Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector

Abstract

The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naïve mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naïve mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector.

Functional Equivalence of OspA and OspB, but Not OspC, in Tick Colonization by Borrelia burgdorferi

“…In contrast, OspB could substitute for OspA during tick colonization. Our data provide further evidence supporting the conclusion of Battisti et al (18) that a significant role of OspA is to protect spirochetes in the tick midgut from ingested mammalian antibodies, while we also demonstrate that OspA plays a significant role in tick colonization in the absence of specific antibody.…”

“…OspA is required for normal tick colonization (18)(19)(20). Previous studies have demonstrated that OspA binds to a tick midgut receptor (TROSPA) (21) and protects spirochetes from the tick midgut environment, including antibodies against invariant B. burgdorferi surface components entering with a blood meal from an infected animal (18).…”

“…Previous studies have demonstrated that OspA binds to a tick midgut receptor (TROSPA) (21) and protects spirochetes from the tick midgut environment, including antibodies against invariant B. burgdorferi surface components entering with a blood meal from an infected animal (18). OspB mutants have also been reported to be defective in tick colonization (22), but other data indicate that OspB serves a minor role in the infectious cycle, at least in a laboratory setting (18). OspC is required for early mammalian infection (23)(24)(25), and a recent study indicates that OspC blocks the phagocytosis of spirochetes by macrophages in the skin (26).…”

“…OspA is required for normal tick colonization (18)(19)(20). Previous studies have demonstrated that OspA binds to a tick midgut receptor (TROSPA) (21) and protects spirochetes from the tick midgut environment, including antibodies against invariant B. burgdorferi surface components entering with a blood meal from an infected animal (18). OspB mutants have also been reported to be defective in tick colonization (22), but other data indicate that OspB serves a minor role in the infectious cycle, at least in a laboratory setting (18).…”

Physiological Factors Affecting the Bactericidal Activity of the Western Fence Lizard (Sceloporus Occidentalis) for the Lyme Disease Spirochete, Borrelia Burgdorferi

“…Notable shifts include the down-regulation of surface protein ospA and the up-regulation of ospC (Marconi et al, 1993;Ohnishi et al, 2001;Schwan et al, 1995;Schwan and Piesman, 2000). OspA interacts with a protein in the tick gut to facilitate spirochete colonization in tick gut epithelium (Pal et al, 2004) and protects the spirochetes from host-derived bacteriacidal antibodies (Battisti et al, 2008). The upregulation of ospC reduces the effect of the host adaptive immune response to kill the spirochetes in the tick's midgut while feeding, effectively evading the host's immune system and aiding in dissemination; however, the precise mechanism is still unknown (Randolf and Caimano, 2008).…”