Uninfected larval ticks acquire B. burgdorferi after feeding on a vector-competent host, and spirochetes colonize and persist within the tick midgut for months as the

tick molts to the nymphal stage [1]. In the infected-unfed tick, B. burgdorferi is associated with the midgut epithelium, existing in a non-replicative state in a nutrient poor environment. When infected nymphs begin to feed, the number of spirochetes increases as nutrients required for growth become more abundant [2]. The spirochetes move from the midgut of the feeding tick to the hemolymph and then to the salivary glands where they can be transferred to a naïve host, a process that occurs no earlier than 24 hours after tick attachment [3]. Small rodents or birds learn more are the primary reservoirs of B. burgdorferi; however, I. scapularis GSK2126458 cell line occasionally transmits the bacterium to larger vertebrates, including humans [1]. Upon infection in humans, spirochetes disseminate from the site of inoculation and may move to tissues other than the skin resulting in numerous clinical manifestations [1]. Symptoms of the primary infection are typically observed days to weeks after the tick bite and include flu-like symptoms that may be accompanied by a macular rash known as erythema migrans. If left untreated other symptoms may present months after inoculation, resulting in arthritis, myocarditis, and/or lesions

of the peripheral and central nervous systems [1]. While B. burgdorferi has evolved to survive in vastly different environments, it has limited biosynthetic capabilities and must obtain most nutrients from its surrounding environment [4, 5]. N-acetylglucosamine

(GlcNAc) is an essential component of peptidoglycan, the rigid layer responsible for strength of the microbial cell wall. Many bacteria can synthesize GlcNAc de novo; however, B. burgdorferi must import GlcNAc as a monomer or dimer (Tipifarnib order chitobiose) for cell wall synthesis and energy. Therefore, B. burgdorferi is normally Angiogenesis inhibitor cultured in vitro in the presence of free GlcNAc [6]. In the tick much of the GlcNAc is polymerized in the form of chitin, as this is the major component of the tick exoskeleton. In addition, chitin is an integral part of the peritrophic matrix that encases the blood meal during and after tick feeding. This membrane functions as a permeability barrier, enhances digestion of the blood meal, and protects the tick midgut from toxins and pathogens [7]. GlcNAc oligomers released during remodeling of the peritrophic matrix may be an important source of GlcNAc for B. burgdorferi in the nutrient limiting environment of the unfed-infected tick midgut [8]. Previous reports have demonstrated that Borrelia species cannot reach high cell densities in vitro when cultured without free GlcNAc [6, 9]. Recent reports by Tilly et al [10, 11] extended this work in B. burgdorferi with three significant findings.