Bacteriophages and Other Alternative Antimicrobials to Combat Multidrug Resistance

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Bacteriophages".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 8656

Special Issue Editors


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Guest Editor
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Interests: bacteriophage biology and bacteriophage therapy

E-Mail
Guest Editor
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Interests: bacteriophage molecular biology and bacteriophage therapy

Special Issue Information

Dear Colleagues,

The global spread of antibiotic resistance in pathogenic bacteria has become an accelerating public health disaster that calls for the development of novel therapeutic approaches. These new antibacterial agents include bacteriophages, small molecule antibiotics, monoclonal antibodies, antivirulence drugs, antimicrobial peptides, bacteriocins, and predatory bacteria. Some of these novel drugs have shown significant efficacy in laboratory animals and in humans. There are publications that describe multiple positive outcomes in patients with different severe multidrug-resistant infections by compassionate use as well as some successful clinical trials for evaluating new antibacterials. However, much work remains!

This Special Issue is focused on isolation, synthesis, engineering, characterization, preclinical testing and clinical use of any novel antibacterials that are alternatives to classical antibiotics. Articles covering comparisons and combinations of new drugs and standard-of-care antibiotics are also welcome. Additional topics of interest will include safety, stability and immunogenicity of novel drugs, improved formulations, manufacturing, storage, delivery, regulatory aspects, and the development of bacterial resistance and ways to overcome it. Both original papers and review articles will be considered for publication in this Special Issue of Antibiotics.

Dr. Andrey A. Filippov
Dr. Mikeljon P. Nikolich
Guest Editors

Manuscript Submission Information

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Keywords

  • multidrug resistance
  • alternative antibacterials
  • bacteriophage therapy
  • phage-antibiotic synergy
  • phage lysins
  • small molecule drugs
  • monoclonal antibodies
  • antivirulence drugs
  • pharmacokinetics and pharmacodynamics
  • resistance to novel drugs

Published Papers (4 papers)

