Special Issue "Bacteriophage Lysins in the Era of Antibiotic Resistance"

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 6498

Special Issue Editor

Prof. Dr. Hongping Wei
E-Mail Website
Guest Editor
Wuhan Institute of Virology Chinese Academy of Sciences, Wuhan, China
Interests: bacteriophage; lysin; rapid microbial detection; African swine fever virus

Special Issue Information

Dear Colleagues,

The World Health Organization has listed microbial resistance to antibiotics among the major global health threats. It is not rare to see infections caused by bacteria resistant to all of the current antibiotics, leading to increased morbidity and mortality. This global challenge is provoking a high interest in seeking alternatives to traditional antibiotics. Bacteriophage lysins are hydrolytic enzymes capable of specifically recognizing the bacterial cell wall to cleave peptidoglycan for the release of progeny virions during the lytic cycle of bacteriophage. The advantages of lysins include fast bactericidal activity and low chance for bacteria to generate resistance. The number of studies on lysins has increased significantly in recent years. Some lysins are in the phase III clinical trial stage for treating antibiotic resistant infections. The aim of this Special Issue is to provide readers with an updated overview of the field, highlighting the most recent advances in lysin research, both in preclinical and clinical settings.

We welcome contributions including, but not limited to, the following topics:

  • Discovery and engineering variants of lysins;
  • Synergistic combinations with other antimicrobials;
  • Safety and host immune response;
  • Development of lysins into pharmaceutical products;
  • Other applications of lysins, such as in agriculture and cosmetics.

Prof. Dr. Hongping Wei
Guest Editor

Manuscript Submission Information

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Keywords

  • Antibiotic resistance
  • Lysin
  • Bacteriophage
  • Enzybiotics

Published Papers (5 papers)

