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Antibiotics
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Interference of Bacterial Signaling as a New Strategy for Treatment...
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Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 20672

Special Issue Editor

Dr. Hidetada Hirakawa

E-Mail Website
Guest Editor
Department of Bacteriology, Gunma University Graduate School of Medicine, Maebashi, Japan
Interests: antimicrobial resistance (AMR); biofilm; environmental response; molecular genetics; bacterial pathogenicity; infection control
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The increase and spread of AMR (antimicrobial resistance) pathogens with a shortage of new antimicrobial agents are critical issues. Therefore, new approaches are needed for the treatment of infections caused by these pathogens. Bacteria use particular signal molecules when they encounter environmental changes or contact with other bacterial members, then alter their gene expression. This manner termed “bacterial signaling” has been observed in many species including animal and plant pathogens. There is increasing evidence that it is closely associated with bacterial virulence, and characterized as virulence determinants to establish infections. Thus, bacterial signaling is proposed as a potential target for the development of antimicrobial agents. In the past two decades, many attempts to interfere with bacterial signaling are have been conducted with great interest. This Special Issue will provide updates on topics related to bacterial signaling interference and conquering refractory AMR infections. We invite manuscripts on studies that include the following topics:

  • Chemical compounds, proteins, or nucleic acids targetting bacterial signaling and their molecular mechanisms
  • Innovative chemotherapy applications and the use of inhibitors of bacterial signaling (such as combination chemotherapy)

Dr. Hidetada Hirakawa
Guest Editor

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

  • antimicrobial resistance
  • bacterial signal
  • quorum sensing
  • biofilm
  • virulence
  • combination chemotherapy

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Published Papers (5 papers)

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Research

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10 pages, 2286 KiB  
Article
Adsorption of Phenazines Produced by Pseudomonas aeruginosa Using AST-120 Decreases Pyocyanin-Associated Cytotoxicity
by Hidetada Hirakawa, Ayako Takita, Motoyuki Uchida, Yuka Kaneko, Yuto Kakishima, Koichi Tanimoto, Wataru Kamitani and Haruyoshi Tomita
Antibiotics 2021, 10(4), 434; https://doi.org/10.3390/antibiotics10040434 - 13 Apr 2021
Cited by 11 | Viewed by 2854
Abstract
AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we [...] Read more.
AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection. Full article
(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)
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15 pages, 2389 KiB  
Article
Clinical Significance of Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory Tract
by Momoyo Azuma, Keiji Murakami, Rina Murata, Keiko Kataoka, Hideki Fujii, Yoichiro Miyake and Yasuhiko Nishioka
Antibiotics 2020, 9(9), 626; https://doi.org/10.3390/antibiotics9090626 - 21 Sep 2020
Cited by 5 | Viewed by 2704
Abstract
We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the [...] Read more.
We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections. Full article
(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)
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10 pages, 1609 KiB  
Article
Identification and Characterization of Quorum-Quenching Activity of N-Acylhomoserine Lactonase from Coagulase-Negative Staphylococci
by Tomohiro Morohoshi, Yaoki Kamimura and Nobutaka Someya
Antibiotics 2020, 9(8), 483; https://doi.org/10.3390/antibiotics9080483 - 5 Aug 2020
Cited by 5 | Viewed by 3241
Abstract
N-Acylhomoserine lactones (AHLs) are used as quorum-sensing signals in Gram-negative bacteria. Many genes encoding AHL-degrading enzymes have been cloned and characterized in various microorganisms. Coagulase-negative staphylococci (CNS) are present on the skin of animals and are considered low-virulent species. The AHL-lactonase gene [...] Read more.
N-Acylhomoserine lactones (AHLs) are used as quorum-sensing signals in Gram-negative bacteria. Many genes encoding AHL-degrading enzymes have been cloned and characterized in various microorganisms. Coagulase-negative staphylococci (CNS) are present on the skin of animals and are considered low-virulent species. The AHL-lactonase gene homologue, ahlS, was present in the genomes of the CNS strains Staphylococcus carnosus, Staphylococcus haemolyticus, Staphylococcus saprophyticus, and Staphylococcus sciuri. We cloned the candidate ahlS homologue from six CNS strains into the pBBR1MCS5 vector. AhlS from the CNS strains showed a higher degrading activity against AHLs with short acyl chains compared to those with long acyl chains. AhlS from S. sciuri was expressed and purified as a maltose-binding protein (MBP) fusion. Pseudomonas aeruginosa is an opportunistic pathogen that regulates several virulence factors such as elastase and pyocyanin by quorum-sensing systems. When MBP-AhlS was added to the culture of P. aeruginosa PAO1, pyocyanin production and elastase activity were substantially reduced compared to those in untreated PAO1. These results demonstrate that the AHL-degrading activity of AhlS from the CNS strains can inhibit quorum sensing in P. aeruginosa PAO1. Full article
(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)
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Review

