Characterization of a Lytic Bacteriophage vB_EfaS_PHB08 Harboring Endolysin Lys08 against Enterococcus faecalis Biofilms

Yang, Dan; Chen, Yibao; Sun, Erchao; Lin, Hua; Peng, Zhong; Wu, Bin

doi:10.3390/microorganisms8091332

Cited by 36 publications

(25 citation statements)

References 65 publications

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“…The bacteriophage lysin breaks down the peptidoglycan layer constituting the bacterial cell wall. Lysin has several advantages over traditional antibacterial drugs: (1) it has a completely different mechanism of action to conventional antibiotics, (2) it is expected to be advantageous in terms of safety as it has a very high selectivity for bacteria [ 5 ], (3) lysin also acts on bacteria in the state of biofilm formation [ 6 ], and (4) it is expected to have a low probability of developing resistant bacteria due to its high rate of action [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

LysSAP26, a New Recombinant Phage Endolysin with a Broad Spectrum Antibacterial Activity

Kim

Jin

Choi

et al. 2020

Viruses

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Multidrug-resistant (MDR) bacteria are a major threat to public health. Bacteriophage endolysins (lysins) are a promising alternative treatment to traditional antibiotics. However, the lysins currently under development are still underestimated. Herein, we cloned the lysin from the SAP-26 bacteriophage genome. The recombinant LysSAP26 protein inhibited the growth of carbapenem-resistant Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, oxacillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium with minimum inhibitory concentrations of 5~80 µg/mL. In animal experiments, mice infected with A. baumannii were protected by LysSAP26, with a 40% survival rate. Transmission electron microscopy analysis confirmed that LysSAP26 treatment resulted in the destruction of bacterial cell walls. LysSAP26 is a new endolysin that can be applied to treat MDR A. baumannii, E. faecium, S. aureus, K. pneumoniae, P. aeruginosa, and E. coli infections, targeting both Gram-positive and Gram-negative bacteria.

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Section: Introductionmentioning

confidence: 99%

LysSAP26, a New Recombinant Phage Endolysin with a Broad Spectrum Antibacterial Activity

Kim

Jin

Choi

et al. 2020

Viruses

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“…Using a MRSA strain SA14 as the indicator, we isolated a bacteriophage designated vB_Saus_PHB21 (thereafter referred as PHB21) from an epidermal sample collected from a Siberian tiger ( Panthera tigris altaica ) in Qingdao Zoo (Qingdao, China) through the conventional double-layer agar method, as described previously (13, 14). Phenotypically, PHB21 formed small round transparent plaques with a clear boundary in the double agar ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…A human origin MRSA strain SA14 was used as the indicator for bacteriophage isolation. Bacteriophage was isolated and purified according to methods described previously (13, 14). Phage morphology was observed using a 100-kV transmission electron microscope (HITACHI H-7650, Tokyo, Japan) with the same protocol as described by Chen et al (35).…”

Section: Methodsmentioning

confidence: 99%

“…After analysis through electrophoresis on a 1% agarose gel as well as a Qubit 2.0 (Thermo Scientific, Waltham, USA), a NEBNext Ultra™ ‖ DNA Library Prep Kit (NEB, Ipswich, USA) was used to prepare the sequence libraries, which were then sequenced on an Illumina NovaSeq 6000 platform (Novogene Co. LTD, Tianjin, China), using the pair-end 350 bp sequencing protocol. Raw reads with low quality were filtered as previously described (13, 14). High-quality reads were de novo assembled using SOAPdenovo2.04 with default parameters (38).…”

Section: Methodsmentioning

confidence: 99%

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A temperateSiphoviridaebacteriophage isolate from Siberian tiger enhances the virulence of Methicillin-resistantStaphylococcusaureus through distinct mechanisms

Yang

Wang

Sun

et al. 2021

Preprint

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The emergence and worldwide spread of Methicillin-resistant Staphylococcus aureus (MRSA) poses a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (Panthera tigris altaica) using a MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the Siphoviridae family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, cell invasion, anti-phagocytosis and biofilm formation. Challenge of the lysogenic strain (SA14+) caused severer mortalities in both Galleria mellonella and mouse models. Mice challenged with SA14+ showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-γ and TNF-α) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence and invasion to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of “bacteria-phage-interactions” in MRSA.IMPORTANCEThe interaction between bacteriophage and bacteria is like a “double-edged sword”: phages can either kill bacteria, or they may contribute to the bacterial fitness and virulence. In general, phages have positive impacts on bacterial fitness and virulence mainly because they carry antimicrobial resistance genes (ARGs) and/or virulence factors encoding genes (VFGs) and they can spread these harmful genes to the host bacteria. However, we found those phages which do not harbor ARGs and/or VFGs may also enhance the bacterial fitness and virulence. In addition, we also found the integration of phage genomes may lead to the upregulated expression of virulence associated genes in bacteria. Our study may provide new insights to redefine the relationship between phage and bacteria, and the results may also remind a cautious way to set phage-therapy for bacterial infections, before which the safety of a phage intends to be used should be fully evaluated.

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“…So, this study also suggested phage and endolysin as possible biocontrol agents that could destroy the biofilm formation of E. faecalis . Additionally, high stability of phages in different environmental conditions can increase their use in UTI [ 71 ]. Another interesting study on two-species biofilms investigated the effectiveness of hydrogel silicone urinary catheter treated with phage cocktail in inhibition of biofilm formation by a mixture of P. mirabilis and P. aeruginosa in an in vitro model using artificial urine.…”

Section: Phages Inhibition For Other Uropathogenic Bacterial Biofilmmentioning

confidence: 99%

Bacteriophage therapy for inhibition of multi drug‐resistant uropathogenic bacteria: a narrative review

Chegini¹,

Khoshbayan²,

Vesal³

et al. 2021

Ann Clin Microbiol Antimicrob

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Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage–host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.

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Characterization of a Lytic Bacteriophage vB_EfaS_PHB08 Harboring Endolysin Lys08 against Enterococcus faecalis Biofilms

Cited by 36 publications

References 65 publications

LysSAP26, a New Recombinant Phage Endolysin with a Broad Spectrum Antibacterial Activity

LysSAP26, a New Recombinant Phage Endolysin with a Broad Spectrum Antibacterial Activity

A temperateSiphoviridaebacteriophage isolate from Siberian tiger enhances the virulence of Methicillin-resistantStaphylococcusaureus through distinct mechanisms

Bacteriophage therapy for inhibition of multi drug‐resistant uropathogenic bacteria: a narrative review

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