Abstract
Antimicrobial resistance is a major health threat as it limits treatment options for infection. At the forefront of this serious issue is Acinetobacter baumannii, a Gram-negative opportunistic pathogen that exhibits the remarkable ability to resist antibiotics through multiple mechanisms. As bacterial ribosomes represent a target for multiple distinct classes of existing antimicrobial agents, we here use single-particle cryo-electron microscopy (cryo-EM) to elucidate five different structural states of the A. baumannii ribosome, including the 70S, 50S, and 30S forms. We also determined interparticle motions of the 70S ribosome in different tRNA bound states using three-dimensional (3D) variability analysis. Together, our structural data further our understanding of the ribosome from A. baumannii and other Gram-negative pathogens and will enable structure-based drug discovery to combat antibiotic-resistant bacterial infections.IMPORTANCEAcinetobacter baumannii is a severe nosocomial threat largely due to its intrinsic antibiotic resistance and remarkable ability to acquire new resistance determinants. The bacterial ribosome serves as a major target for modern antibiotics and the design of new therapeutics. Here, we present cryo-EM structures of the A. baumannii 70S ribosome, revealing several unique species-specific structural features that may facilitate future drug development to combat this recalcitrant bacterial pathogen.
Highlights
Antimicrobial resistance is a major health threat as it limits treatment options for infection
The ribosome represents a major target for antimicrobial agents as it is vital for protein synthesis and is one of the largest molecular machines in the cell [1]
Exploration of ribosome structure and function in a species of great clinical concern will allow us to define new targets for ribosome engagement and in turn enable discovery of novel therapeutic strategies to combat multidrug-resistant pathogens like Acinetobacter baumannii
Summary
Antimicrobial resistance is a major health threat as it limits treatment options for infection. We report cryo-electron microscopy (cryo-EM) structures of three different conformational states of the A. baumannii 70S ribosome at resolutions between 2.82 and 3.04 Å. The first three classes depict structures of the mature 70S ribosome in the absence and presence of a tRNA molecule occupying the P or E site (Fig. 2).
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