Silviavirus phage ɸMR003 displays a broad host range against methicillin-resistant Staphylococcus aureus of human origin

Peng, Chanthol; Hanawa, Tomoko; Azam, Aa Haeruman; LeBlanc, Cierra; Ung, Porsry; Matsuda, Takeshi; Onishi, Hiroaki; Miyanaga, Kazuhiko; Tanji, Yasunori

doi:10.1007/s00253-019-10039-2

Cited by 38 publications

(47 citation statements)

References 61 publications

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“…Our study agreed with prior work demonstrating S. aureus phages have broad host ranges (28)(29)(30)(31)(32)(33)(34). A major goal of our work was to prototype predictive models for host range based on genome sequence.…”

Section: Discussionsupporting

confidence: 87%

“…In addition, although many S. aureus phages are reported to have wide host ranges (28)(29)(30)(31)(32)(33)(34), and even early studies suggested staphylococcal phage therapies to be highly effective (35), experiments conducted thus far have failed to explain the genetic bases of host range or resistance development in a species-wide manner. Only one previous study has associated genetic factors (gene families) with phage resistance using a hypothesis-free method (36).…”

Section: S Aureus Phages and Corresponding Known Host Mechanisms Regmentioning

confidence: 99%

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Genes influencing phage host range in Staphylococcus aureus on a species-wide scale

Moller

Davis

Winston

et al. 2020

Preprint

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Staphylococcus aureus is a human pathogen that causes serious diseases ranging from skin infections to septic shock. Bacteriophages (“‘phages”‘) are both natural killers of S. aureus, offering therapeutic possibilities, as well as important vectors of horizontal gene transfer in the species. Here, we used high-throughput approaches to understand the genetic basis of strain-to-strain variation in sensitivity to phages, which defines the host range. We screened 259 diverse S. aureus strains covering more than 40 sequence types for sensitivity to eight phages, which were representatives of the three phage classes that infect the species. The phages were variable in host range, each infecting between 73 and 257 strains. Using genome-wide association approaches, we identified putative loci that affect host range and validated their function using USA300 transposon knockouts. In addition to rediscovering known host range determinants, we found several genes previously unreported genes affecting phage infection, including trpA, phoR, isdB, sodM, fmtC, and relA. We used the data from our host range matrix to develop predictive models that achieved between 40 and 95% accuracy. This work illustrates the complexity of the genetic basis for phage susceptibility in S. aureus but also shows that with more data, we may be able to understand much of the variation. With a knowledge of host range determination, we can rationally design phage therapy cocktails that target the broadest host range of S. aureus strains and address basic questions regarding phage-host interactions, such as the impact of phage on S. aureus evolution.ImportanceStaphylococcus aureus is a widespread, hospital- and community-acquired pathogen, many strains of which are antibiotic resistant. It causes diverse diseases ranging from local to systemic infection and affects both the skin and many internal organs, including the heart, lungs, bones, and brain. Its ubiquity, antibiotic resistance, and disease burden make new therapies urgent. One alternative therapy to antibiotics is phage therapy, in which viruses specific to infecting bacteria clear infection. In this work, we identify and validate S. aureus genes that influence phage host range - the number of strains a phage can infect and kill - by testing strains representative of the diversity of the S. aureus species for phage host range and associating strain’s genome sequences with host range. These findings together improve our understanding of how phage therapy works in the bacterium and improve prediction of phage therapy efficacy based on the infecting strain’s predicted host range.

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Section: Discussionsupporting

confidence: 87%

Section: S Aureus Phages and Corresponding Known Host Mechanisms Regmentioning

confidence: 99%

Genes influencing phage host range in Staphylococcus aureus on a species-wide scale

Moller

Davis

Winston

et al. 2020

Preprint

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“…Bacteriophages can be isolated from urban sewage (Maszewska & Różalski, 2019), the success of phage therapy is highly dependent on an isolated phage possessing a wide host range (Peng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of six gamma-irradiated bacteriophages specific for MRSA and VRSA isolated from skin infections

Mahmoud

Ahmed

Abo-Senna

et al. 2021

Journal of Radiation Research and Applied Sciences

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Although skin infections are usually uncomplicated, it may indicate systemic disease or lead to life-threatening systemic infections. Staphylococcus aureus is the most common cause of skin infections. Treatment is complicated by continuous emergence of resistant S. aureus especially methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Therefore, searching for new alternatives is essential to combat this escalating antibiotic resistance. Bacteriophage therapy is a promising solution in the post antibiotic area. Bacteriophage therapy confers safety and higher rate of success. In the present study, 10 bacteriophages (belonging to the family Siphoviridae and Myoviridae) were isolated with lytic activity against MRSA &VRSA isolated from skin infections. The strongest six of ten phages were characterized morphologically by a JOEL_JEM_1010 electron microscope, physically through evaluating their lytic activity against wide ranges of temperature (35-95° C), PH (3-10) and radiation doses (0.5-2.5kGy) and biologically by evaluating their host ranges and phage longevity (1-120 day) in vitro. Finally, the anti-Staphylococcal effect of the isolated bacteriophages was tested and revealed that they have alone activity (10, 12) and synergistic activity with vancomycin and erythromycin by increasing their inhibition zone diameters (16, 22) mm, respectively.

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“…Therefore, researchers are developing novel methods such as phage therapy. 87,88 In a study, Seth et al developed a skin lesion in the New Zealand rabbit ear and inoculated S. aureus to form a biofilm in the wound site. The wounds were treated locally with debridement, S. aureus-specific bacteriophage, and a combination of debridement and S. aureus-specific bacteriophage.…”

Section: Staphylococcus Aureusmentioning

confidence: 99%

<p>Bacteriophages, a New Therapeutic Solution for Inhibiting Multidrug-Resistant Bacteria Causing Wound Infection: Lesson from Animal Models and Clinical Trials</p>

Moghadam¹,

Khoshbayan²,

Chegini³

et al. 2020

DDDT

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Wound infection kills a large number of patients worldwide each year. Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most important colonizing pathogens of wounds that, with various virulence factors and impaired immune system, causes extensive tissue damage and nonhealing wounds. Furthermore, the septicemia caused by these pathogens increases the mortality rate due to wound infections. Because of the prevalence of antibiotic resistance in recent years, the use of antibiotics to inhibit these pathogens has been restricted, and the topical application of antibiotics in wound infections increases antibiotic resistance. Therefore, finding a new therapeutic strategy against wound infections is so essential since these infections have a destructive effect on the patient's mental health and high medical costs. In this review, we discussed the use of phages for the prevention of multidrug-resistant (MDR) bacteria, causing wound infection and their role in wound healing in animal models and clinical trials. The results showed that phages have a high ability to inhibit different wound infections caused by MDR bacteria, heal the wound faster, have lower side effects and toxicity, destroy bacterial biofilm, and they are useful in controlling immune responses. Many studies have used animal models to evaluate the function of phages, and this study appears to have a positive impact on the use of phages in clinical practice and the development of a new therapeutic approach to control wound infections, although there are still many limitations.

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Silviavirus phage ɸMR003 displays a broad host range against methicillin-resistant Staphylococcus aureus of human origin

Cited by 38 publications

References 61 publications

Genes influencing phage host range in Staphylococcus aureus on a species-wide scale

Genes influencing phage host range in Staphylococcus aureus on a species-wide scale

Isolation and characterization of six gamma-irradiated bacteriophages specific for MRSA and VRSA isolated from skin infections

<p>Bacteriophages, a New Therapeutic Solution for Inhibiting Multidrug-Resistant Bacteria Causing Wound Infection: Lesson from Animal Models and Clinical Trials</p>

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