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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Format: | Article |
Language: | English |
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Elsevier
2021-05-01
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Series: | New Microbes and New Infections |
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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. |
first_indexed | 2024-12-16T17:14:54Z |
format | Article |
id | doaj.art-4cf7c31a753f47dea9941260d1cd2061 |
institution | Directory Open Access Journal |
issn | 2052-2975 |
language | English |
last_indexed | 2024-12-16T17:14:54Z |
publishDate | 2021-05-01 |
publisher | Elsevier |
record_format | Article |
series | New Microbes and New Infections |
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 |
work_keys_str_mv | AT lbalhusseini antisensemqsrpnaasaputativetargettotheeradicationofpseudomonasaeruginosapersisters AT amaleki antisensemqsrpnaasaputativetargettotheeradicationofpseudomonasaeruginosapersisters AT mfalmarjani antisensemqsrpnaasaputativetargettotheeradicationofpseudomonasaeruginosapersisters |