How borrelia digests YOU

From: kathleen (kathleen.dickson_at_snet.net)
Date: 03/24/05 

Date: 24 Mar 2005 10:04:03 -0800

Infect Immun. 2005 Apr;73(4):2253-61. Related Articles, Links

The Thermophilic, Homohexameric Aminopeptidase of Borrelia burgdorferi
Is a Member of the M29 Family of Metallopeptidases.

Bertin PB, Lozzi SP, Howell JK, Restrepo-Cadavid G, Neves D, Teixeira
AR, de Sousa MV, Norris SJ, Santana JM.

Chagas' Disease Multidisciplinary Research Laboratory, Institute of
Biology, The University of Brasilia, 70.910-900 Brasilia DF, Brazil.
jsantana@unb.br.

Proteases are implicated in several aspects of the physiology of
microorganisms, as well as in host-pathogen interactions.
Aminopeptidases are also emerging as novel drug targets in infectious
agents. In this study, we have characterized an aminopeptidase from the
spirochete Borrelia burgdorferi, the causative agent of Lyme disease.
The aminopeptidolytic activity was identified in cell extracts from B.
burgdorferi by using the substrate leucine-7-amido-4-methylcoumarin. A
protein displaying this activity was purified from B. burgdorferi by a
two-step chromatographic procedure, yielding a approximately 300-kDa
homo-oligomeric enzyme formed by monomers of approximately 50 kDa. Gel
enzymography experiments showed that enzymatic activity depends on the
oligomeric structure of the protease but does not involve interchain
disulfide bonds. The enzyme was identified by peptide mass
fingerprinting as the putative aminopeptidase II of B. burgdorferi,
encoded by the gene BB0069. It shares significant identity to members
of the M29/T family of metallopeptidase, is sensitive to bestatin, has
a neutral pH optimum, and displays maximal activity at 60 degrees C.
Its activity is 1.75-fold higher at the temperature of the mammalian
host than at that of the insect host of the pathogen. The activity of
this thermophilic aminopeptidase of B. burgdorferi (TAP(Bb)) depends on
Zn(2+), and temperatures over 70 degrees C promoted its inactivation
through a transition from the hexameric state to the monomeric state.
Since B. burgdorferi is deficient in pathways for amino acid synthesis,
TAP(Bb) could play a role in supplying required amino acids.
Alternatively, the enzyme could be involved in peptide and/or protein
processing.

PMID: 15784569 [PubMed - in process]

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