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A Single Amino Acid Substitution in Elongation Factor G Can Confer Low-Level Gentamicin Resistance in Neisseria gonorrhoeae

Holley, Concerta L. (författare)
Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
Dhulipala, Vijaya (författare)
Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
Balthazar, Jacqueline T. (författare)
Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
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Le Van, Adriana (författare)
Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, USA
Begum, Afrin A. (författare)
Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, USA
Chen, Shao-Chun (författare)
Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China; National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People's Republic of China
Read, Timothy D. (författare)
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; The Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
Matoga, Mitch (författare)
UNC Project Malawi, Lilongwe, Malawi
Hoffman, Irving F. (författare)
Department of Medicine, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA
Golparian, Daniel, 1984- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology
Unemo, Magnus, 1970- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Institute for Global Health, University College London, London, United Kingdom
Jerse, Ann E. (författare)
Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, USA
Shafer, William M. (författare)
Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; The Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, Georgia, USA
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Department of Microbiology and Immunology, Emory University School of Medicinegrid471395.d, Atlanta, Georgia, USA Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, USA (creator_code:org_t)
American Society for Microbiology, 2022
2022
Engelska.
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 66:5
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • The continued emergence of Neisseria gonorrhoeae isolates which are resistant to first-line antibiotics has reinvigorated interest in alternative therapies such as expanded use of gentamicin (Gen). We hypothesized that expanded use of Gen promotes emergence of gonococci with clinical resistance to this aminoglycoside. To understand how decreased susceptibility of gonococci to Gen might develop, we selected spontaneous low-level Gen-resistant (GenR) mutants (Gen MIC = 32 μg/mL) of the Gen-susceptible strain FA19. Consequently, we identified a novel missense mutation in fusA, which encodes elongation factor G (EF-G), causing an alanine (A) to valine (V) substitution at amino acid position 563 in domain IV of EF-G; the mutant allele was termed fusA2. Transformation analysis showed that fusA2 could increase the Gen MIC by 4-fold. While possession of fusA2 did not impair either in vitro gonococcal growth or protein synthesis, it did result in a fitness defect during experimental infection of the lower genital tract in female mice. Through bioinformatic analysis of whole-genome sequences of 10,634 international gonococcal clinical isolates, other fusA alleles were frequently detected, but genetic studies revealed that they could not decrease Gen susceptibility in a similar manner to fusA2. In contrast to these diverse international fusA alleles, the fusA2-encoded A563V substitution was detected in only a single gonococcal clinical isolate. We hypothesize that the rare occurrence of fusA2 in N. gonorrhoeae clinical isolates is likely due to a fitness cost during infection, but compensatory mutations which alleviate this fitness cost could emerge and promote GenR in global strains.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Nyckelord

Neisseria gonorrhoeae
fusA
gentamicin
resistance
spontaneous mutant

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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