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Antibiotics
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Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach
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Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach

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

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 14588

Special Issue Editors

Prof. Dr. Christian Hulen

E-Mail Website
Guest Editor
Laboratory of Microbiology — Bacterial Communication and Anti-Infectious Strategies, University of Rouen Normandy, 27000 Evreux, France
Interests: antibiotic
Prof. Dr. Olivier Lesouhaitier

E-Mail Website
Guest Editor
Laboratory of Microbiology—Bacterial Communication and Anti-infectious Strategies, University of Rouen Normandy, 27000 Evreux, France
Interests: cell biology; microbiology; communication and signal processing; PCR; bacteriology; antibiotic resistance; antimicrobials; microbial molecular biology; molecular microbiology; applied microbiology

Special Issue Information

Dear Colleagues,

Pseudomonas aeruginosa regarding its antibiotic resistance is one of the six ESKAPE pathogens with the highest risk of mortality, particularly in developing countries belongs. The World Health Organization as classified this pathogen as priority 1 (critical) for its resistance to carbapenem needing to urgently find new to counteract P.aeruginosa. The presence in numerous human environments of MDR P. aeruginosa poses a major health problem for the treatment of sporadic or chronic infections and for the appearance of persisters bacteria. In this special issue we would like to first review recent data on the mechanisms of resistance of P. aeruginosa to antibiotics and growth inhibitors. The presentation of new fields of research for the development of new therapeutic strategies to fight against multiresistance, proliferation and persistence of P. aeruginosa should be the subject of a second part. In addition, innovative manuscripts whose subject approaches the themes of this special issue may be analyzed.

Resistance of P. aeruginosa to antibiotics and new therapeutic strategies.

  1. What's new in the Mex system?
  2. Role of secondary systems in antibiotic resistance: MFS, SMR, MATE, ABC.
  3. Changes in membrane permeation in antibiotic resistance: porins, LPS, permeases.
  4. New plasmids and antibiotic degrading enzymes.
  5. The new anti-virulence compounds.
  6. Quorum-quenching molecules in the treatment of infections.
  7. Design and use of new antimicrobial peptides.
  8. Compounds targeting bacterial cell envelope.
  9. The use of adjuvant compounds.
  10. The effects of anti-biofilm molecules.
  11. Latest results on bacteriotherapy.
  12. The use of specific phages in the fight against MDR P.aeruginosa.

Prof. Dr. Christian Hulen
Prof. Dr. Olivier Lesouhaitier
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.

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Published Papers (5 papers)

