Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle.
Many bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP. Behavioral transitions result from the coordination of complex cellular processes such as motility, surface adherence or the production of virulence factors and toxins. While the regulatory mecha...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3764195?pdf=render |
| _version_ | 1819045566476189696 |
|---|---|
| author | Sören Abel Tabitha Bucher Micaël Nicollier Isabelle Hug Volkhard Kaever Pia Abel Zur Wiesch Urs Jenal |
| author_facet | Sören Abel Tabitha Bucher Micaël Nicollier Isabelle Hug Volkhard Kaever Pia Abel Zur Wiesch Urs Jenal |
| author_sort | Sören Abel |
| collection | DOAJ |
| description | Many bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP. Behavioral transitions result from the coordination of complex cellular processes such as motility, surface adherence or the production of virulence factors and toxins. While the regulatory mechanisms responsible for these processes have been elucidated in some cases, the global pleiotropic effects of c-di-GMP are poorly understood, primarily because c-di-GMP networks are inherently complex in most bacteria. Moreover, the quantitative relationships between cellular c-di-GMP levels and c-di-GMP dependent phenotypes are largely unknown. Here, we dissect the c-di-GMP network of Caulobacter crescentus to establish a global and quantitative view of c-di-GMP dependent processes in this organism. A genetic approach that gradually reduced the number of diguanylate cyclases identified novel c-di-GMP dependent cellular processes and unraveled c-di-GMP as an essential component of C. crescentus cell polarity and its bimodal life cycle. By varying cellular c-di-GMP concentrations, we determined dose response curves for individual c-di-GMP-dependent processes. Relating these values to c-di-GMP levels modeled for single cells progressing through the cell cycle sets a quantitative frame for the successive activation of c-di-GMP dependent processes during the C. crescentus life cycle. By reconstructing a simplified c-di-GMP network in a strain devoid of c-di-GMP we defined the minimal requirements for the oscillation of c-di-GMP levels during the C. crescentus cell cycle. Finally, we show that although all c-di-GMP dependent cellular processes were qualitatively restored by artificially adjusting c-di-GMP levels with a heterologous diguanylate cyclase, much higher levels of the second messenger are required under these conditions as compared to the contribution of homologous c-di-GMP metabolizing enzymes. These experiments suggest that a common c-di-GMP pool cannot fully explain spatiotemporal regulation by c-di-GMP in C. crescentus and that individual enzymes preferentially regulate specific phenotypes during the cell cycle. |
| first_indexed | 2024-12-21T10:30:37Z |
| format | Article |
| id | doaj.art-8898e52480304c4e84b07b9d39e90a34 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-21T10:30:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-8898e52480304c4e84b07b9d39e90a342022-12-21T19:07:13ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0199e100374410.1371/journal.pgen.1003744Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle.Sören AbelTabitha BucherMicaël NicollierIsabelle HugVolkhard KaeverPia Abel Zur WieschUrs JenalMany bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP. Behavioral transitions result from the coordination of complex cellular processes such as motility, surface adherence or the production of virulence factors and toxins. While the regulatory mechanisms responsible for these processes have been elucidated in some cases, the global pleiotropic effects of c-di-GMP are poorly understood, primarily because c-di-GMP networks are inherently complex in most bacteria. Moreover, the quantitative relationships between cellular c-di-GMP levels and c-di-GMP dependent phenotypes are largely unknown. Here, we dissect the c-di-GMP network of Caulobacter crescentus to establish a global and quantitative view of c-di-GMP dependent processes in this organism. A genetic approach that gradually reduced the number of diguanylate cyclases identified novel c-di-GMP dependent cellular processes and unraveled c-di-GMP as an essential component of C. crescentus cell polarity and its bimodal life cycle. By varying cellular c-di-GMP concentrations, we determined dose response curves for individual c-di-GMP-dependent processes. Relating these values to c-di-GMP levels modeled for single cells progressing through the cell cycle sets a quantitative frame for the successive activation of c-di-GMP dependent processes during the C. crescentus life cycle. By reconstructing a simplified c-di-GMP network in a strain devoid of c-di-GMP we defined the minimal requirements for the oscillation of c-di-GMP levels during the C. crescentus cell cycle. Finally, we show that although all c-di-GMP dependent cellular processes were qualitatively restored by artificially adjusting c-di-GMP levels with a heterologous diguanylate cyclase, much higher levels of the second messenger are required under these conditions as compared to the contribution of homologous c-di-GMP metabolizing enzymes. These experiments suggest that a common c-di-GMP pool cannot fully explain spatiotemporal regulation by c-di-GMP in C. crescentus and that individual enzymes preferentially regulate specific phenotypes during the cell cycle.http://europepmc.org/articles/PMC3764195?pdf=render |
| spellingShingle | Sören Abel Tabitha Bucher Micaël Nicollier Isabelle Hug Volkhard Kaever Pia Abel Zur Wiesch Urs Jenal Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. PLoS Genetics |
| title | Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. |
| title_full | Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. |
| title_fullStr | Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. |
| title_full_unstemmed | Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. |
| title_short | Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. |
| title_sort | bi modal distribution of the second messenger c di gmp controls cell fate and asymmetry during the caulobacter cell cycle |
| url | http://europepmc.org/articles/PMC3764195?pdf=render |
| work_keys_str_mv | AT sorenabel bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT tabithabucher bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT micaelnicollier bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT isabellehug bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT volkhardkaever bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT piaabelzurwiesch bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle AT ursjenal bimodaldistributionofthesecondmessengercdigmpcontrolscellfateandasymmetryduringthecaulobactercellcycle |