help it to survive harsh conditions of the lungs and cause infectionTB is caused by the bacterium Mycobacterium tuberculosis Mtb which can be present in the human body for decades without any symptomsWhile in many cases the immune system can detect Mtb and flush it out sometimes the bug tends to hide within deep oxygenlimiting pockets of the lung and lie in a dormant state said Mayashree Das first author and doctoral student at the Department of Microbiology and Cell Biology MCB IIScDue to persistence there is a bacterial reservoir in a subset of the human population at any point which can reactivate and cause infection Unless we understand persistence we will not be able to eradicate TB said Amit Singh Associate Professor at MCB and corresponding author of the study in a statementTo understand how Mtb builds ironsulphur clusters the team grew Mtb in liquid cultures in the lab Ironsulphur clusters are mainly produced by the SUF operon in Mtb a set of genes that get switched on together However they found another single gene called IscS that can also produce the clustersTo explore whether the bacterium needs both the team generated a mutant version of Mtb without the IscS gene They found that during normal and oxygenlimiting conditions the IscS gene produces ironsulphur clustersHowever oxidative stress damages the clusters which increases demand for producing more clusters This switches on the SUF operonFurther the team also explored how the IscS gene contributes to disease progressionMice models were infected with the mutant version of Mtb lacking the IscS gene The lack of the IscS gene led to severe disease in the infected mice rather than a persistent chronic infection typically seen in TB patientsThis is because in the absence of the IscS gene the SUF operon is highly activated albeit in an unregulated fashion leading to hypervirulence Depleting both IscS and the SUF system dramatically reduced the persistence of Mtb in mice the team said in the studyThey found that the IscS gene keeps the activation of the SUF operon in check causing persistence in TBThe researchers also noted that bacteria lacking the IscS gene were more likely to be killed by certain antibioticsIt becomes sensitive to some antibiotics and resistant to some We would also like to explore this further Das saidThe team suggests that combining antibiotics with drugs targeting IscS and SUF might be more effectiveThis story has been sourced from a third party syndicated feed agencies Midday accepts no responsibility or liability for its dependability trustworthiness reliability and data of the text Midday managementmiddaycom reserves the sole right to alter delete or remove without notice the content in its absolute discretion for any reason whatsoever