Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146641
Title: The SiaABC threonine phosphorylation pathway controls biofilm formation in response to carbon availability in Pseudomonas aeruginosa
Authors: Poh, Wee Han
Lin, Jianqing
Colley, Brendan
Müller, Nicolai
Goh, Boon Chong
Schleheck, David
El Sahili, Abbas
Marquardt, Andreas
Liang, Yang
Kjelleberg, Staffan
Lescar, Julien
Rice, Scott A.
Klebensberger, Janosch
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Poh, W. H., Lin, J., Colley, B., Müller, N., Goh, B. C., Schleheck, D., . . . Klebensberger, J. (2020). The SiaABC threonine phosphorylation pathway controls biofilm formation in response to carbon availability in Pseudomonas aeruginosa. PLoS One, 15(11), e0241019-. doi:https://doi.org/10.1371/journal.pone.0241019
Project: SGP-PROG3-023. 2017 
AcRFtier 1 grant RG154/14 
Journal: PloS One 
Abstract: The critical role of bacterial biofilms in chronic human infections calls for novel anti-biofilm strategies targeting the regulation of biofilm development. However, the regulation of biofilm development is very complex and can include multiple, highly interconnected signal transduction/response pathways, which are incompletely understood. We demonstrated previously that in the opportunistic, human pathogen P. aeruginosa, the PP2C-like protein phosphatase SiaA and the di-guanylate cyclase SiaD control the formation of macroscopic cellular aggregates, a type of suspended biofilms, in response to surfactant stress. In this study, we demonstrate that the SiaABC proteins represent a signal response pathway that functions through a partner switch mechanism to control biofilm formation. We also demonstrate that SiaABCD functionality is dependent on carbon substrate availability for a variety of substrates, and that upon carbon starvation, SiaB mutants show impaired dispersal, in particular with the primary fermentation product ethanol. This suggests that carbon availability is at least one of the key environmental cues integrated by the SiaABCD system. Further, our biochemical, physiological and crystallographic data reveals that the phosphatase SiaA and its kinase counterpart SiaB balance the phosphorylation status of their target protein SiaC at threonine 68 (T68). Crystallographic analysis of the SiaA-PP2C domain shows that SiaA is present as a dimer. Dynamic modelling of SiaA with SiaC suggested that SiaA interacts strongly with phosphorylated SiaC and dissociates rapidly upon dephosphorylation of SiaC. Further, we show that the known phosphatase inhibitor fumonisin inhibits SiaA mediated phosphatase activity in vitro. In conclusion, the present work improves our understanding of how P. aeuruginosa integrates specific environmental conditions, such as carbon availability and surfactant stress, to regulate cellular aggregation and biofilm formation. With the biochemical and structural characterization of SiaA, initial data on the catalytic inhibition of SiaA, and the interaction between SiaA and SiaC, our study identifies promising targets for the development of biofilm-interference drugs to combat infections of this aggressive opportunistic pathogen.
URI: https://hdl.handle.net/10356/146641
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0241019
Rights: © 2020 Poh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCELSE Journal Articles

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