Induction of an outer surface protein on Borrelia burgdorferi during tick feeding.

Abstract

Lyme disease spirochetes, Borrelia burgdorferi sensu lato, are maintained in zoonotic cycles involving ticks and small mammals. In unfed ticks, the spirochetes produce one outer surface protein, OspA, but not OspC. During infection in mammals, immunological data suggest that the spirochetes have changed their surface, now expressing OspC but little or no OspA. We find by in vitro growth experiments that this change is regulated in part by temperature; OspC is produced by spirochetes at 32-370C but not at 24°C. Furthermore, spirochetes in the midgut of ticks that have fully engorged on mice now have OspC on their surface. Thus two environmental cues, an increase in temperature and tick feeding, trigger a major alteration of the spirochetal outer membrane. This rapid synthesis of OspC by spirochetes during tick feeding may play an essential role in the capacity of these bacteria to successfully infect mammalian hosts, including humans, when transmitted by ticks.Many infectious agents pathogenic in humans are maintained in natural zoonotic cycles involving wild vertebrates and obligate blood-feeding arthropods (1, 2). Although much is known about the clinical description and diagnosis of these human diseases, the physiological and morphological adaptations of these agents, especially bacteria, while in their arthropod vectors are not well understood. Several non-vector-borne bacterial pathogens, including species of Salmonella, Shigella, and Bordetella, display an impressive repertoire of adaptive molecular responses to environmental signals on entry into mammalian hosts (3-5). Specific changes by bacterial pathogens in arthropod vectors during feeding on blood have not been described. Identifying such events would broaden our knowledge of how these agents are perpetuated and transmitted in nature and assist in the development of effective vaccines and diagnostic tests.Borrelia burgdorferi is one of at least three closely related species of spirochetes that cause a spectrum of clinical syndromes in humans, collectively called Lyme disease or Lyme borreliosis (6-8). These spirochetes are maintained in zoonotic cycles involving a diversity of wild mammals and ticks primarily in the genus Ixodes (9). These microbes' adaptation to tick and mammalian environments likely involves very different surface components so as to ensure their transmission and survival in two very different hosts. Several lipoproteins have been described on the surface of B. burgdorferi (10)(11)(12)(13)(14)(15)(16), some of which are variably expressed during serial passage in culture (17)(18)(19). The apparent flexibility in the spirochete's synthesis of some outer surface proteins (Osps) in vitro may have relevance to its alternation of hosts. Previous studies demonstrate that B. burgdorferi produces one surface protein, OspA, and likely OspB, in the midgut of Ixodes ticks that have not yet engorged on blood (10). However, it is unclear how long spirochetes continue to produce this protein after entering mammalian hosts because few anim...

Biology of Infection with Borrelia burgdorferi

“…Also, the pH of mammalian tissue and blood is neutral, whereas the tick midgut is a more basic environment [47,48]. In order to cycle between two very different hosts, B. burgdorferi varies its gene expression, leading to different protein components and enabling physiological adaptation to these environments [49][50][51][52][53]. A number of studies have begun to delineate those changes.…”

“…Studies of B. burgdorferi factors required for mammalian and tick infection began with identifying changes in protein composition as the spirochete alternated between these disparate environments [49,51,92]. As microarray analysis was developed, this technique was applied to measuring differences in gene expression between bacteria grown in conditions that mimic some characteristics of each host environment [93][94][95].…”

“…OspC production begins in feeding ticks (or immediately after needle inoculation, Fig. 1) and lasts for the first couple of weeks of mammalian infection [49,51,103,[121][122][123]. Once the bacteria are established in a host, OspC production is not required for persistence [114].…”

“…The population of spirochetes expands [156][157][158] and their protein synthesis alters [49,99,122,159,160]. Then, spirochetes migrate from the midgut to the salivary glands, allowing transmission into a new host.…”

“…The B. burgdorferi outer surface protein OspA was shown to be abundant on the surface of bacteria resident in ticks (Fig. 1), but down-regulated during tick feeding and transmission to a mammal [49,160]. Subsequent studies suggest that OspA is an adhesin, important for retaining spirochetes in the tick midgut until feeding [161][162][163].…”