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Antibiotics
Special Issues
Antibiotic Tolerance in Pseudomonas aeruginosa
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Antibiotic Tolerance in Pseudomonas aeruginosa

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 6610

Special Issue Editors

Prof. Dr. Keiji Murakami

E-Mail Website
Guest Editor
Department of Clinical Nutrition, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki 701-0193, Japan
Interests: microbiology; infectious diseases; biofilm; mechanisms of antibiotic resistance and tolerance; quorum sensing
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Yukihiro Kaneko

E-Mail Website
Guest Editor
Department of Bacteriology, Graduate School of Medicine, Osaka City University, Osaka, Japan
Interests: intractable bacterial infection; antimicrobial resistance

Special Issue Information

Dear Colleagues,

Pseudomonas aeruginosa is an opportunistic pathogen commonly associated with chronic and refractory infections due to its ability to form biofilms. Antibiotic tolerance, which is regarded as the ability of bacteria to survive, but not grow, in the presence of antibiotics, has attracted attention as a cause of chronic infectious diseases. Antibiotic tolerance is a physiological condition that appears with a certain probability without any gene mutations. In biofilms, increasing the population of persister cells, which are dormant and nondividing, contributes to antibiotic tolerance. The elucidation of the molecular mechanisms responsible for antibiotic tolerance could lead to the discovery of potential targets for new antimicrobial agents.

The main objective of this Special Issue is to attract original research and review articles covering concepts and investigations regarding antibiotic tolerance. We hope that this Special Issue will also highlight new therapeutic strategies for P. aeruginosa chronic infections.

Prof. Dr. Keiji Murakami
Prof. Dr. Yukihiro Kaneko 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic tolerance
  • biofilm
  • chronic infection
  • Pseudomonas aeruginosa
  • antibiotics

Published Papers (3 papers)

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Research

12 pages, 3560 KiB  
Article
Characteristics of Antibiotic Resistance and Tolerance of Environmentally Endemic Pseudomonas aeruginosa
by Seryoung Kim, Satomi Masai, Keiji Murakami, Momoyo Azuma, Keiko Kataoka, Mayu Sebe, Kazuya Shimizu, Tomoaki Itayama, Niwooti Whangchai, Kanda Whangchai, Ikko Ihara and Hideaki Maseda
Antibiotics 2022, 11(8), 1120; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081120 - 18 Aug 2022
Cited by 2 | Viewed by 1583
Abstract
Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of [...] Read more.
Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of 41 °C culture and specific primers was established to evaluate P. aeruginosa in the environment. The 50 strains were randomly selected among 110 isolated from the river. The results of antibiotic susceptibility evaluation showed that only 4% of environmental strains were classified as antibiotic-resistant, while 35.7% of clinical strains isolated in the same area were antibiotic-resistant, indicating a clear difference between environmental and clinical strains. However, the percentage of antibiotic-tolerance, an indicator of potential resistance risk for strains that have not become resistant, was 78.8% for clinical strains and 90% for environmental strains, suggesting that P. aeruginosa, a known cause of nosocomial infections, has a high rate of antibiotic-tolerance even in environmentally derived strains. It suggested that the rate of antibiotic-tolerance is not elicited by the presence or absence of antimicrobial exposure. The combination of established isolation and risk analysis methods presented in this study should provide accurate and efficient information on the risk level of P. aeruginosa in various regions and samples. Full article
(This article belongs to the Special Issue Antibiotic Tolerance in Pseudomonas aeruginosa)
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11 pages, 928 KiB  
Article
pruR and PA0065 Genes Are Responsible for Decreasing Antibiotic Tolerance by Autoinducer Analog-1 (AIA-1) in Pseudomonas aeruginosa
by Muhammad Reza Pahlevi, Keiji Murakami, Yuka Hiroshima, Akikazu Murakami and Hideki Fujii
Antibiotics 2022, 11(6), 773; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11060773 - 06 Jun 2022
Viewed by 1909
Abstract
Pseudomonas aeruginosa infection is considered a high-risk nosocomial infection and is very difficult to eradicate because of its tolerance to antibiotic treatment. A new compound, autoinducer analog-1 (AIA-1), has been demonstrated to reduce antibiotic tolerance, but its mechanisms remain unknown. This study aimed [...] Read more.
Pseudomonas aeruginosa infection is considered a high-risk nosocomial infection and is very difficult to eradicate because of its tolerance to antibiotic treatment. A new compound, autoinducer analog-1 (AIA-1), has been demonstrated to reduce antibiotic tolerance, but its mechanisms remain unknown. This study aimed to investigate the mechanisms of AIA-1 in the antibiotic tolerance of P. aeruginosa. A transposon mutant library was constructed using miniTn5pro, and screening was performed to isolate high tolerant mutants upon exposure to biapenem and AIA-1. We constructed a deletion mutant and complementation strain of the genes detected in transposon insertion site determination, pruR and PA0066-65-64, and performed killing assays with antibiotics and AIA-1. Gene expression upon exposure to biapenem and AIA-1 and their relationship to stress response genes were analyzed. High antibiotic tolerance was observed in Tn5-pruR and Tn5-PA0065 transposon mutants and their deletion mutants, ΔpruR and ΔPA0066-65-64. Complemented strains of pruR and PA0066-65-64 with their respective deletion mutants exhibited suppressed antibiotic tolerance. It was determined that deletion of PA0066-65-64 increased rpoS expression, and PA0066-65-64 affects antibiotic tolerance via the rpoS pathway. Additionally, antibiotics and AIA-1 were found to inhibit pruR and PA0066-65-64. This study proposed that pruR and PA0066-65-64 are members of the antibiotic tolerance suppressors. Full article
(This article belongs to the Special Issue Antibiotic Tolerance in Pseudomonas aeruginosa)
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10 pages, 13323 KiB  
Article
Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic Tolerance Reduction
by Mizuki Abe, Keiji Murakami, Yuka Hiroshima, Takashi Amoh, Mayu Sebe, Keiko Kataoka and Hideki Fujii
Antibiotics 2022, 11(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11010010 - 22 Dec 2021
Cited by 4 | Viewed by 2496
Abstract
Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects [...] Read more.
Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized P. aeruginosa quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against P. aeruginosa PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic P. aeruginosa biofilm infections. Full article
(This article belongs to the Special Issue Antibiotic Tolerance in Pseudomonas aeruginosa)
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