Our group recently published an article, co-authored by Dr. Swagatam Barman, Ms. Geetika Dhanda, Ms. Poonam Naik, Dr. Riya Mukherjee, Ms. Logia Jolly, Dr. Joveeta Joseph and Prof. Jayanta Haldar. The work is a result of collaborative research with Dr. Joveeta Joseph and her group from L. V. Prasad Eye Institute, Hyderabad.
This new class of multi-functional amino acid conjugated small antibacterial molecules (ASAMs) exhibit broad-spectrum bactericidal activity against multi-drug-resistant bacteria. The phenylalanine-bearing lead molecule (ASAM-10) tackles bacterial dormant subpopulations, impenetrable biofilms, and intracellular pathogens simultaneously. Importantly, this molecule addresses the problem of toxicity associated with cationic lipopeptides like colistin through the temporal charge switching (cationic to zwitterionic) owing to the degradation of labile ester linkages. However, this does not affect its desired antibacterial action window. The substantial reduction in the overexpression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, and IL-1β) upon treatment of infected macrophages with ASAM-10 validates its anti-inflammatory efficacy. Furthermore, bacteria exhibit diminished susceptibility toward resistance development against ASAM-10 owing to its membrane-active nature. ASAM-10 displays significant reduction in bacterial burden (2 Log CFU/g) when administered intraperitoneally in mice for MRSA thigh infection. Overall, this new class of multi-functional molecules is safe for anticipated advanced therapeutic applications to combat complex bacterial infections and inflammation.
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