Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 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 Acinetobacter baumannii, a Gram-negative opportunistic pathogen that exhibits the remarkable ability to resist antibiotics through multiple mechanisms. A...

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Autores principales:	Christopher E. Morgan, Wei Huang, Susan D. Rudin, Derek J. Taylor, James E. Kirby, Robert A. Bonomo, Edward W. Yu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	70S ribosome Acinetobacter baumannii cryo-EM antibiotic resistance structural biology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9abd35338e1c41eb8ed007a1e04e4846
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spelling	oai:doaj.org-article:9abd35338e1c41eb8ed007a1e04e48462021-11-15T15:56:58ZCryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development10.1128/mBio.03117-192150-7511https://doaj.org/article/9abd35338e1c41eb8ed007a1e04e48462020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03117-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Acinetobacter 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.Christopher E. MorganWei HuangSusan D. RudinDerek J. TaylorJames E. KirbyRobert A. BonomoEdward W. YuAmerican Society for Microbiologyarticle70S ribosomeAcinetobacter baumanniicryo-EMantibiotic resistancestructural biologyMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	70S ribosome Acinetobacter baumannii cryo-EM antibiotic resistance structural biology Microbiology QR1-502
spellingShingle	70S ribosome Acinetobacter baumannii cryo-EM antibiotic resistance structural biology Microbiology QR1-502 Christopher E. Morgan Wei Huang Susan D. Rudin Derek J. Taylor James E. Kirby Robert A. Bonomo Edward W. Yu Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
description	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. IMPORTANCE Acinetobacter 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.
format	article
author	Christopher E. Morgan Wei Huang Susan D. Rudin Derek J. Taylor James E. Kirby Robert A. Bonomo Edward W. Yu
author_facet	Christopher E. Morgan Wei Huang Susan D. Rudin Derek J. Taylor James E. Kirby Robert A. Bonomo Edward W. Yu
author_sort	Christopher E. Morgan
title	Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
title_short	Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
title_full	Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
title_fullStr	Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
title_full_unstemmed	Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development
title_sort	cryo-electron microscopy structure of the <named-content content-type="genus-species">acinetobacter baumannii</named-content> 70s ribosome and implications for new antibiotic development
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9abd35338e1c41eb8ed007a1e04e4846
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Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic Development

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