The antibiotic resistance crisis among Gram-negative bacterial pathogens

Gram-negative pathogens now contribute to more than 1 million global deaths due to antibiotic resistance, with Escherichia coli responsible for the most deaths. No new class of antibiotic against Gram-negative bacteria has been introduced into the clinic since the 1970s. In the meantime, resistance to available antibiotics has become more common. Some pathogens are resistant to almost all antibiotics.

The defining feature of Gram-negative bacteria is a double membrane cell architecture. The outer membrane (OM) forms the cell’s surface and represents the frontline in the battle between a pathogen and its host. The OM is a barrier that shields the bacterial cell against assaults from the immune system and antibiotics. By preventing antibiotics from reaching their intracellular targets, the OM provides a highly potent intrinsic antibiotic resistance mechanism that is shared among Gram-negative pathogens.

Our group uses genetics, high-throughput DNA sequencing approaches, biochemistry, and molecular biology to dissect the essential mechanisms that bacteria rely on to build their OM barrier, monitor its integrity, and remodel it during infection. We work among evolutionarily diverse Gram-negative bacterial species including Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and others.

The goal of our work is to shed light on how the OM is built and maintained. Our discoveries enable more rational and sophisticated approaches to developing much needed novel antibiotics that can kill Gram-negative pathogens.