Researchers at Indian Institute of Technology (IIT) Roorkee have identified a protein (Hfq) in Acinetobacter baumannii bacteria that can be a potential drug target. The Hfq protein plays an important role in metabolism, drug resistance, stress tolerance and virulence. The protein stabilises the interaction of small RNA with its target mRNA molecules.
A. baumannii bacteria are resistant to several antibiotics. They also survive in dry, desiccated conditions for extended periods thus helping the bacteria spread.
While most Gram-negative bacteria have Hfq protein, the protein is particularly long in the case of A. baumannii. For instance, In E. coli, the length of the Hfq protein is only about 100 amino acids while there are 168 amino acids in the case of A. baumannii . The end of the Hfq protein, called the C-terminus is what is particularly long in A. baumannii. While another study had reported that the extra length of the C-terminus may not be significant in another bacteria belonging to the same family as A. baumannii, the team found evidence to the contrary.
The team led by Ranjana Pathania from the Institute’s Department of Biotechnology found that when the Hfq gene was removed (knocked out), the bacteria became susceptible to environmental stress, showed stunted growth, survival under desiccation was compromised, and the ability to form biofilm was reduced. “But most importantly, the virulence of the bacteria was significantly reduced in mice model infected with the mutant bacteria,” says Prof. Pathania. The results of the study were published in The Journal of Biological Chemistry.
To reconfirm the role of the extra length of Hfq protein, the researchers complemented or added the full length of the protein and also Hfq protein of different lengths (66, 72 and 92 amino acids). “While the full length of the complemented protein could restore all the functions and processes, including virulence, the Hfq protein lacking the C-terminus tail could not restore the functions of the protein. So it became apparent that the C-terminus tail is important,” she says.
The resistance to two commonly used antibiotics reduced twofold when the bacteria lacked the Hfq gene, but the resistance increased nearly fourfold in the case of another antibiotic. “We are currently studying the mechanism by which the resistance increases in the case of the other drug (Meropenem),” she says.
More than the gene’s role in altering drug resistance, the researchers are thrilled at how removing the Hfq gene causes the bacteria to lose its ability to cause disease and the growth getting compromised. “Targeting the virulence of the bacteria is a rather new concept which promises drugs that don’t lead to rapid generation of resistance. Identification of Hfq as a virulence factor in the bacteria opens up a new opportunity to develop more effective drugs,” says Prof. Pathania.
“Since the Hfq gene controls multiple pathways in the bacteria, it will be difficult for the bacteria to develop resistance against any drug that targets this gene,” says Prof. Pathania.
