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Dormant TB Cells Harden Outer Membrane, Thwarting Antibiotics, IIT Bombay–Monash Study Finds

The finding suggests that weakening the rigid lipid coat could restore the potency of existing TB drugs against persistent infections.

Overview

  • The peer-reviewed work, published in Chemical Science, was led by IIT Bombay with Monash University collaborators.
  • Using a biosafe Mycobacterium smegmatis model, researchers compared active and dormant states and mapped more than 270 membrane lipids.
  • Dormant cells accumulated long, waxy fatty layers and showed reduced cardiolipin, creating a tightly packed, rigid barrier to drug entry.
  • In growth-inhibition tests, dormant cells required two to ten times higher concentrations of rifabutin, moxifloxacin, amikacin, and clarithromycin, with rifabutin barely penetrating the rigid membrane.
  • The team reports non-genetic drug tolerance linked to reduced permeability and plans BSL-3 validation in M. tuberculosis alongside tests of membrane-permeabilising agents such as antimicrobial peptides.