PMID- 26955366 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160309 LR - 20200929 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 7 DP - 2016 TI - SiaA/D Interconnects c-di-GMP and RsmA Signaling to Coordinate Cellular Aggregation of Pseudomonas aeruginosa in Response to Environmental Conditions. PG - 179 LID - 10.3389/fmicb.2016.00179 [doi] LID - 179 AB - Pseudomonas aeruginosa has emerged as an important opportunistic human pathogen that is often highly resistant to eradication strategies, mediated in part by the formation of multicellular aggregates. Cellular aggregates may occur attached to a surface (biofilm), at the air-liquid interface (pellicle), or as suspended aggregates. Compared to surface attached communities, knowledge about the regulatory processes involved in the formation of suspended cell aggregates is still limited. We have recently described the SiaA/D signal transduction module that regulates macroscopic cell aggregation during growth with, or in the presence of the surfactant SDS. Targets for SiaA/D mediated regulation include the Psl polysaccharide, the CdrAB two-partner secretion system and the CupA fimbriae. While the global regulators c-di-GMP and RsmA are known to inversely coordinate cell aggregation and regulate the expression of several adhesins, their potential impact on the expression of the cupA operon remains unknown. Here, we investigated the function of SiaA (a putative ser/thr phosphatase) and SiaD (a di-guanylate cyclase) in cupA1 expression using transcriptional reporter fusions and qRT-PCR. These studies revealed a novel interaction between the RsmA posttranscriptional regulatory system and SiaA/D mediated macroscopic aggregation. The RsmA/rsmY/Z system was found to affect macroscopic aggregate formation in the presence of surfactant by impacting the stability of the cupA1 mRNA transcript and we reveal that RsmA directly binds to the cupA1 leader sequence in vitro. We further identified that transcription of the RsmA antagonist rsmZ is controlled in a SiaA/D dependent manner during growth with SDS. Finally, we found that the siaD transcript is also under regulatory control of RsmA and that overproduction of RsmA or the deletion of siaD results in decreased cellular cyclic di-guanosine monophosphate (c-di-GMP) levels quantified by a transcriptional reporter, demonstrating that SiaA/D connects c-di-GMP and RsmA/rsmY/Z signaling to reciprocally regulate cell aggregation in response to environmental conditions. FAU - Colley, Brendan AU - Colley B AD - Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South Wales Sydney, NSW, Australia. FAU - Dederer, Verena AU - Dederer V AD - Institute of Technical Biochemistry, University of Stuttgart Stuttgart, Germany. FAU - Carnell, Michael AU - Carnell M AD - Biomedical Image Facility, Mark Wainwright Analytical Centre, University of New South Wales Sydney, NSW, Australia. FAU - