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High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa

Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573...

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Autores principales: Li, Shijia, She, Pengfei, Zhou, Linying, Zeng, Xianghai, Xu, Lanlan, Liu, Yaqian, Chen, Lihua, Wu, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755642/
https://www.ncbi.nlm.nih.gov/pubmed/33362739
http://dx.doi.org/10.3389/fmicb.2020.591426
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author Li, Shijia
She, Pengfei
Zhou, Linying
Zeng, Xianghai
Xu, Lanlan
Liu, Yaqian
Chen, Lihua
Wu, Yong
author_facet Li, Shijia
She, Pengfei
Zhou, Linying
Zeng, Xianghai
Xu, Lanlan
Liu, Yaqian
Chen, Lihua
Wu, Yong
author_sort Li, Shijia
collection PubMed
description Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against Pseudomonas aeruginosa. A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of P. aeruginosa while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on P. aeruginosa PAO1 and P. aeruginosa ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) P. aeruginosa strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR P. aeruginosa-related infections.
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spelling pubmed-77556422020-12-24 High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa Li, Shijia She, Pengfei Zhou, Linying Zeng, Xianghai Xu, Lanlan Liu, Yaqian Chen, Lihua Wu, Yong Front Microbiol Microbiology Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against Pseudomonas aeruginosa. A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of P. aeruginosa while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on P. aeruginosa PAO1 and P. aeruginosa ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) P. aeruginosa strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR P. aeruginosa-related infections. Frontiers Media S.A. 2020-12-09 /pmc/articles/PMC7755642/ /pubmed/33362739 http://dx.doi.org/10.3389/fmicb.2020.591426 Text en Copyright © 2020 Li, She, Zhou, Zeng, Xu, Liu, Chen and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Li, Shijia
She, Pengfei
Zhou, Linying
Zeng, Xianghai
Xu, Lanlan
Liu, Yaqian
Chen, Lihua
Wu, Yong
High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title_full High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title_fullStr High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title_full_unstemmed High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title_short High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
title_sort high-throughput identification of antibacterials against pseudomonas aeruginosa
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755642/
https://www.ncbi.nlm.nih.gov/pubmed/33362739
http://dx.doi.org/10.3389/fmicb.2020.591426
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