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Research

28 pages, 8278 KiB  
Article
Use of the Naturally Occurring Bacteriophage Grouping Model for the Design of Potent Therapeutic Cocktails
by Tea Glonti, Michael Goossens, Christel Cochez, Sabrina Green, Sayali Gorivale, Jeroen Wagemans, Rob Lavigne and Jean-Paul Pirnay
Antibiotics 2024, 13(5), 385; https://doi.org/10.3390/antibiotics13050385 - 24 Apr 2024
Viewed by 1297
Abstract
The specificity of phages and their ability to evolve and overcome bacterial resistance make them potentially useful as adjuncts in the treatment of antibiotic-resistant bacterial infections. The goal of this study was to mimic a natural grouping of phages of interest and to [...] Read more.
The specificity of phages and their ability to evolve and overcome bacterial resistance make them potentially useful as adjuncts in the treatment of antibiotic-resistant bacterial infections. The goal of this study was to mimic a natural grouping of phages of interest and to evaluate the nature of their proliferation dynamics with bacteria. We have, for the first time, transferred naturally occurring phage groups directly from their sources of isolation to in vitro and identified 13 P. aeruginosa and 11 K. pneumoniae phages of 18 different genera, whose host range was grouped as 1.2–17%, 28–48% and 60–87%, using a large collection of P. aeruginosa (n = 102) and K. pneumoniae (n = 155) strains carrying different virulence factors and phage binding receptors. We introduced the interpretation model curve for phage liquid culturing, which allows easy and quick analysis of bacterial and phage co-proliferation and growth of phage-resistant mutants (PRM) based on qualitative and partially quantitative evaluations. We assayed phage lytic activities both individually and in 14 different cocktails on planktonic bacterial cultures, including three resistotypes of P. aeruginosa (PAO1, PA14 and PA7) and seven K. pneumoniae strains of different capsular serotypes. Based on the results, the natural phage cocktails designed and tested in this study largely performed well and inhibited PRM growth either synergistically or in proto-cooperation. This study contributes to the knowledge of phage behavior in cocktails and the formulation of therapeutic phage preparations. The paper also provides a detailed description of the methods of working with phages. Full article
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24 pages, 2381 KiB  
Article
Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa
by Addisu D. Teklemariam, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Ishtiaq Qadri, Turki Alamri, Ahmed Esmael and Steve Harakeh
Antibiotics 2023, 12(3), 497; https://doi.org/10.3390/antibiotics12030497 - 2 Mar 2023
Cited by 3 | Viewed by 2842
Abstract
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a serious public health threat in multiple clinical settings. In this study, we detail the isolation of a lytic bacteriophage, vB_PseuP-SA22, from wastewater using a clinical strain of CRPA. Transmission electron microscopy (TEM) analysis identified that the phage [...] Read more.
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a serious public health threat in multiple clinical settings. In this study, we detail the isolation of a lytic bacteriophage, vB_PseuP-SA22, from wastewater using a clinical strain of CRPA. Transmission electron microscopy (TEM) analysis identified that the phage had a podovirus morphology, which agreed with the results of whole genome sequencing. BLASTn search allowed us to classify vB_PseuP-SA22 into the genus Bruynoghevirus. The genome of vB_PseuP-SA22 consisted of 45,458 bp of double-stranded DNA, with a GC content of 52.5%. Of all the open reading frames (ORFs), only 26 (44.8%) were predicted to encode certain functional proteins, whereas the remaining 32 (55.2%) ORFs were annotated as sequences coding functionally uncharacterized hypothetical proteins. The genome lacked genes coding for toxins or markers of lysogenic phages, including integrases, repressors, recombinases, or excisionases. The phage produced round, halo plaques with a diameter of 1.5 ± 2.5 mm on the bacterial lawn. The TEM revealed that vB_PseuP-SA22 has an icosahedral head of 57.5 ± 4.5 nm in length and a short, non-contractile tail (19.5 ± 1.4 nm). The phage showed a latent period of 30 min, a burst size of 300 PFU/infected cells, and a broad host range. vB_PseuP-SA22 was found to be stable between 4–60 °C for 1 h, while the viability of the virus was reduced at temperatures above 60 °C. The phage showed stability at pH levels between 5 and 11. vB_PauP-SA22 reduced the number of live bacteria in P. aeruginosa biofilm by almost five logs. The overall results indicated that the isolated phage could be a candidate to control CRPA infections. However, experimental in vivo studies are essential to ensure the safety and efficacy of vB_PauP-SA22 before its use in humans. Full article
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18 pages, 2312 KiB  
Article
Design of a Bacteriophage Cocktail Active against Shigella Species and Testing of Its Therapeutic Potential in Galleria mellonella
by Andrey A. Filippov, Wanwen Su, Kirill V. Sergueev, Richard T. Kevorkian, Erik C. Snesrud, Apichai Srijan, Yunxiu He, Derrick E. Fouts, Woradee Lurchachaiwong, Patrick T. McGann, Damon W. Ellison, Brett E. Swierczewski and Mikeljon P. Nikolich
Antibiotics 2022, 11(11), 1659; https://doi.org/10.3390/antibiotics11111659 - 19 Nov 2022
Cited by 1 | Viewed by 2103
Abstract
Shigellosis is a leading global cause of diarrheal disease and travelers’ diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. [...] Read more.
Shigellosis is a leading global cause of diarrheal disease and travelers’ diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. The genomes of 32 phages were sequenced, and based on genomic comparisons belong to seven taxonomic genera: Teetrevirus, Teseptimavirus, Kayfunavirus, Tequatrovirus, Mooglevirus, Mosigvirus and Hanrivervirus. Phage host ranges were determined with a diverse panel of 95 clinical isolates of Shigella from Southeast Asia and other geographic regions, representing different species and serotypes. Three-phage mixtures were designed, with one possessing lytic activity against 89% of the strain panel. This cocktail exhibited lytic activity against 100% of S. sonnei isolates, 97.2% of S. flexneri (multiple serotypes) and 100% of S. dysenteriae serotypes 1 and 2. Another 3-phage cocktail composed of two myophages and one podophage showed both a broad host range and the ability to completely sterilize liquid culture of a model virulent strain S. flexneri 2457T. In a Galleria mellonella model of lethal infection with S. flexneri 2457T, this 3-phage cocktail provided a significant increase in survival. Full article
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9 pages, 1131 KiB  
Communication
Combination Treatment for Inhibition of the Growth of Staphylococcus aureus with Recombinant SAP8 Endolysin and Nisin
by Seon-Gyu Kim, Shehzad Abid Khan, Young-Duck Lee, Jong-Hyun Park and Gi-Seong Moon
Antibiotics 2022, 11(9), 1185; https://doi.org/10.3390/antibiotics11091185 - 2 Sep 2022
Cited by 3 | Viewed by 1680
Abstract
Staphylococcus aureus, a pathogenic species of genus Staphylococcus involved in foodborne illness always remain among the top priorities of the world major concerns. In the present study, we have used recombinant SAP8 endolysin from the bacteriophage SAP8 and commercial nisin to inhibit [...] Read more.
Staphylococcus aureus, a pathogenic species of genus Staphylococcus involved in foodborne illness always remain among the top priorities of the world major concerns. In the present study, we have used recombinant SAP8 endolysin from the bacteriophage SAP8 and commercial nisin to inhibit the viability of pathogenic S. aureus KCTC 3881 cells; however, the approach was not identified as cost-effective. A gradual decrease in the viable S. aureus KCTC 3881 cell counts was observed with an increase in the concentrations of recombinant SAP8 endolysin and nisin. However, combined treatment with recombinant SAP8 endolysin and nisin decreased the viable S. aureus KCTC 3881 cell counts in a significant manner. The combination of 0.01 µM of recombinant SAP8 endolysin with 9 IU/mL and 18 IU/mL of nisin demonstrated a promising decrease in the viable cell counts of the strain. Under the scanning electron microscope, the combination treatment with 0.01 µM of recombinant SAP8 endolysin and 18 IU/mL of nisin showed complete cellular destruction of S. aureus KCTC 3881. We propose that a combination of recombinant SAP8 endolysin and nisin could be a strong alternative to antibiotics to control the growth of S. aureus including MRSA. Full article
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