Medical Microbiology and Immunology

, Volume 202, Issue 2, pp 153–165

Recombinant GroEL enhances protective antigen-mediated protection against Bacillus anthracis spore challenge

Original Investigation

DOI: 10.1007/s00430-012-0280-z

Cite this article as:
Sinha, K. & Bhatnagar, R. Med Microbiol Immunol (2013) 202: 153. doi:10.1007/s00430-012-0280-z

Abstract

The fatal inhalation infection caused by Bacillus anthracis results from a complex pathogenic cycle involving release of toxins by bacteria that germinate from spores. Currently available vaccines against anthrax consist of protective antigen (PA), one of the anthrax toxin components. However, these PA-based vaccines are only partially protective against spore challenge in mice. This shows that exclusive elicitation of high anti-PA titer does not directly correlate with protection. Here, we demonstrate that inclusion of GroEL of B. anthracis with PA elicits enhanced protection against anthrax spore challenge in mice. GroEL was included as it has been reported to be present both on the exosporium and in the secretome in addition to the cell surface of B. anthracis. It has also been found protective against other pathogens. In the present study, immunization with GroEL alone was also potent enough to induce high humoral and cell-mediated response and significantly prolonged the mean time to death in spore-challenged mice. As a surface antigen, opsonization of spores with anti-GroEL IgG showed increased uptake of treated spores and therefore accelerated rate of spore destruction by phagocytic cells leading to the protection of mice. We found that GroEL was able to enhance nitric oxide release from lymphocytes and also reduce bacterial load from the organs, probably through the activation of macrophages and over-expression of certain innate immunity receptors. Therefore, the present study emphasizes that GroEL is an effective immunomodulator against B. anthracis infection.

Keywords

Anthrax Heat-shock protein GroEL Spore uptake Bacterial clearance 

Abbreviations

BHI

Brain heart infusion

LeTx

Lethal toxin

EdTx

Edema toxin

TMB

3,3′,5,5′-Tetramethylbenzidine

MTT

3-(4,5-dimethyl thiazol-2-yl)-5diphenyl tetrazolium bromide

MTD

Mean time death

AVA

Anthrax vaccine adsorbed

PA

Protective antigen

LF

Lethal factor

EF

Edema factor

ASA

Anti-spore antiserum

PRR

Pattern recognition receptors

TNA

Toxin-neutralizing assay

EC50

Effective concentration 50

CD

Cluster of differentiation

NO

Nitric oxide

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Lab #122, Molecular Biology and Genetic Engineering Laboratory, School of BiotechnologyJawaharlal Nehru UniversityNew DelhiIndia

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