Construction and characterization of a chimeric lysin ClyV with improved bactericidal activity against Streptococcus agalactiae in vitro and in vivo

Huang, Li; Luo, Dehua; Gondil, Vijay Singh; Gong, Yujing; Jia, Minghui; Ding, Yan; He, Jin; Shou-song, HU; Yang, Hang; Wei, Hongping

doi:10.1007/s00253-019-10325-z

Cited by 24 publications

(18 citation statements)

References 43 publications

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“…Endolysin renders numerous advantages over other alternative antibacterial agents, including high activity against drug-resistant pathogens, low chances of resistance, and high specificity towards target bacterium (Loessner et al, 2002;Schuch et al, 2002;Fischetti, 2008;Briers et al, 2009). Several endolysin have been reported to harbor broad-spectrum activity against Gram-positive bacteria in vitro and in vivo, such as PlyC (Nelson et al, 2006), ClyR (Yang et al, 2015a), Cpl-1 (Loeffler et al, 2003), ClyJ (Yang et al, 2020), and ClyV (Huang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Khan

Gondil

et al. 2021

Front. Cell. Infect. Microbiol.

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The rapid spread and emergence of multidrug-resistant Acinetobacter baumannii and other pathogenic Gram-negative bacteria spurred scientists and clinicians to look for alternative therapeutic agents to conventional antibiotics. In the present study, an A. baumannii bacteriophage p54 was isolated and characterized. Morphological and genome analysis revealed that bacteriophage p54 belongs to Myoviridae family with a genome size of 165,813 bps. A novel endolysin, namely LysAB54, showing low similarity with other well-known related endolysins, was cloned, expressed, and characterized from the bacteriophage p54. LysAB54 showed significant bactericidal activity against multidrug-resistant A. baumannii and other Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, in the absence of outer membrane permeabilizers. Based on all those observations, LysAB54 could represent a potential agent for the treatment of multidrug-resistant Gram-negative superbugs.

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Section: Introductionmentioning

confidence: 99%

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Khan

Gondil

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Considered a concerning threat by CDC, clindamycin resistance prevalent, some erythromycin, azithromycin and vancomycin resistance reported [5] Considered a part of normal flora for 10-30% of women [55], the CDC estimates 27,000 severe cases of GBS infections in the US, with 49% (~13,230) being erythromycin-resistant and with 28% (~7560) being clindamycin-resistant [5]; a majority of infants colonized with GBS do not develop a GBS infection; about 60% of cases of early-onset GBS infection occur in neonates born to patients with negative GBS culture at 35-37 weeks [56] Leading cause of neonatal sepsis and meningitis [55]; asymptomatic in colonized women [57] Intravenous penicillin G (during labor); ampicillin or vancomycin may be substituted [56] Gram-positive, with ten different capsular types (Ia, Ib, II-XI) [58] Growth observed with normal laboratory conditions (37 • C and enriched media) [59,60] Temperate phages have been isolated and characterized for S. agalactiae [59,61,62]; phage lysins have successfully shown activity in vitro (lysins from S. agalactiae phages B30 [63,64], λSA2 [65] and λSA1 [66], as well as CHAP k lysin derived from S. aureus [67]) and in vivo (PlyGBS from phage NCTC11261 [68] and chimeric ClyV [69]). There can be a wide host range with streptococcal phages and phage enzymes [70,71]…”

Section: Neisseria Gonorrhoeaementioning

confidence: 99%

“…In addition, in vivo analysis demonstrates the use of lysin PlyGBS derived from S. agalactiae phage NCTC 11261 in the reduction of GBS colonizing the vagina and oropharynx in mice [ 68 ]. Chimeric ClyV lysin (obtained by fusion of the enzymatically active domain from PlyGBS lysin and the cell wall binding domain from PlyV12 lysin) presented improved bactericidal activity in vitro and protected mice from lethal infection caused by intraperitoneal injection of S. agalactaie with a good safety profile [ 69 ]. Streptococcus agalactiae holds a great deal of potential for use in enzymatic phage therapy for many reasons, as it is Gram-positive, it only has lysogenic bacteriophages characterized, its topical application of phage enzyme preparations has reasonable support and GBS only becomes problematic when a woman is pregnant.…”

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

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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.

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“…The engineered lysin has shown better bactericidal activity than the parental enzyme and a single intraperitoneal dose of 0.1 mg of ClyV was able to provide 100% protection against S. agalactiae infection in experimental mouse models, thus demonstrating the potential role of this chimeric lysin against antibiotic resistant beta hemolytic streptococcal infections. 222 The engineered LysH5 lysin was studied for its potential to kill S. aureus persister cells with 100% efficacy at a minimum concentration of 0.15 µM. 205 …”

Section: Introductionmentioning

confidence: 99%

How Good are Bacteriophages as an Alternative Therapy to Mitigate Biofilms of Nosocomial Infections

Singh¹,

Padmesh²,

Dwivedi³

et al. 2022

IDR

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Bacteria survive on any surface through the generation of biofilms that provide a protective environment to grow as well as making them drug resistant. Extracellular polymeric matrix is a crucial component in biofilm formation. The presence of biofilms consisting of common opportunistic and nosocomial, drug-resistant pathogens has been reported on medical devices like catheters and prosthetics, leading to many complications. Several approaches are under investigation to combat drug-resistant bacteria. Deployment of bacteriophages is one of the promising approaches to invade biofilm that may expose bacteria to the conditions adverse for their growth. Penetration into these biofilms and their destruction by bacteriophages is brought about due to their small size and ability of their progeny to diffuse through the bacterial cell wall. The other mechanisms employed by phages to infect biofilms may include their relocation through water channels to embedded host cells, replication at local sites followed by infection to the neighboring cells and production of depolymerizing enzymes to decompose viscous biofilm matrix, etc. Various research groups are investigating intricacies involved in phage therapy to mitigate the bacterial infection and biofilm formation. Thus, bacteriophages represent a good control over different biofilms and further understanding of phage-biofilm interaction at molecular level may overcome the clinical challenges in phage therapy. The present review summarizes the comprehensive details on dynamic interaction of phages with bacterial biofilms and the role of phage-derived enzymes – endolysin and depolymerases in extenuating biofilms of clinical and medical concern. The methodology employed was an extensive literature search, using several keywords in important scientific databases, such as Scopus, Web of Science, PubMed, ScienceDirect, etc. The keywords were also used with Boolean operator “And”. More than 250 relevant and recent articles were selected and reviewed to discuss the evidence-based data on the application of phage therapy with recent updates, and related potential challenges.

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Construction and characterization of a chimeric lysin ClyV with improved bactericidal activity against Streptococcus agalactiae in vitro and in vivo

Cited by 24 publications

References 43 publications

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections

How Good are Bacteriophages as an Alternative Therapy to Mitigate Biofilms of Nosocomial Infections

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