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Research

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17 pages, 3055 KiB  
Article
Evaluating the In Vivo Virulence of Environmental Pseudomonas aeruginosa Using Microinjection Model of Zebrafish (Danio rerio)
by Edit Kaszab, Dongze Jiang, István Szabó, Balázs Kriszt, Béla Urbányi, Sándor Szoboszlay, Rózsa Sebők, Illés Bock and Zsolt Csenki-Bakos
Antibiotics 2023, 12(12), 1740; https://doi.org/10.3390/antibiotics12121740 - 15 Dec 2023
Cited by 1 | Viewed by 1920
Abstract
(1) Background: Microinjection of zebrafish (Danio rerio) embryos offers a promising model for studying the virulence and potential environmental risks associated with Pseudomonas aeruginosa. (2) Methods: This work aimed to develop a P. aeruginosa infection model using two parallel exposition [...] Read more.
(1) Background: Microinjection of zebrafish (Danio rerio) embryos offers a promising model for studying the virulence and potential environmental risks associated with Pseudomonas aeruginosa. (2) Methods: This work aimed to develop a P. aeruginosa infection model using two parallel exposition pathways on zebrafish larvae with microinjection into the yolk and the perivitelline space to simultaneously detect the invasive and cytotoxic features of the examined strains. The microinjection infection model was validated with 15 environmental and clinical strains of P. aeruginosa of various origins, antibiotic resistance profiles, genotypes and phenotypes: both exposition pathways were optimized with a series of bacterial dilutions, different drop sizes (injection volumes) and incubation periods. Besides mortality, sublethal symptoms of the treated embryos were detected and analyzed. (3) Results: According to the statistical evaluation of our results, the optimal parameters (dilution, drop size and incubation period) were determined. (4) Conclusions: The tested zebrafish embryo microinjection infection model is now ready for use to determine the in vivo virulence and ecological risk of environmental P. aeruginosa. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)
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20 pages, 5308 KiB  
Article
The GDP-Mannose Dehydrogenase of Pseudomonas aeruginosa: An Old and New Target to Fight against Antibiotics Resistance of Mucoid Strains
by Christian Hulen
Antibiotics 2023, 12(12), 1649; https://doi.org/10.3390/antibiotics12121649 - 22 Nov 2023
Viewed by 1413
Abstract
Alginates play an important role in the resistance of mucoid strains of Pseudomonas aeruginosa to antibiotics, as well as their persistence by escaping the immune defense system. GDP-mannose dehydrogenase (GMD) is the key enzyme in alginate biosynthesis by catalyzing the irreversible double oxidation [...] Read more.
Alginates play an important role in the resistance of mucoid strains of Pseudomonas aeruginosa to antibiotics, as well as their persistence by escaping the immune defense system. GDP-mannose dehydrogenase (GMD) is the key enzyme in alginate biosynthesis by catalyzing the irreversible double oxidation of GDP-mannose to GDP-mannuronate. GDP-mannose dehydrogenase purified from mucoid strains exhibits strong negative cooperativity for its substrate, the GDP-mannose, with a KM of 13 µM for the site of strong affinity and 3 mM for this weak of a binding. The presence of a nucleotide strongly associated with the enzyme was detected, confirming the fact that the substrate oxidation reaction takes place in two distinct steps, with the substrate blocked on the enzyme in a half-oxidation state in the form of a hemiacetal. As the GMD polypeptide has only one site for substrate binding, our results tend to confirm the fact that the enzyme functions in a dimer form. The GDP-mannose dehydrogenase inhibition strategy that we developed a few years ago, based on the synthesis of substrate analogs, has shown its effectiveness. The addition of an alkynyl radical on carbon 6 of the mannose grafted to an amino-sulfonyl-guanosine allows, at a concentration of 0.5 mM, to inhibit GMD by 90%. As we had previously shown the effectiveness of these analogs on the sensitivity of mucoid strains of Pseudomonas aeruginosa to aminoglycosides, this revives the interest in the synthesis of new inhibitors of GDP-mannose dehydrogenase. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)
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11 pages, 753 KiB  
Article
Antibiogram Profile and Detection of Resistance Genes in Pseudomonas aeruginosa Recovered from Hospital Wastewater Effluent
by Joan U. Okafor and Uchechukwu U. Nwodo
Antibiotics 2023, 12(10), 1517; https://doi.org/10.3390/antibiotics12101517 - 6 Oct 2023
Cited by 2 | Viewed by 2359
Abstract
The nosocomial pathogen Pseudomonas aeruginosa (P. aeruginosa) is characterized by increased prevalence in hospital wastewater and is a public health concern. Untreated wastewater severely challenges human health when discharged into nearby aquatic ecosystems. The antibiogram profiles and resistance genes of P. [...] Read more.
The nosocomial pathogen Pseudomonas aeruginosa (P. aeruginosa) is characterized by increased prevalence in hospital wastewater and is a public health concern. Untreated wastewater severely challenges human health when discharged into nearby aquatic ecosystems. The antibiogram profiles and resistance genes of P. aeruginosa were evaluated in this study. Wastewater effluents were obtained from a hospital within a six-month sampling period. After the samples were processed and analysed, P. aeruginosa was identified by polymerase chain reaction (PCR) by amplifying OprI and OprL genes. The Kirby–Bauer diffusion technique was employed to check the susceptibility profiles of P. aeruginosa which were further interpreted using CLSI guidelines. A total of 21 resistance genes were investigated among the isolates. The sum of 81 positive P. aeruginosa were isolated in this study. This study’s mean count of Pseudomonas aeruginosa ranged from 2.4 × 105 to 6.5 × 105 CFU/mL. A significant proportion of the isolates were susceptible to imipenem (93%), tobramycin (85%), norfloxacin (85%), aztreonam (70%), ciprofloxacin (51%), meropenem (47%), levofloxacin (43%), and gentamicin (40%). Meanwhile, a low susceptibility was recorded for amikacin and ceftazidime. The overall multiple antibiotics resistance index (MARI) ranged from 0.3 to 0.9, with 75% of the multidrug-resistant isolates. The assessment of β-lactam-resistant genes revealed blaOXA-1 (3.7%) and blaSHV (2.4%). The frequency of carbapenem genes was 6.6% for blaIMP, 6.6% for blaKPC, 6.6% for blaoxa-48, 2.2% for blaNDM-1, 2.2% for blaGES, and 2.2% for blaVIM. Of the aminoglycoside genes screened, 8.6% harboured strA, 11.5% harboured aadA, and 1.5% harboured aph(3)-Ia(aphA1). Only one non-β-lactamase gene (qnrA) was detected, with a prevalence of 4.9%. The findings of this study revealed a high prevalence of multidrug-resistant P. aeruginosa and resistance determinants potentially posing environmental health risks. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)
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Review

