New Quinone antibiotics against methicillin-resistant s. Aureus

Javier Campanini-Salinas; Juan Andrades-Lagos; Nicolás Hinojosa; Fabián Moreno; Pedro Alarcón; Gerardo González-Rocha; Ian E. Burbulis; David Vásquez-Velásquez

doi:10.3390/antibiotics10060614

New Quinone antibiotics against methicillin-resistant s. Aureus

Javier Campanini-Salinas^*, Juan Andrades-Lagos, Nicolás Hinojosa, Fabián Moreno, Pedro Alarcón, Gerardo González-Rocha, Ian E. Burbulis, David Vásquez-Velásquez^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC® 43300), methicillin-sensitive S. aureus (ATCC® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.

Original language	English
Article number	614
Journal	Antibiotics
Volume	10
Issue number	6
DOIs	https://doi.org/10.3390/antibiotics10060614
State	Published - 2021

Bibliographical note

Funding Information:
Funding: This research was funded by FONDECYT grant numbers 11110516 (D.V.-V.) and 79100006 (D.V.-V.).

Funding Information:
Acknowledgments: The authors gratefully acknowledge support by the Agencia Nacional de In-vestigación y Desarrollo (ANID) de Chile through a FONDECYT Iniciación en Investigación Grant No. 11110516 (D.V.-V.), Chile; FONDECYT Proyecto de Inserción Grant No. 79100006 (D.V.-V.), Chile; Programa de Estímulo a la Excelencia Institucional PEEI 2017, Universidad de Chile (D.V.-V.); and FONDECYT Regular Grant No. 1191737 (I.E.B.). The authors also gratefully acknowledge support from CONICYT de Chile in the form of a Beca Doctorados Nacional No. 21130643 (J.C.-S.) and 21130628 (J.A.-L.). The authors lastly acknowledge contributing support from the McDonnell foundation though a Fellowship from the Salk Institute (I.E.B.) and the National Institute of Allergy and Infectious Disease of the United States of America National Institutes of Health under award number NIH 7R21AI111072 (I.E.B.).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

ASJC Scopus subject areas

Microbiology
Biochemistry
General Pharmacology, Toxicology and Pharmaceutics
Microbiology (medical)
Infectious Diseases
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/antibiotics10060614

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title = "New Quinone antibiotics against methicillin-resistant s. Aureus",

abstract = "There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC{\textregistered} 43300), methicillin-sensitive S. aureus (ATCC{\textregistered} 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.",

keywords = "Drug discovery, Methicillin-resistant S. aureus (MRSA), Quinone-antibiotics",

author = "Javier Campanini-Salinas and Juan Andrades-Lagos and Nicol{\'a}s Hinojosa and Fabi{\'a}n Moreno and Pedro Alarc{\'o}n and Gerardo Gonz{\'a}lez-Rocha and Burbulis, {Ian E.} and David V{\'a}squez-Vel{\'a}squez",

note = "Funding Information: Funding: This research was funded by FONDECYT grant numbers 11110516 (D.V.-V.) and 79100006 (D.V.-V.). Funding Information: Acknowledgments: The authors gratefully acknowledge support by the Agencia Nacional de In-vestigaci{\'o}n y Desarrollo (ANID) de Chile through a FONDECYT Iniciaci{\'o}n en Investigaci{\'o}n Grant No. 11110516 (D.V.-V.), Chile; FONDECYT Proyecto de Inserci{\'o}n Grant No. 79100006 (D.V.-V.), Chile; Programa de Est{\'i}mulo a la Excelencia Institucional PEEI 2017, Universidad de Chile (D.V.-V.); and FONDECYT Regular Grant No. 1191737 (I.E.B.). The authors also gratefully acknowledge support from CONICYT de Chile in the form of a Beca Doctorados Nacional No. 21130643 (J.C.-S.) and 21130628 (J.A.-L.). The authors lastly acknowledge contributing support from the McDonnell foundation though a Fellowship from the Salk Institute (I.E.B.) and the National Institute of Allergy and Infectious Disease of the United States of America National Institutes of Health under award number NIH 7R21AI111072 (I.E.B.). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).",

year = "2021",

month = jun,

doi = "10.3390/antibiotics10060614",

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AU - Campanini-Salinas, Javier

AU - Andrades-Lagos, Juan

AU - Hinojosa, Nicolás

AU - Moreno, Fabián

AU - Alarcón, Pedro

AU - González-Rocha, Gerardo

AU - Burbulis, Ian E.

AU - Vásquez-Velásquez, David

N1 - Funding Information: Funding: This research was funded by FONDECYT grant numbers 11110516 (D.V.-V.) and 79100006 (D.V.-V.). Funding Information: Acknowledgments: The authors gratefully acknowledge support by the Agencia Nacional de In-vestigación y Desarrollo (ANID) de Chile through a FONDECYT Iniciación en Investigación Grant No. 11110516 (D.V.-V.), Chile; FONDECYT Proyecto de Inserción Grant No. 79100006 (D.V.-V.), Chile; Programa de Estímulo a la Excelencia Institucional PEEI 2017, Universidad de Chile (D.V.-V.); and FONDECYT Regular Grant No. 1191737 (I.E.B.). The authors also gratefully acknowledge support from CONICYT de Chile in the form of a Beca Doctorados Nacional No. 21130643 (J.C.-S.) and 21130628 (J.A.-L.). The authors lastly acknowledge contributing support from the McDonnell foundation though a Fellowship from the Salk Institute (I.E.B.) and the National Institute of Allergy and Infectious Disease of the United States of America National Institutes of Health under award number NIH 7R21AI111072 (I.E.B.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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N2 - There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC® 43300), methicillin-sensitive S. aureus (ATCC® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.

AB - There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC® 43300), methicillin-sensitive S. aureus (ATCC® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.

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ER -

New Quinone antibiotics against methicillin-resistant s. Aureus

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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