Schematic explaining the working of the antiseptic analogue. Credit: IISER Pune & CDRI
A new analogue of diphenyleneiodonium (dPI), an antiseptic, can kill carbapenem-resistant Acinetobacter baumannii (CRAB), which is on the World Health Organization’s priority pathogens list1.
A. baumannii, a Gram-negative pathogen, is one of the six most deadly multidrug-resistant (MDR) pathogens for which new antibiotics are urgently needed. It causes pneumonia, meningitis, wound and surgical site infections, and urinary tract infections, especially common among people who are critically ill or immunocompromised.
A. baumannii infections are extremely difficult to treat and multidrug resistance makes it even more difficult.
Scientists at CSIR-Central Drug Research Institute, Lucknow, and the Indian Institute of Science Education and Research Pune, synthesized and screened iodonium salt analogues and identified analogue 3a, which substantially reduced the bacterial burden in an animal model. “The analogue can potentially kill many Gram-negative bacteria but shows the highest potency towards drug-resistant A. baumannii clinical strains,” says co-author Siddhesh Kamat.
Using mass spectrometry-based chemoproteomic platforms, the study also pinpointed betaine aldehyde dehydrogenase — an enzyme involved in the metabolism and maintenance of osmolarity in the pathogen — as the analogue’s potential target.
Co-author Harinath Chakrapani says the enzymes or proteins could become the basis for new drug discovery.
When used in combination with amikacin, the antibiotic currently used to treat A. baumannii infections, the new analogue also enhanced the antibiotic’s potency without inducing resistance.
The team is now working to enhance the ability of the new analogue to be better absorbed and used in humans.
