Phage-Encoded Endolysins

Abdelrahman, Fatma; Easwaran, Maheswaran; Daramola, Oluwasegun I.; Ragab, Samar; Lynch, Stephanie A; Oduselu, Tolulope J.; Khan, Fazal Mehmood; Ayobami, Akomolafe; Adnan, Fazal; Torrents, Eduard; Sanmukh, Swapnil Ganesh; El‐Shibiny, Ayman

doi:10.3390/antibiotics10020124

Cited by 119 publications

(131 citation statements)

References 177 publications

(178 reference statements)

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…Numerous endolysin studies confirm the in vitro effectiveness of these enzymes and describe valuable advantages of their use to combat multiple Gram-positive or -negative bacterial pathogens. However, very few of the studies are devoted to in vivo application and just several molecules are in clinical trials ( Abdelrahman et al, 2021 ; Grabowski et al, 2021 ; Schmelcher and Loessner, 2021 ). Such a trend does not promote the acceleration of the development and implication of endolysin-based drugs into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections

et al. 2021

View full text Add to dashboard Cite

Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g., ESKAPE group bacteria, which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, and are highly inclined to gain multiple antibiotic resistance. Despite numerous works devoted to the screening of new lytic enzymes and investigations of their biochemical properties, there are significant breaches in some aspects of their operating characteristics, including safety issues of endolysin use. Here, we provide a comprehensive study of the antimicrobial efficacy aspects of four Gram-negative bacteria-targeting endolysins LysAm24, LysAp22, LysECD7, and LysSi3, their in vitro and in vivo activity, and their biological safety. These endolysins possess a wide spectrum of action, are active against planktonic bacteria and bacterial biofilms, and are effective in wound and burn skin infection animal models. In terms of safety, these enzymes do not contribute to the development of short-term resistance, are not cytotoxic, and do not significantly affect the normal intestinal microflora in vivo. Our results provide a confident base for the development of effective and safe candidate dosage forms for the treatment of local and systemic infections caused by Gram-negative bacterial species.

show abstract

Section: Discussionmentioning

confidence: 99%

Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In contrast to whole-phage preparations, isolated natural and genetically engineered enzymes of Proteus phages (endolysins, polysaccharide depolymerases) have not been intensively investigated as antibacterial agents, especially in comparison with other Gram-negative pathogens [ 63 , 64 , 65 ]. In a recent work, Alves et al reported that the majority of Proteus phages they studied produced clear plaques surrounded by haloes, which is a well-known characteristic of phage depolymerase activity; despite that, the authors were unable to identify the ORFs encoding potential depolymerases in the genomes of the bacteriophages they sequenced [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Phage-Derived Depolymerase with Activity against Proteus mirabilis Biofilms

et al. 2021

View full text Add to dashboard Cite

The adherence of Proteus mirabilis to the surface of urinary catheters leads to colonization and eventual blockage of the catheter lumen by unique crystalline biofilms produced by these opportunistic pathogens, making P. mirabilis one of the leading causes of catheter-associated urinary tract infections. The Proteus biofilms reduce efficiency of antibiotic-based treatment, which in turn increases the risk of antibiotic resistance development. Bacteriophages and their enzymes have recently become investigated as alternative treatment options. In this study, a novel Proteus bacteriophage (vB_PmiS_PM-CJR) was isolated from an environmental sample and fully characterized. The phage displayed depolymerase activity and the subsequent genome analysis revealed the presence of a pectate lyase domain in its tail spike protein. The protein was heterologously expressed and purified; the ability of the purified tail spike to degrade Proteus biofilms was tested. We showed that the application of the tail spike protein was able to reduce the adherence of bacterial biofilm to plastic pegs in a MBEC (minimum biofilm eradication concentration) assay and improve the survival of Galleria mellonella larvae infected with Proteus mirabilis. Our study is the first to successfully isolate and characterize a biofilm depolymerase from a Proteus phage, demonstrating the potential of this group of enzymes in treatment of Proteus infections.

show abstract

“…Phages, as well as their derivative enzymes, provide potential means for the development of treatment methods for future phage therapies [ 128 ]. Evidence indicates that enzymes from the isolated Streptococcus and Chlamydia phages can target S. agalactiae and C. trachomatis to impact their growth.…”

Section: Challenges Associated With Application Of Phage Therapy In Bacterial Sexually Transmitted Infectionsmentioning

confidence: 99%

Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections

et al. 2021

View full text Add to dashboard Cite

Bacterial sexually transmitted infections (BSTIs) are becoming increasingly significant with the approach of a post-antibiotic era. While treatment options dwindle, the transmission of many notable BSTIs, including Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum, continues to increase. Bacteriophage therapy has been utilized in Poland, Russia and Georgia in the treatment of bacterial illnesses, but not in the treatment of bacterial sexually transmitted infections. With the ever-increasing likelihood of antibiotic resistance prevailing and the continuous transmission of BSTIs, alternative treatments must be explored. This paper discusses the potentiality and practicality of phage therapy to treat BSTIs, including Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Streptococcus agalactiae, Haemophilus ducreyi, Calymmatobacterium granulomatis, Mycoplasma genitalium, Ureaplasma parvum, Ureaplasma urealyticum, Shigella flexneri and Shigella sonnei. The challenges associated with the potential for phage in treatments vary for each bacterial sexually transmitted infection. Phage availability, bacterial structure and bacterial growth may impact the potential success of future phage treatments. Additional research is needed before BSTIs can be successfully clinically treated with phage therapy or phage-derived enzymes.

show abstract

Phage-Encoded Endolysins

Cited by 119 publications

References 177 publications

Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections

Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections

Novel Phage-Derived Depolymerase with Activity against Proteus mirabilis Biofilms

Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections

Contact Info

Product

Resources

About