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Research

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Article
Novel Phage Lysin Abp013 against Acinetobacter baumannii
Antibiotics 2022, 11(2), 169; https://doi.org/10.3390/antibiotics11020169 - 28 Jan 2022
Cited by 2 | Viewed by 1546
Abstract
As antimicrobial resistance (AMR) continues to pose an ever-growing global health threat, propelling us into a post-antibiotic era, novel alternative therapeutic agents are urgently required. Lysins are bacteriophage-encoded peptidoglycan hydrolases that display great potential as a novel class of antimicrobials for therapeutics. While [...] Read more.
As antimicrobial resistance (AMR) continues to pose an ever-growing global health threat, propelling us into a post-antibiotic era, novel alternative therapeutic agents are urgently required. Lysins are bacteriophage-encoded peptidoglycan hydrolases that display great potential as a novel class of antimicrobials for therapeutics. While lysins against Gram-positive bacteria are highly effective when applied exogenously, it is challenging for lysins to access and cleave the peptidoglycan of Gram-negative bacteria due to their outer membrane. In this study, we identify a novel phage lysin Abp013 against Acinetobacter baumannii. Abp013 exhibited significant lytic activity against multidrug-resistant strains of A. baumannii. Notably, we found that Abp013 was able to tolerate the presence of human serum by up to 10%. Using confocal microscopy and LIVE/DEAD staining, we show that Abp013 can access and kill the bacterial cells residing in the biofilm. These results highlight the intrinsic bacteriolytic property of Abp013, suggesting the promising use of Abp013 as a novel therapeutic agent. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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Article
Optimization of Propidium Monoazide qPCR (Viability-qPCR) to Quantify the Killing by the Gardnerella-Specific Endolysin PM-477, Directly in Vaginal Samples from Women with Bacterial Vaginosis
Antibiotics 2022, 11(1), 111; https://doi.org/10.3390/antibiotics11010111 - 15 Jan 2022
Cited by 2 | Viewed by 577
Abstract
Quantification of the number of living cells in biofilm or after eradication treatments of biofilm, is problematic for different reasons. We assessed the performance of pre-treatment of DNA, planktonic cells and ex vivo vaginal biofilms of Gardnerella with propidium monoazide (PMAxx) to prevent [...] Read more.
Quantification of the number of living cells in biofilm or after eradication treatments of biofilm, is problematic for different reasons. We assessed the performance of pre-treatment of DNA, planktonic cells and ex vivo vaginal biofilms of Gardnerella with propidium monoazide (PMAxx) to prevent qPCR-based amplification of DNA from killed cells (viability-qPCR). Standard PMAxx treatment did not completely inactivate free DNA and did not affect living cells. While culture indicated that killing of planktonic cells by heat or by endolysin was complete, viability-qPCR assessed only log reductions of 1.73 and 0.32, respectively. Therefore, we improved the standard protocol by comparing different (combinations of) parameters, such as concentration of PMAxx, and repetition, duration and incubation conditions of treatment. The optimized PMAxx treatment condition for further experiments consisted of three cycles, each of: 15 min incubation on ice with 50 µM PMAxx, followed by 15 min-long light exposure. This protocol was validated for use in vaginal samples from women with bacterial vaginosis. Up to log2.2 reduction of Gardnerella cells after treatment with PM-477 was documented, despite the complex composition of the samples, which might have hampered the activity of PM-477 as well as the quantification of low loads by viability-qPCR. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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Article
Efficacy of the Endolysin-Based Antibacterial Gel for Treatment of Anaerobic Infection Caused by Fusobacterium necrophorum
Antibiotics 2021, 10(10), 1260; https://doi.org/10.3390/antibiotics10101260 - 16 Oct 2021
Viewed by 737
Abstract
Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. Fusobacterium necrophorum is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this [...] Read more.
Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. Fusobacterium necrophorum is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this kind of infection needs to be optimized. Here, we examined the possibility of treating F. necrophorum-induced abscess wound infections with candidate therapeutics based on three endolysins with activity against a broad spectrum of aerobe Gram-negative pathogens. Antibacterial gel containing three Gram-negative bacteria-targeting endolysins, LysAm24, LysAp22, and LysECD7, was formulated for topical use. Abscess formation was induced in rabbits with F. necrophorum and caused systemic infection. The survival and lifespan of the animals, general parameters, and biochemical and hematological blood tests were analyzed to assess the effectiveness of the gel treatment for the wound infection. The administration of the investigated gel twice per day for 5 days resulted in less acute inflammation, with decreased leukocytes and segmented neutrophils in the blood, retardation of infection progression, and an almost two-fold increase in the lifespan of the animals compared to the placebo group. The results indicate that endolysin-based therapy is an effective approach to treat anaerobic bacterial infections. The use of endolysins as independent pharmaceuticals, or their combination with antibiotics, could significantly reduce the development of complications in infectious diseases caused by sensitive bacterial species. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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Article
A Highly Active Chimeric Lysin with a Calcium-Enhanced Bactericidal Activity against Staphylococcus aureus In Vitro and In Vivo
Antibiotics 2021, 10(4), 461; https://doi.org/10.3390/antibiotics10040461 - 19 Apr 2021
Cited by 4 | Viewed by 937
Abstract
Lysins, including chimeric lysins, have recently been explored as novel promising alternatives to failing antibiotics in treating multi-drug resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Herein, by fusing the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the Ply187 lysin with the non-SH3b [...] Read more.
Lysins, including chimeric lysins, have recently been explored as novel promising alternatives to failing antibiotics in treating multi-drug resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Herein, by fusing the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the Ply187 lysin with the non-SH3b cell-wall binding domain from the LysSA97 lysin, a new chimeric lysin ClyC was constructed with Ca2+-enhanced bactericidal activity against all S. aureus strains tested, including MRSA. Notably, treating S. aureus with 50 μg/mL of ClyC in the presence of 100 μM Ca2+ lead to a reduction of 9 Log10 (CFU/mL) in viable bacterial number, which was the first time to observe a lysin showing such a high activity. In addition, the effective concentration of ClyC could be decreased dramatically from 12 to 1 μg/mL by combination with 0.3 μg/mL of penicillin G. In a mouse model of S. aureus bacteremia, a single intraperitoneal administration of 0.1 mg/mouse of ClyC significantly improved the survival rates and reduced 2 Log10 (CFU/mL) of the bacterial burdens in the organs of the infected mice. ClyC was also found stable after lyophilization without cryoprotectants. Based on the above observations, ClyC could be a promising candidate against S. aureus infections. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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Review

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Review
Current Status of Endolysin-Based Treatments against Gram-Negative Bacteria
Antibiotics 2021, 10(10), 1143; https://doi.org/10.3390/antibiotics10101143 - 22 Sep 2021
Cited by 2 | Viewed by 1513
Abstract
The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization [...] Read more.
The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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