A new component that can weakly disrupt the bacterial membrane and thus counter bacterial resistance to multiple classes of antibiotics may help restore the effectiveness of outdated antibiotics. This strategy can fight the most critical group of bacteria and allows to reuse the existing antibiotic arsenal for complicated infections. It can help counter the growing threat of antimicrobial resistance.
The World Health Organization has identified Acineto bacterbaumannii, Pseudomonas aeruginosa and Enterobacteriaceae, all of which are resistant to carbapenems, as the highest priority critical pathogens. There are several treatment options for these bacteria, triggering the use of combinations of different antibiotics to treat such complicated infections. It was therefore appropriate to develop new unconventional therapeutic strategies to deal with these pathogens.
Scientists from JNCASR, an autonomous institute of the Department of Science and Technology, have come up with an approach to revitalize the effectiveness of existing antibiotics by using them in combination with antibiotic adjuvants – ingredients that can help counter resistance to existing antibiotics. This new idea may help boost the activity of outdated antibiotics and bring them back into use to treat complicated infections.
Ms. Geetika Dhanda and Prof. Jayanta Haldar incorporated cyclic hydrophobic moieties (a part of the molecule) into a triamine-containing compound, the thus developed adjuvant weakly disrupted the bacterial membrane. This led to suppression of membrane-related elements of resistance such as the permeability barrier and expulsion of antibiotics by efflux pumps. When these adjuvants are used in combination with antibiotics rendered ineffective by such membrane-associated resistance elements, the antibiotics are potentiated and the combination is effective in killing the bacteria.
The combination of adjuvants with antibiotics such as fusidic acid, minocycline and rifampicin inactivates multidrug-resistant gram-negative bacteria. These include Acineto bacterbaumannii, Pseudomonas aeruginosa and Entero bacteriaceae. The study, published in the journal ACS Infect. Diseases, emphasize the chemical intuition and extent of membrane disruption required for the design of inactive and nontoxic adjuvants. Choosing an inactive adjuvant would also put less pressure on bacteria to develop resistance to it. Furthermore, weak membrane perturbation would result in less toxicity.
