Scientists image the molecular pump that lets bacteria shrug off antibiotics
Antibiotic resistance is one of medicine’s most pressing threats — and one of bacteria’s cleverest tricks is simply pumping drugs back out before they can do any harm.
When bacteria encounter an antibiotic, they have several survival strategies. They can chemically degrade the drug, modify their cell wall to block entry, or deploy a molecular pump that actively expels the antibiotic before it reaches its target. That last strategy — carried out by so-called efflux pumps — is widespread and one of the primary drivers of multidrug resistance in bacteria like Escherichia coli.
A study published in eLife has now resolved the three-dimensional structure of the AcrAB-TolC efflux system in E. coli at near-atomic resolution, using cryo-electron microscopy — a technique that freezes proteins and bombards them with electrons to reconstruct their precise shape. The result is two detailed structures: a subcomplex of TolC and the previously uncharacterized protein YbjP, and the complete pump assembly.
An unknown protein with a critical role
The discovery of YbjP stands out. This lipoprotein — a protein anchored in the bacterial membrane — was almost entirely uncharacterized before this study. The new structures show that it plays an essential bridging role in the pump mechanism, connecting TolC units in a way that determines the stability and function of the entire complex. Without YbjP, the pump falls apart.
The structures also reveal, for the first time, how drug molecules move through the pump channel — an insight that had eluded researchers for years. That gives scientists a concrete target for designing molecules that block the pump itself, rather than simply trying to make antibiotics more potent.
A new target in the resistance fight
The therapeutic implication is direct: block the pump, and bacteria become sensitive again to antibiotics they would otherwise expel without consequence. So-called efflux pump inhibitors have been studied as adjuncts to existing antibiotics for decades, but results have been disappointing — partly because the mechanics of the pumps were poorly understood. A precise structure changes the starting point for that search entirely.
This is not a solution available tomorrow. Moving from structure to functional inhibitor requires extensive chemical optimization, toxicity testing, and clinical trials. But in a field where the antibiotic pipeline has run dangerously dry, any new molecular foothold matters — especially as drug-resistant infections now claim more lives globally each year than HIV.