Cryo-electron Microscopy Structure of the Acinetobacter baumannii 70S Ribosome and Implications for New Antibiotic Development

Abstract

Antimicrobial resistance is a major health threat as it limits treatment options for infection. At the forefront of this serious issue is <i>Acinetobacter baumannii</i>, 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 <i>A. baumannii</i> 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 <i>A. baumannii</i> and other Gram-negative pathogens and will enable structure-based drug discovery to combat antibiotic-resistant bacterial infections.<b>IMPORTANCE</b><i>Acinetobacter baumannii</i> 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 <i>A. baumannii</i> 70S ribosome, revealing several unique species-specific structural features that may facilitate future drug development to combat this recalcitrant bacterial pathogen.