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Antibiotics
Special Issues
Dissecting Antimicrobial Resistance with Systems Approach
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Dissecting Antimicrobial Resistance with Systems Approach

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

Deadline for manuscript submissions: closed (1 June 2022) | Viewed by 3783

Special Issue Editor

Dr. Yan Zhu

E-Mail Website
Guest Editor
Biomedicine Discovery Institute, Monash University, Melbourne, Australia
Interests: antimicrobial resistance; polymyxin; genome-scale metabolic model; systems pharmacology

Special Issue Information

Dear colleagues,

Antimicrobial resistance poses a critical challenge to human health globally. With a marked decline in discovery of novel antimicrobials, the world is now facing an enormous and growing threat from the emergence of bacteria that are resistant to almost all current antibiotics. In 2017, WHO urged the development of novel antimicrobial treatments against the deadly superbugs, namely Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. Systems pharmacology and genome-scale metabolic modelling have been increasingly employed to decipher the complex interplay of multiple biological pathways associated with antimicrobial resistance. Understanding such mechanisms is critical for the development of novel antimicrobial therapies to combat the resistance.

This special issue aims to provide a forum to disseminate the latest results on systems antimicrobial pharmacology. Papers on the following aspects are of particular interest: discovering novel antimicrobial resistance elements with large-scale genomic or proteomic analysis, elucidating the mechanisms of antimicrobial resistance using multi-omics approach, molecular dynamics simulation, and/or genome-scale metabolic modelling.

Dr. Yan Zhu
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

  • Superbugs
  • Antimicrobial resistance
  • Genomics
  • Proteomics
  • Transcriptomics
  • Metabolomics
  • Lipidomics
  • Molecular dynamics simulation
  • Genome-scale metabolic modelling
  • Systems pharmacology

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Published Papers (1 paper)

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Research

18 pages, 2377 KiB  
Article
Clinically Relevant Concentrations of Polymyxin B and Meropenem Synergistically Kill Multidrug-Resistant Pseudomonas aeruginosa and Minimize Biofilm Formation
by Hasini Wickremasinghe, Heidi H. Yu, Mohammad A. K. Azad, Jinxin Zhao, Phillip J. Bergen, Tony Velkov, Qi Tony Zhou, Yan Zhu and Jian Li
Antibiotics 2021, 10(4), 405; https://doi.org/10.3390/antibiotics10040405 - 8 Apr 2021
Cited by 13 | Viewed by 3199
Abstract
The emergence of antibiotic resistance has severely impaired the treatment of chronic respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Since the reintroduction of polymyxins as a last-line therapy against MDR Gram-negative bacteria, resistance to its monotherapy and recurrent infections continue to [...] Read more.
The emergence of antibiotic resistance has severely impaired the treatment of chronic respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Since the reintroduction of polymyxins as a last-line therapy against MDR Gram-negative bacteria, resistance to its monotherapy and recurrent infections continue to be reported and synergistic antibiotic combinations have been investigated. In this study, comprehensive in vitro microbiological evaluations including synergy panel screening, population analysis profiling, time-kill kinetics, anti-biofilm formation and membrane damage analysis studies were conducted to evaluate the combination of polymyxin B and meropenem against biofilm-producing, polymyxin-resistant MDR P. aeruginosa. Two phylogenetically unrelated MDR P. aeruginosa strains, FADDI-PA060 (MIC of polymyxin B [MICpolymyxin B], 64 mg/L; MICmeropenem, 64 mg/L) and FADDI-PA107 (MICpolymyxin B, 32 mg/L; MICmeropenem, 4 mg/L) were investigated. Genome sequencing identified 57 (FADDI-PA060) and 50 (FADDI-PA107) genes predicted to confer resistance to a variety of antimicrobials, as well as multiple virulence factors in each strain. The presence of resistance genes to a particular antibiotic class generally aligned with MIC results. For both strains, all monotherapies of polymyxin B failed with substantial regrowth and biofilm formation. The combination of polymyxin B (16 mg/L)/meropenem (16 mg/L) was most effective, enhancing initial bacterial killing of FADDI-PA060 by ~3 log10 CFU/mL, followed by a prolonged inhibition of regrowth for up to 24 h with a significant reduction in biofilm formation (* p < 0.05). Membrane integrity studies revealed a substantial increase in membrane depolarization and membrane permeability in the surviving cells. Against FADDI-PA107, planktonic and biofilm bacteria were completely eradicated. In summary, the combination of polymyxin B and meropenem demonstrated synergistic bacterial killing while reinstating the efficacy of two previously ineffective antibiotics against difficult-to-treat polymyxin-resistant MDR P. aeruginosa. Full article
(This article belongs to the Special Issue Dissecting Antimicrobial Resistance with Systems Approach)
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