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18 pages, 725 KiB  
Review
The Roles of Microbial Cell-Cell Chemical Communication Systems in the Modulation of Antimicrobial Resistance
by Ying Huang, Yufan Chen and Lian-hui Zhang
Antibiotics 2020, 9(11), 779; https://doi.org/10.3390/antibiotics9110779 - 6 Nov 2020
Cited by 14 | Viewed by 3762
Abstract
Rapid emergence of antimicrobial resistance (AMR) has become a critical challenge worldwide. It is of great importance to understand how AMR is modulated genetically in order to explore new antimicrobial strategies. Recent studies have unveiled that microbial communication systems, which are known to [...] Read more.
Rapid emergence of antimicrobial resistance (AMR) has become a critical challenge worldwide. It is of great importance to understand how AMR is modulated genetically in order to explore new antimicrobial strategies. Recent studies have unveiled that microbial communication systems, which are known to play key roles in regulation of bacterial virulence, are also associated with the formation and regulation of AMR. These microbial cell-to-cell chemical communication systems, including quorum sensing (QS) and pathogen–host communication mechanisms, rely on detection and response of various chemical signal molecules, which are generated either by the microbe itself or host cells, to activate the expression of virulence and AMR genes. This article summarizes the generic signaling mechanisms of representative QS and pathogen–host communications systems, reviews the current knowledge regarding the roles of these chemical communication systems in regulation of AMR, and describes the strategies developed over the years for blocking bacterial chemical communication systems in disease control. The research progress in this field suggests that the bacterial cell-cell communication systems are a promising target not only for disease control but also for curbing the problem of microbial drug resistance. Full article
(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)
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15 pages, 693 KiB  
Review
Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy
by Hidetada Hirakawa, Jun Kurushima, Yusuke Hashimoto and Haruyoshi Tomita
Antibiotics 2020, 9(10), 635; https://doi.org/10.3390/antibiotics9100635 - 23 Sep 2020
Cited by 59 | Viewed by 7388
Abstract
Bacteria adapt to changes in their environment using a mechanism known as the two-component regulatory system (TCS) (also called “two-component signal transduction system” or “two-component system”). It comprises a pair of at least two proteins, namely the sensor kinase and the response regulator. [...] Read more.
Bacteria adapt to changes in their environment using a mechanism known as the two-component regulatory system (TCS) (also called “two-component signal transduction system” or “two-component system”). It comprises a pair of at least two proteins, namely the sensor kinase and the response regulator. The former senses external stimuli while the latter alters the expression profile of bacterial genes for survival and adaptation. Although the first TCS was discovered and characterized in a non-pathogenic laboratory strain of Escherichia coli, it has been recognized that all bacteria, including pathogens, use this mechanism. Some TCSs are essential for cell growth and fitness, while others are associated with the induction of virulence and drug resistance/tolerance. Therefore, the TCS is proposed as a potential target for antimicrobial chemotherapy. This concept is based on the inhibition of bacterial growth with the substances acting like conventional antibiotics in some cases. Alternatively, TCS targeting may reduce the burden of bacterial virulence and drug resistance/tolerance, without causing cell death. Therefore, this approach may aid in the development of antimicrobial therapeutic strategies for refractory infections caused by multi-drug resistant (MDR) pathogens. Herein, we review the progress of TCS inhibitors based on natural and synthetic compounds. Full article
(This article belongs to the Special Issue Interference of Bacterial Signaling as a New Strategy for Treatment of AMR Pathogens)
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