Study of the Response Regulator Rrp1 Reveals Its Regulatory Role in Chitobiose Utilization and Virulence of Borrelia burgdorferi

Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York.
Infection and immunity (Impact Factor: 3.73). 03/2013; 81(5). DOI: 10.1128/IAI.00050-13
Source: PubMed


Life cycle alternating between arthropod and mammals forces the Lyme disease spirochete, Borrelia burgdorferi, to adapt to different host milieus by utilizing diverse carbohydrates. Glycerol and chitobiose are abundantly present in the Ixodes tick. B. burgdorferi can utilize glycerol as a carbohydrate source for glycolysis and chitobiose to produce N-acetylglucosamine (GlcNAc), a key component of bacterial cell wall. A recent study reports that Rrp1, a response regulator that synthesizes cyclic diguanylate (c-di-GMP), governs glycerol utilization in B. burgdorferi. In this report, we found that the rrp1 mutant had growth defects and formed membrane blebs that led to cell lysis when GlcNAc was replaced by chitobiose in the growth medium. The gene chbC encodes a key chitobiose transporter of B. burgdorferi. We found that the expression level of chbC was significantly repressed in the mutant and that constitutive expression of chbC in the mutant successfully rescued the growth defect, indicating a regulatory role of Rrp1 on chitobiose uptake. Immunoblotting and transcriptional studies revealed that Rrp1 is required for the activation of bosR and rpoS and its impact on chbC is most likely mediated by the BosR-RpoS regulatory pathway. Tick-mouse infection studies showed that although the rrp1 mutant failed to establish infection in mice via tick bite, exogenous supplementation of GlcNAc into unfed ticks partially rescued the infection. The finding reported here provides us with new insight into the regulatory role of Rrp1 in carbohydrate utilization and virulence of B. burgdorferi.

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    • "Disparate infectivity results were obtained with two mutants in the gene encoding the fructose-mannose specific IIB component FruA-2, so further analysis is needed. The Chb system is thought to play important roles in the utilization of chitobiose during infection of ticks (Tilly et al., 2001; Rhodes et al., 2010; Sze et al., 2013). Not surprisingly, inactivation of the genes encoding the chitobiose-specific components ChbA and ChbC did not affect mouse infection by needle inoculation in our system. "
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    • "Rrp1 was also shown to regulate chitobiose utilization in vitro in B. burgdorferi. Furthermore, these mutants were unable to transmit to mice via tick bite unless the ticks were supplemented with N-acetylglucosamine (Sze et al., 2013). "
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