This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural
infection cycle, which alternates between ticks and small mammals.
OspC is a major
surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking
OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for
OspC by using an
ospC mutant complemented with an unstable copy of the
ospC gene and show that B. burgdorferi's requirement for
OspC is specific to the mammal and limited to a critical early stage of mammalian
infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented
ospC mutant strain no longer carried the wild-type copy of
ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these
ospC mutant spirochetes did not infect naive mice.
ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by
tissue transplantation. We conclude that
OspC is indispensable for establishing
infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick
infection cycle.