Liposome loaded phage cocktail: Enhanced therapeutic potential in resolving Klebsiella pneumoniae mediated burn wound infections
Introduction
Nosocomial infections due to Klebsiella pneumoniae are a major cause of morbidity and mortality among burn patients [1]. It is an important pathogen that accounts for 15.2% of all burn wound infections caused by gram-negative bacteria [2]. The propensity of this organism to disseminate promptly leaves little time to institute effective antimicrobial treatment. Moreover, with its ability to develop resistance to commonly employed antibiotics, management of K. pneumoniae especially in burn patients has become challenging [3]. Due to the inexorable spread of antibiotic resistant-bacteria and lack of development of new antibiotics, there is an urgent need to explore newer therapeutic options against this pathogen.
Phage therapy represents a safe and potent alternative strategy against drug resistant pathogens [4], [5]. Although success in the therapeutic use of bacteriophages for treating various bacterial infections has already been substantiated by many workers [6], [7], [8], [9] in the past but till date, none of the phage based therapies have successfully made it to the market. The intrinsic disadvantages associated with phage therapy need to be examined for its clinical success in near future. The major drawbacks include: high specificity, making them narrow range antibacterial agents [10], rapid clearance of phages by reticuloendothelial system of our body, poor pharmacokinetic profile that negatively affects the potency of treatment [11], [12]. Thirdly, most of the phage protection studies in animals have been performed with phages being administered immediately following bacterial infection, which is not the situation in a clinical setting [13].
In the present study, two major issues associated with phage therapy i.e. narrow host range and rapid clearance have been addressed by employing (i) phage cocktail (rather than monophage therapy) and (ii) suitable lipid based phage delivery system i.e. liposomes for enhancing the viability and stability of bacteriophages, both in vitro as well as in vivo. Among the plethora of delivery systems, liposomes are one of the most intensively employed system due to their nontoxic nature, biocompatibility with phages, non-immunogenic effect and GRAS status (generally regarded as safe) [14]. The present study for the first time provides information on the application of liposome encapsulated lytic phage cocktail for treating burn wound infection.
Section snippets
Bacterial strains
K. pneumoniae B5055 was used in the present study. It was procured from Dr. Matthias Trautmann, Department of Medical Microbiology and Hygiene, Ulm, Germany. Clinical isolates of K. pneumoniae were procured from Post Graduate Institute of Medical Education and Research (PGIMER) and Government Medical College and Hospital (GMCH-32) Chandigarh, India. Morphological and biochemical properties of the isolates were identified according to Bergey’s Manual of Systematic Bacteriology [15]. The strains
Preparation of liposomes
The liposomal vesicles encapsulating phage cocktail were prepared and DLS measurements of their size and polydispersity index performed. The results for size distribution indicated that liposomal formulation having PC: CHOL: T-80: SA in a ratio of 8:2:1:0.5 showed mean diameter of 229.83 nm for a PI value of 0.259. Phage cocktail encapsulation efficiency in the lipid vesicles was high (79.2% ± 5.6), probably because of positively charged surfactant stearyl amine that led to increase in the
Discussion
Therapeutic application of bacteriophages to control bacterial infections has rekindled interest in phage therapy as an alternative treatment option for eradicating drug resistant bacterial pathogens [6], [7], [9]. However, it still suffers from issues of poor stability, narrow spectrum and poor pharmacokinetic profile. There is a need to look into the use of Drug Delivery Systems (DDS) for stable and efficient delivery of lytic self-propagating bacterial viruses so as to circumvent associated
Conflict of interest
The authors report no conflict of interest.
Acknowledgement
The financial grant received from the Indian Council of Medical Research (ICMR), New Delhi, India, is gratefully acknowledged.
References (38)
- et al.
Colonization of burn wounds in Ain Shams University Burn Unit
Burns
(2003) - et al.
Rapid acquisition of decreased carbapenem susceptibility in a strain of Klebsiella pneumoniae arising during meropenem therapy
Clin Microbiol Infect
(2012) - et al.
Bacteriophage host range and bacterial resistance
Adv Appl Microbiol
(2010) - et al.
Characterization of the drug retention and pharmacokinetic properties of liposomal nanoparticles containing dihydrosphingomyelin
Biochim Biophys Acta
(2007) Is half-life of circulating liposomes determined by changes in their permeability?
FEBS Lett
(1982)- et al.
Liposomal delivery system enhances anti-inflammatory properties of curcumin
J Pharm Sci
(2012) - et al.
Multi drug resistant Klebsiella isolates in burn patients: a comparative study
J Clin Diagn Res
(2015) - et al.
Bacteriophages as antibacterial agents
Harefuah
(2004) - et al.
Therapeutic potential of bacteriophage in treating Klebsiella pneumoniae B5055-mediated lobar pneumonia in mice
J Med Microbiol
(2008) - et al.
Efficacy of bacteriophage treatment in murine burn wound infection induced by Klebsiella pneumoniae
J Microbiol Biotechnol
(2009)
Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA) from diabetic foot infections
PLoS One
Evaluation of the efficacy of a bacteriophage in the treatment of pneumonia induced by multidrug resistance Klebsiella pneumoniae in mice
Biomed Res Int
Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics mediates effective resolution of Klebsiella pneumoniae induced lobar pneumonia
J Infect Dis
Long-circulating bacteriophage as antibacterial agents
Proc Natl Acad Sci U S A
Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections
Antimicrob Agents Chemother
Dynamics of success and failure in phage and antibiotic therapy in experimental infections
BMC Microbiol
Bergey’s manual of systematic bacteriology
Phage therapy of local and systemic disease caused by Vibrio vulnificus in iron-dextran-treated mice
Infect Immun
Bacteriophages
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