Relapsing fever spirochaetes produce a serine protease that provides

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Molecular Microbiology
Volume 60 Page 710 - May 2006
doi:10.1111/j.1365-2958.2006.05122.x
Volume 60 Issue 3

Relapsing fever spirochaetes produce a serine protease that provides
resistance to oxidative stress and killing by neutrophils

Cyril Guyard*, James M. Battisti, Sandra J. Raffel, Merry E. Schrumpf,
Adeline R. Whitney, Jonathan G. Krum§, Stephen F. Porcella, Patricia
A. Rosa, Frank
R. DeLeo and Tom G. Schwan

Summary

The spirochaetes that cause tick-borne relapsing fever and Lyme disease
are
closely related human pathogens, yet they differ significantly in their
ecology
and pathogenicity. Genome sequencing of two species of relapsing fever
spirochaetes, Borrelia hermsii and Borrelia turicatae, identified a
chromosomal open
reading frame, designated bhpA, not present in the Lyme disease
spirochaete
Borrelia burgdorferi. The predicted amino acid sequence of bhpA was
homologous
with the HtrA serine proteases, which are involved with stress
responses and
virulence in other bacteria. B. hermsii produced an active serine
protease that
was recognized by BhpA antibodies and the recombinant BhpA
protein-degraded
ß-casein. bhpA was transcribed in vitro at all growth temperatures and

transcription levels were slightly elevated at higher temperatures.
These results
correlated with the synthesis of BhpA during B. hermsii infection in
mice. With
the exception of Borrelia recurrentis, the bhpA gene, protein and
enzymatic
activity were found in all relapsing fever spirochaetes, but not in
Lyme disease
or related spirochaetes. Heterologous expression of bhpA in B.
burgdorferi
increased the spirochaete's resistance to both oxidative stress and
killing by
human neutrophils. Therefore, we propose that bhpA encodes a unique and

functional serine protease in relapsing fever spirochaetes. This
periplasmic enzyme may
prevent the accumulation of proteins damaged by the innate immune
response
and contribute to the ability of the relapsing fever spirochaetes to
achieve
high cell densities in blood.

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