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Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Infection and immunity (Impact Factor: 4.16). 06/2011; 79(8):3273-83. DOI: 10.1128/IAI.05153-11
Source: PubMed

ABSTRACT HD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria. Borrelia burgdorferi possesses a single set of c-di-GMP-metabolizing enzymes, including a putative HD-GYP domain protein, BB0374. Recently, we characterized the EAL domain phosphodiesterase PdeA. A mutation in pdeA resulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with a K(m) of 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing the pdeA pdeB double mutant, we demonstrate that no additional phosphodiesterases are present in B. burgdorferi. pdeB single mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing a pilZ pdeB double mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly in pdeB mutant cells, these cells exhibited a reduced ability to survive in Ixodes scapularis ticks. Consequently, those ticks were unable to transmit the infection to naïve mice. All of these phenotypes were restored when the mutant was complemented. Identification of this role of pdeB increases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle of B. burgdorferi.

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    • "RpfG from Xanthomonas campestris promotes synthesis of virulence factors and affects biofilm formation and motility (Ryan et al., 2010, 2012). The Borrelia burgdorferi PdeB controls motility and promotes virulence in ticks (Sultan et al., 2011). Two HD-GYP domain proteins from Pseudomonas aeruginosa control swarming motility and production of virulence factors (Ryan et al., 2009). "
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    • "Cyclic di-GMP signalling is not required for virulence of Y. pestis in a plague mouse model (Bobrov et al., 2011) and also the Lyme disease spirochaete Borrelia burgdorferi can successfully cause infection in mice without using its cyclic di-GMP signalling system (He et al., 2011). Even more, uncontrolled high cyclic di-GMP levels achieved by deletion of the single phosphodiesterase inhibit acute infection through the expression of extracellular biofilm matrix components (Bobrov et al., 2011; Sultan et al., 2011). On the other hand, biofilm formation, which is stimulated by cyclic di-GMP signalling, is a virulence factor in chronic infections (Tamayo et al., 2007). "
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