Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters

Chemotherapy is frequently unsuccessful in fully eradicating bacterial biofilm infections. Persisters are a main cause for the failure of antibiotic therapies and are assumed to significantly impact the increased multidrug tolerance and unsuccessful elimination of chronic biofilm infections. Pseudom...

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Main Authors: L.B. Al Husseini, A. Maleki, M.F. Al Marjani
Format: Article
Language:English
Published: Elsevier 2021-05-01
Series:New Microbes and New Infections
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2052297521000329
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author L.B. Al Husseini
A. Maleki
M.F. Al Marjani
author_facet L.B. Al Husseini
A. Maleki
M.F. Al Marjani
author_sort L.B. Al Husseini
collection DOAJ
description Chemotherapy is frequently unsuccessful in fully eradicating bacterial biofilm infections. Persisters are a main cause for the failure of antibiotic therapies and are assumed to significantly impact the increased multidrug tolerance and unsuccessful elimination of chronic biofilm infections. Pseudomonas aeruginosa infections are frequently linked to high rates of drug-tolerant persisters, triggering a major challenge to human health. It is crucial to classify persisters to develop novel useful therapeutic strategies to fight infectious diseases. In this study, the mqsR gene was selected as a novel antimicrobial target, and silencing was with antisense peptide nucleic acid (PNA) assay to eradicate the P. aeruginosa persisters. First, they were analysed by experimental procedures. Functionality was assessed by stress conditions. We found that the expression of mqsR (as the toxin) compared with mqsA (as antitoxin) was increased under stress conditions. We demonstrated that when mqsR was targeted and treated with different concentrations of mqsR-PNA after 24 hours; the formation of P. aeruginosa persisters was eradicated. Antisense mqsR-PNA in concentrations of 35 μM or more could eradicate persister cell formation in P. aeruginosa. It was suggested that other toxin–antitoxin loci in P. aeruginosa are examined by antisense PNA to detect their functionality. However, considering the importance of persisters in human infections, ex vivo, in vivo, preclinical and clinical settings should be highlighted.
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spelling doaj.art-4cf7c31a753f47dea9941260d1cd20612022-12-21T22:23:19ZengElsevierNew Microbes and New Infections2052-29752021-05-0141100868Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persistersL.B. Al Husseini0A. Maleki1M.F. Al Marjani2Department of Biology, College of Science, Mustansiriyah University, Baghdad, IraqClinical Microbiology Research Centre, Ilam University of Medical Sciences, Ilam, IranDepartment of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq; Corresponding author: M.F. Al Marjani, Mustansiriyah University, Palestine Street, P.O.Box: 10052, Baghdad, Iraq.Chemotherapy is frequently unsuccessful in fully eradicating bacterial biofilm infections. Persisters are a main cause for the failure of antibiotic therapies and are assumed to significantly impact the increased multidrug tolerance and unsuccessful elimination of chronic biofilm infections. Pseudomonas aeruginosa infections are frequently linked to high rates of drug-tolerant persisters, triggering a major challenge to human health. It is crucial to classify persisters to develop novel useful therapeutic strategies to fight infectious diseases. In this study, the mqsR gene was selected as a novel antimicrobial target, and silencing was with antisense peptide nucleic acid (PNA) assay to eradicate the P. aeruginosa persisters. First, they were analysed by experimental procedures. Functionality was assessed by stress conditions. We found that the expression of mqsR (as the toxin) compared with mqsA (as antitoxin) was increased under stress conditions. We demonstrated that when mqsR was targeted and treated with different concentrations of mqsR-PNA after 24 hours; the formation of P. aeruginosa persisters was eradicated. Antisense mqsR-PNA in concentrations of 35 μM or more could eradicate persister cell formation in P. aeruginosa. It was suggested that other toxin–antitoxin loci in P. aeruginosa are examined by antisense PNA to detect their functionality. However, considering the importance of persisters in human infections, ex vivo, in vivo, preclinical and clinical settings should be highlighted.http://www.sciencedirect.com/science/article/pii/S2052297521000329Eradicationpeptide nucleic acid assaypersister cellsPseudomonas aeruginosaTA system
spellingShingle L.B. Al Husseini
A. Maleki
M.F. Al Marjani
Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
New Microbes and New Infections
Eradication
peptide nucleic acid assay
persister cells
Pseudomonas aeruginosa
TA system
title Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
title_full Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
title_fullStr Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
title_full_unstemmed Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
title_short Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters
title_sort antisense mqsr pna as a putative target to the eradication of pseudomonas aeruginosa persisters
topic Eradication
peptide nucleic acid assay
persister cells
Pseudomonas aeruginosa
TA system
url http://www.sciencedirect.com/science/article/pii/S2052297521000329
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AT amaleki antisensemqsrpnaasaputativetargettotheeradicationofpseudomonasaeruginosapersisters
AT mfalmarjani antisensemqsrpnaasaputativetargettotheeradicationofpseudomonasaeruginosapersisters