Depolymerase improves gentamicin efficacy during Klebsiella pneumoniae induced murine infection

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Date: Aug. 23, 2014
From: BMC Infectious Diseases(Vol. 14, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Article
Length: 6,366 words
Lexile Measure: 1510L

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Author(s): Shruti Bansal1 , Kusum Harjai1 and Sanjay Chhibber1

Background

Capsular polysaccharide (CPS) is a discrete layer tightly bound to the bacterial cell wall. It is a major virulence determinant in pathogens like Streptococcus pneumoniae , Neisseria meningitidis , Haemophilus influenzae , Klebsiella pneumoniae , Escherichia coli , Cryptococcus neoformans etc. [1-4]. It mediates adherence, protects bacteria against dessication, bacteriophages and immune response [5]. Strains possessing capsules can evade immune responses by several mechanisms. Firstly, their hydrophilic nature and net negative charge repel the negatively charged surface of phagocytes thereby diminishing bacterial removal through phagocytosis [6]. Secondly, capsular polysaccharides mask the pathogen-associated molecular patterns (PAMPs) that are recognised by Toll-like receptors (TLRs) thereby preventing activation of immune response [7, 8]. Thirdly, presence of capsule may cause deficient binding, degradation or masking of complement components [9]. In addition, encapsulated bacteria might be protected from various antimicrobial peptides (APs) present in mucosal surfaces [10].

Klebsiella pneumoniae is a common cause of nosocomial infections including urinary tract, respiratory, wound infections, bacteremia, septicemia, pyogenic liver abscess etc. [11]. K. pneumoniae CPS is antiphagocytic, mediates serum resistance and induces cytotoxicity during infection of lung epithelial cells. It also helps in bacterial colonization and biofilm formation at infection sites [12]. Of the 78 chemically distinct capsular types of K. pneumoniae, K1 and K2 are the most virulent. They have been frequently isolated from patients with bacteremia and respiratory tract infections [13, 14]. Aminoglycosides and fluoroquinolones have been widely used for restricting the growth of members of Enterobacteriaceae family. Antibiotics might kill the free-floating bacteria in vivo but fail to eradicate bacterial cells embedded in a biofilm [15]. The, bacterial CPS is known to interfere with the penetration of many antibiotics, leading to exposure of bacteria to sub-MIC concentrations, that increases the risk of resistance [16]. These mounting concerns underscore the need for an effective alternative treatment strategy for infections.

CPS is an excellent target for compounds aimed at replacing or supplementing antibiotic treatment for microbial infections. CPS synthesis can be blocked by deleting or downregulating the genes for capsule biosynthesis [5]. The therapeutic interventions include 'capsule-stripping' by using naturally occurring or engineered bacteria or bacteriophages that secrete pathogen-specific CPS-depolymerizing enzymes like lyase, glycosidase, endosialidase, polyglutamic acid depolymerase [5].

No report is available on the in vivo use of an enzyme derived from unrelated genera capable of decapsulating K. pneumoniae. In the present study, a Aeromonas punctata derived depolymerase was used to alter the severity of infection during K. pneumoniae induced pneumonia and septicemia. Enzyme treatment of this kind can provide several advantages during bacterial infections. They attenuate the virulence of denuded pathogen and improve its susceptibility to immune defences. They can also be useful as adjuncts to antibiotics for an early recovery from infection. Since they are not directly bactericidal they do not allow generation of resistant mutants and because they are highly specific so they do not target normal flora [17].

Methods

Bacterial strains, antibiotic

Klebsiella pneumoniae B5055 (O1:K2), obtained from Dr Mathia Trautmann, Department of Medical Microbiology...

Source Citation

Source Citation   

Gale Document Number: GALE|A539575165