Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.
Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzoot...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-06-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3128128?pdf=render |
| _version_ | 1819030927261564928 |
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| author | Ming He Zhiming Ouyang Bryan Troxell Haijun Xu Akira Moh Joseph Piesman Michael V Norgard Mark Gomelsky X Frank Yang |
| author_facet | Ming He Zhiming Ouyang Bryan Troxell Haijun Xu Akira Moh Joseph Piesman Michael V Norgard Mark Gomelsky X Frank Yang |
| author_sort | Ming He |
| collection | DOAJ |
| description | Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host. |
| first_indexed | 2024-12-21T06:37:56Z |
| format | Article |
| id | doaj.art-243f5e1744d24c00916f447f6a4d6dd3 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T06:37:56Z |
| publishDate | 2011-06-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj.art-243f5e1744d24c00916f447f6a4d6dd32022-12-21T19:12:49ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-06-0176e100213310.1371/journal.ppat.1002133Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.Ming HeZhiming OuyangBryan TroxellHaijun XuAkira MohJoseph PiesmanMichael V NorgardMark GomelskyX Frank YangCyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.http://europepmc.org/articles/PMC3128128?pdf=render |
| spellingShingle | Ming He Zhiming Ouyang Bryan Troxell Haijun Xu Akira Moh Joseph Piesman Michael V Norgard Mark Gomelsky X Frank Yang Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. PLoS Pathogens |
| title | Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. |
| title_full | Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. |
| title_fullStr | Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. |
| title_full_unstemmed | Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. |
| title_short | Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks. |
| title_sort | cyclic di gmp is essential for the survival of the lyme disease spirochete in ticks |
| url | http://europepmc.org/articles/PMC3128128?pdf=render |
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