Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a pervasive and persistent threat that requires the development of novel therapies or adjuvants for existing ones. Aptamers, small single-stranded oligonucleotides that form 3D structures and can bind to target molecules, provi...

Descrición completa

Detalles Bibliográficos
Main Authors: Matthew K. Doherty, Claire Shaw, Leslie Woods, Bart C. Weimer
Formato: Artigo
Idioma:English
Publicado: MDPI AG 2023-07-01
Series:Microorganisms
Subjects:
Acceso en liña:https://www.mdpi.com/2076-2607/11/7/1776
_version_ 1827732286907351040
author Matthew K. Doherty
Claire Shaw
Leslie Woods
Bart C. Weimer
author_facet Matthew K. Doherty
Claire Shaw
Leslie Woods
Bart C. Weimer
author_sort Matthew K. Doherty
collection DOAJ
description Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a pervasive and persistent threat that requires the development of novel therapies or adjuvants for existing ones. Aptamers, small single-stranded oligonucleotides that form 3D structures and can bind to target molecules, provide one possible therapeutic route, especially when presented in combination with current antibiotic applications. BALB/c α-1, 3-galactosyltransferase (−/−) knockout (GTKO) mice were infected with MRSA via tail vein IV and subsequently treated with the αSA31 aptamer (n = 4), vancomycin (n = 12), or αSA31 plus vancomycin (n = 12), with split doses in the morning and evening. The heart, lungs, liver, spleen, and kidneys were harvested upon necropsy for histological and qPCR analysis. All mice treated with αSA31 alone died, whereas 5/12 mice treated with vancomycin alone and 7/12 mice treated with vancomycin plus αSA31 survived the course of the experiment. The treatment of MRSA-infected mice with Vancomycin and an adjuvant aptamer αSA31 reduced disease persistence and dispersion as compared to treatment with either vancomycin SA31 alone, indicating the combination of antibiotic and specifically targeted αSA31 aptamer could be a novel way to control MRSA infection. The data further indicate that aptamers may serve as a potential therapeutic option for other emerging antibiotic resistant pathogens.
first_indexed 2024-03-11T00:49:25Z
format Article
id doaj.art-fd7b4829c29b4b45b295d6b0e0d9d20a
institution Directory Open Access Journal
issn 2076-2607
language English
last_indexed 2024-03-11T00:49:25Z
publishDate 2023-07-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj.art-fd7b4829c29b4b45b295d6b0e0d9d20a2023-11-18T20:36:17ZengMDPI AGMicroorganisms2076-26072023-07-01117177610.3390/microorganisms11071776Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In VivoMatthew K. Doherty0Claire Shaw1Leslie Woods2Bart C. Weimer3Population Health and Reproduction, University of California Davis, Davis, CA 95616, USAPopulation Health and Reproduction, University of California Davis, Davis, CA 95616, USACalifornia Animal Health and Food Safety Laboratory, University of California Davis, Davis, CA 95616, USAPopulation Health and Reproduction, University of California Davis, Davis, CA 95616, USAMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a pervasive and persistent threat that requires the development of novel therapies or adjuvants for existing ones. Aptamers, small single-stranded oligonucleotides that form 3D structures and can bind to target molecules, provide one possible therapeutic route, especially when presented in combination with current antibiotic applications. BALB/c α-1, 3-galactosyltransferase (−/−) knockout (GTKO) mice were infected with MRSA via tail vein IV and subsequently treated with the αSA31 aptamer (n = 4), vancomycin (n = 12), or αSA31 plus vancomycin (n = 12), with split doses in the morning and evening. The heart, lungs, liver, spleen, and kidneys were harvested upon necropsy for histological and qPCR analysis. All mice treated with αSA31 alone died, whereas 5/12 mice treated with vancomycin alone and 7/12 mice treated with vancomycin plus αSA31 survived the course of the experiment. The treatment of MRSA-infected mice with Vancomycin and an adjuvant aptamer αSA31 reduced disease persistence and dispersion as compared to treatment with either vancomycin SA31 alone, indicating the combination of antibiotic and specifically targeted αSA31 aptamer could be a novel way to control MRSA infection. The data further indicate that aptamers may serve as a potential therapeutic option for other emerging antibiotic resistant pathogens.https://www.mdpi.com/2076-2607/11/7/1776antimicrobialMRSAaptamer antibioticantimicrobial resistancesepsis
spellingShingle Matthew K. Doherty
Claire Shaw
Leslie Woods
Bart C. Weimer
Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
Microorganisms
antimicrobial
MRSA
aptamer antibiotic
antimicrobial resistance
sepsis
title Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
title_full Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
title_fullStr Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
title_full_unstemmed Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
title_short Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce <i>Staphylococcus aureus</i> Infection In Vivo
title_sort alpha gal bound aptamer and vancomycin synergistically reduce i staphylococcus aureus i infection in vivo
topic antimicrobial
MRSA
aptamer antibiotic
antimicrobial resistance
sepsis
url https://www.mdpi.com/2076-2607/11/7/1776
work_keys_str_mv AT matthewkdoherty alphagalboundaptamerandvancomycinsynergisticallyreduceistaphylococcusaureusiinfectioninvivo
AT claireshaw alphagalboundaptamerandvancomycinsynergisticallyreduceistaphylococcusaureusiinfectioninvivo
AT lesliewoods alphagalboundaptamerandvancomycinsynergisticallyreduceistaphylococcusaureusiinfectioninvivo
AT bartcweimer alphagalboundaptamerandvancomycinsynergisticallyreduceistaphylococcusaureusiinfectioninvivo