Mechanism of Bacteriophage Lytic Enzyme in Phage Therapy against Streptococcal Infection by in Silico Approach
Abstract:
Lysins or Lytic enzymes of Bacteriophage
are highly evolved molecules produced to release their progeny by hydrolyzing the
bacterial host cell wall. Now days, due to Multi Drug Resistance in many streptococcal
infections; this mechanism is exploited as an alternative therapy against traditional
antibiotic therapy. But in the treatment of phage therapy the mode of action is
still unclear in the literatures. This study will evidence the probable mode of
mechanism by the lysin in the breakage of host cell wall by In Silico approach.
3-D structure of Lysin was retrieved from Protein Data Bank and structure of peptidoglycan
is retrieved from the PubChem. Docking studies was performed using Hex 6.3 taking
lysin as receptor and peptidoglycan as ligand. Results were visualized in PyMol
molecular visualization software. Docking studies showed the hydrophilic interaction
between the peptidoglycan and lysin. The interacting residue of lysin belongs to
CHAP domain which is responsible for the amidase catalytic activity which results
in the breakage of cell wall for the release of their progeny. Molecular interactions
between the lysin and peptidoglycan showed the possible mechanism for lysin which
is responsible for breaking the major bonds in peptidoglycan layer for the release
of bacteriophage progeny inside the host bacterial cell. This study will give the
further evidence for the mode of action and by understanding this mechanism further
improved therapies can be achieved in the Multi Drug Resistance bacterial infections.
Keywords: Bacteriophage,
Streptococcus spp, Multi
Drug Resistance bacterial infections, Lysin, Peptidoglycan, Docking studies.
References:
[1]. Berkowitz
FE. Antibiotic resistance in bacteria. South Med J 1995;88:797-804.
[2]. B.
Levin, J. Bull. Population and evolutionary dynamics of phage therapy. Nature
Reviews Microbiology 2004; 2: 166-173.
[3]. Hermoso
JA, Garcia JL, Garcia P. Taking aim on bacterial pathogens: From phage therapy
to enzybiotics. Curr Opin Microbiol 2007; 10:461-472.
[4]. Navarre
WW, Ton-That H, Faull KF, Schneewind O. Multiple enzymatic activities of the
murein hydrolase from staphylococcal phage phi11. Identification of a D-alanyl
–glycine endopeptidase activity. J Biol chem 1999; 274:15847-56.
[5]. Nelson
D, Schuch R, Chahales P, Zhu S, Fischetti VA . PlyC: A multimeric bacteriophage
lysine. Proc Natl Acad Sci USA 2006; 103:10765-70.
[6]. Pritchard
DG, Dong S, Baker JR, Engler JA. The bifunctional peptidoglycan lysine of
Streptococcus agalactiae bacteriophage B30. Microbiology 2004; 150:2079-87.
[7]. Stark
CJ, Hoopes JT, Bonocora RP, Nelson DC. Bacteriophage lytic enzymes as
antimicrobials. Bacteriophage in the Detection and control of Foodborne
Pathogens, eds Sabour PV, Griffith MW (ASM Press, Washington DC), 2010. pp
137-156.
[8]. Smith
H W, Huggins M B. Successful treatment of experimental E.coli infections in mice
using phage; its superiority over antibiotics. J Gen Microbio. 1982;
128:307-318.
[9]. S. Matsuzaki, M. Rashel, J. Uchiyama, S. Sakurai, T. Ujihara, M. Kuroda,
M. Ikeuchi,T. Tani, M. Fujieda, H.Wakiguchi, S. Imai, Bacteriophage therapy:
a revitalized therapy against bacterial infectious diseases. J. Infect.
Chemother. 2005; 11: 211-219.
[10]. Tenover
FC, Hughes JM. The challenges of emerging infectious diseases: development and
spread of multiply resistant bacterial pathogens. JAMA 1996; 275:300-4.
[11]. VinodKumar
C. S, Suneeta Kalsurmath, Neelagund Y.F. Utility of lytic bacteriophage in the
treatment of multidrug resistant Pseudomonas
aeruginosa septicemia in mice. Ind J Patho Microbiol 2008;51(3):360-366
[12]. VinodKumar
C. S, Suneeta Kalsurmath, Neelagund Y.F. Bacteriophage in the treatment of
experimental septicemic mice from a clinical isolate of multidrug resistant Klebsiella pneumoniae. J Commun Dis.
2005;37(3): 749-753
[13]. VinodKumar
C. S, Srinivasa H, Basavarajappa K.G, Nitin Bandekar. Isolation of
Bacteriophages for MRSA obtained from Diabetic foot- A Possible treatment
Option in infections. Inter J
Biotechnol Biochem. 2010; 6(5): 801-809.
[14]. VinodKumar
C. S, Srinivasa H, Basavarajappa K.G, Geethalakshmi S, Nitin Bandekar. Isolation of Bacteriophages to MDR Enterococci obtained
from Diabetic foot- A Novel antimicrobial agent
waiting in the Shelf?. Ind J Pathol Microbiol. 2011;54(1):90-96
[15]. VinodKumar
C. S, Srinivasa H, Basavarajappa K.G, Umakanth Patil, Nitin Bandekar, Rajashri
Patil. Abrogation of Staphylococcus
aureus wound infection by bacteriophage in diabetic rats. International
journal of pharmacy and drug research. 2011:3(3); 202-207
[16]. VinodKumar
C. S, Srinivasa H, Basavarajappa K.G, Umakanth Patil, Nitin Bandekar, Rajashri
Patil. Effectiveness of bacteriophage in the treatment of Staphylococcus aureus wound infection in the diabetic animal model.
Asian J Pharm Res. 2012;5:
123-127
[17]. Young
R. Bacteriophage lysis: Mechanism and regulation. Microbial Rev 1992; 56:430-481.