Vaccination with Recombinant Mycobacterium tuberculosis PknD Attenuates Bacterial Dissemination to the Brain in Guinea Pigs

Ciaran Skerry, Supriya Pokkali, Michael Pinn, Nicholas A. Be, Jamie Harper, Petros Karakousis, Sanjay Jain

Research output: Contribution to journalArticle

Abstract

Background:We have previously identified Mycobacterium tuberculosis PknD to be an important virulence factor required for the pathogenesis of central nervous system (CNS) tuberculosis (TB). Specifically, PknD mediates bacillary invasion of the blood-brain barrier, which can be neutralized by specific antisera, suggesting its potential role as a therapeutic target against TB meningitis.Methodology/Principal Findings:We utilized an aerosol challenge guinea pig model of CNS TB and compared the protective efficacy of recombinant M. tuberculosis PknD subunit protein with that of M. bovis BCG against bacillary dissemination to the brain. BCG vaccination limited the pulmonary bacillary burden after aerosol challenge with virulent M. tuberculosis in guinea pigs and also reduced bacillary dissemination to the brain (P = 0.01). PknD vaccination also offered significant protection against bacterial dissemination to the brain, which was no different from BCG (P>0.24), even though PknD vaccinated animals had almost 100-fold higher pulmonary bacterial burdens. Higher levels of PknD-specific IgG were noted in animals immunized with PknD, but not in BCG-vaccinated or control animals. Furthermore, pre-incubation of M. tuberculosis with sera from PknD-vaccinated animals, but not with sera from BCG-vaccinated or control animals, significantly reduced bacterial invasion in a human blood-brain barrier model (P

Original languageEnglish (US)
Article numbere66310
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 11 2013

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Mycobacterium tuberculosis
Mycobacterium bovis
guinea pigs
Brain
Guinea Pigs
Vaccination
Animals
vaccination
brain
Central Nervous System Tuberculosis
tuberculosis
blood-brain barrier
Neurology
animals
aerosols
blood serum
Aerosols
Blood-Brain Barrier
central nervous system
lungs

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Vaccination with Recombinant Mycobacterium tuberculosis PknD Attenuates Bacterial Dissemination to the Brain in Guinea Pigs. / Skerry, Ciaran; Pokkali, Supriya; Pinn, Michael; Be, Nicholas A.; Harper, Jamie; Karakousis, Petros; Jain, Sanjay.

In: PLoS One, Vol. 8, No. 6, e66310, 11.06.2013.

Research output: Contribution to journalArticle

Skerry, Ciaran ; Pokkali, Supriya ; Pinn, Michael ; Be, Nicholas A. ; Harper, Jamie ; Karakousis, Petros ; Jain, Sanjay. / Vaccination with Recombinant Mycobacterium tuberculosis PknD Attenuates Bacterial Dissemination to the Brain in Guinea Pigs. In: PLoS One. 2013 ; Vol. 8, No. 6.
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