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16 pages, 3134 KiB  
Review
Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa
by Changhong Yin, Md Zahidul Alam, John T. Fallon and Weihua Huang
Antibiotics 2024, 13(2), 119; https://doi.org/10.3390/antibiotics13020119 - 25 Jan 2024
Cited by 3 | Viewed by 5787
Abstract
Pseudomonas aeruginosa (P. aeruginosa) with multi-drug resistance (MDR) is a major cause of serious healthcare-associated infections, leading to high morbidity and mortality. This opportunistic pathogen is responsible for various infectious diseases, such as those seen in cystic fibrosis, ventilator-associated pneumonia, urinary [...] Read more.
Pseudomonas aeruginosa (P. aeruginosa) with multi-drug resistance (MDR) is a major cause of serious healthcare-associated infections, leading to high morbidity and mortality. This opportunistic pathogen is responsible for various infectious diseases, such as those seen in cystic fibrosis, ventilator-associated pneumonia, urinary tract infection, otitis externa, and burn and wound injuries. Due to its relatively large genome, P. aeruginosa has great diversity and can use various molecular mechanisms for antimicrobial resistance. For example, outer membrane permeability can contribute to antimicrobial resistance and is determined by lipopolysaccharide (LPS) and porin proteins. Recent findings on the regulatory interaction between peptidoglycan and LPS synthesis provide additional clues against pathogenic P. aeruginosa. This review focuses on recent advances in antimicrobial agents and inhibitors targeting LPS and porin proteins. In addition, we explore current and emerging treatment strategies for MDR P. aeruginosa, including phages, vaccines, nanoparticles, and their combinatorial therapies. Novel strategies and their corresponding therapeutic agents are urgently needed for combating MDR pathogens. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)
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Other

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6 pages, 236 KiB  
Case Report
Insights into the Evolution of P. aeruginosa Antimicrobial Resistance in a Patient Undergoing Intensive Therapy
by Kwee Chin Liew, Jessica O’Keeffe, Heera Rajandas, Yin Peng Lee, Owen Harris, Sivachandran Parimannan, Larry Croft and Eugene Athan
Antibiotics 2023, 12(3), 483; https://doi.org/10.3390/antibiotics12030483 - 28 Feb 2023
Cited by 2 | Viewed by 2067
Abstract
Whole genome sequencing (WGS) provides insights into the evolution of antimicrobial resistance, an urgent global health threat. Using WGS, we observe evolutionary adaptation of a Pseudomonas aeruginosa strain within an immunocompromised patient undergoing antibiotic therapy. Two blood isolates (EA-86 and EA-87) from the [...] Read more.
Whole genome sequencing (WGS) provides insights into the evolution of antimicrobial resistance, an urgent global health threat. Using WGS, we observe evolutionary adaptation of a Pseudomonas aeruginosa strain within an immunocompromised patient undergoing antibiotic therapy. Two blood isolates (EA-86 and EA-87) from the patient evolved separate adaptations for antibiotic resistance, while sharing common adaptive mutations for host immune evasion. In EA-86, a silencing mutation in the antibiotic efflux pump repressor, NfxB, increased antibiotic resistance, while in EA-87, a similar mutation was seen in the antibiotic efflux pump repressor mexR. The number of genomic variants between the two isolates give a divergence time estimate of the order of 1000 generations. This time is sufficient for a bacterial lineage to have evolved an SNP in every position in the genome and been fixed if advantageous. This demonstrates the evolutionary adaptive power accessible to bacteria and the timescale for a brute-force functional survey of the SNP fitness landscape. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Therapeutic Approach)
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