Peptidyl-prolyl isomerase-B is involved in biofilm formation and a generic target for drug repurposing-based intervention.

Tuberculosis (TB), a disease caused by (), takes one human life every 15 s globally. Disease relapse occurs due to incomplete clearance of the pathogen and reactivation of the antibiotic tolerant bacilli. , like other bacterial pathogens, creates an ecosystem of biofilm formed by several proteins including the cyclophilins. We show that the cyclophilin peptidyl-prolyl isomerase (PpiB), an essential gene, is involved in biofilm formation and tolerance to anti-mycobacterial drugs. We predicted interaction between PpiB and US FDA approved drugs (cyclosporine-A and acarbose) by in-silico docking studies and this was confirmed by surface plasmon resonance (SPR) spectroscopy. While all these drugs inhibited growth of ( when cultured in vitro, acarbose and cyclosporine-A showed bacteriostatic effect while gallium nanoparticle (GaNP) exhibited bactericidal effect. Cyclosporine-A and GaNP additionally disrupted HRv biofilm formation. Co-culturing in their presence resulted in significant (2-4 fold) decrease in dosage of anti-tubercular drugs- isoniazid and ethambutol. Comparison of the cyclosporine-A and acarbose binding sites in PpiB homologues of other biofilm forming infectious pathogens revealed that these have largely remained unaltered across bacterial species. Targeting bacterial biofilms could be a generic strategy for intervention against bacterial pathogens.