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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.03117-19 |
| _version_ | 1819203108715102208 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T04:14:41Z |
| format | Article |
| id | doaj.art-9abd35338e1c41eb8ed007a1e04e4846 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-23T04:14:41Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-9abd35338e1c41eb8ed007a1e04e48462022-12-21T18:00:24ZengAmerican Society for MicrobiologymBio2150-75112020-02-0111110.1128/mBio.03117-19Cryo-electron Microscopy Structure of the <named-content content-type="genus-species">Acinetobacter baumannii</named-content> 70S Ribosome and Implications for New Antibiotic DevelopmentChristopher E. Morgan0Wei Huang1Susan D. Rudin2Derek J. Taylor3James E. Kirby4Robert A. Bonomo5Edward W. Yu6Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USALouis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USADepartment of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.03117-1970S ribosomeAcinetobacter baumanniicryo-EMantibiotic resistancestructural biology |
| spellingShingle | 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 mBio 70S ribosome Acinetobacter baumannii cryo-EM antibiotic resistance structural biology |
| 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_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_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_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 |
| topic | 70S ribosome Acinetobacter baumannii cryo-EM antibiotic resistance structural biology |
| url | https://journals.asm.org/doi/10.1128/mBio.03117-19 |
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