Researchers at the Indian Institute of Technology (IIT) Roorkee have discovered a critical regulatory mechanism in the extremely drug-resistant superbug Acinetobacter baumannii, which causes infections that can be fatal.

Their research, which was published in the journal mBio, opens the door to new treatment approaches by illuminating how the pathogen regulates its defense and attack mechanisms.

Acinetobacter baumannii poses a serious threat in healthcare settings as it resists multiple antibiotics. It causes severe hospital-acquired infections, including pneumonia, bloodstream infections, and urinary tract infections.

To attack competing microbes, the superbug uses the Type 6 Secretion System (T6SS) -- a bacterial "weapon". However, its mechanism for maintaining antibiotic resistance has remained unclear until now.

The research team, led by Prof. Ranjana Pathania, discovered that A. baumannii switches T6SS on or off based on environmental conditions. They found that a small RNA molecule -- AbsR28 -- plays a key role in this regulation, influenced by manganese levels.

When manganese levels are high, AbsR28 binds to an essential gene (tssM) required for T6SS function. This not only leads to its degradation but also prevents the activation of T6SS, said the researchers.

Increased manganese levels also enable A. baumannii to retain plasmid pAB3, which carries multiple antibiotic-resistance genes.

“We found that when A. baumannii activates T6SS, it becomes more vulnerable to antibiotics and oxidative stress. So, the bacteria must carefully regulate this system to survive in different conditions,” said Prof. Pathania.

“Our discovery sheds light on how this pathogen adapts during infections, helping it evade both antibiotics and the immune system,” she added.

The findings showed that targeting AbsR28 can help disrupt the superbug’s regulatory system. This makes it more susceptible to antibiotics without directly attacking resistance genes. The discovery also opens new avenues for precision medicine and novel drug development against multidrug-resistant infections.