Hyderabad scientists link bacterial cell wall mechanism to potential human health benefits

Hyderabad: A team of scientists led by Dr. Manjula Reddy at the CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, has discovered a novel proofreading step that ensures the strength and integrity of bacterial cell walls.

The findings, published in the Proceedings of the National Academy of Sciences (PNAS), could provide new clues for improving antibiotic therapies and understanding immune disorders in humans.

Bacterial cell walls are composed of peptidoglycan, a polymer made up of sugars and short amino acid chains, including L-alanine. The study reveals that bacteria sometimes mistakenly incorporate structurally similar amino acids such as L-serine or glycine instead of L-alanine. These mistakes weaken the cell wall, making the bacteria more vulnerable to antibiotics.

Dr. Reddy’s team identified an enzyme, PgeF (Peptidoglycan Editing Factor), that corrects these errors during cell wall synthesis. “Using a combination of genetics and high-resolution mass spectrometry, we observed that PgeF specifically detects and removes the incorrect amino acids to preserve the composition of the cell wall,” said Dr. Shambhavi Garde, the study’s first author.

The discovery also opens new research directions. “By studying such vulnerabilities in cell wall synthesis, new ways of blocking bacterial growth could be developed. What makes the discovery more interesting is that a homolog of this enzyme exists in vertebrates, including humans. Defects in this enzyme, known as LACC1, are associated with several autoinflammatory disorders, where the immune system is overactive,” said Dr. Reddy.

Though the exact role of LACC1 in humans remains unclear, this study suggests it may be involved in immune responses to bacterial infections, offering potential avenues for therapeutic strategies in the future.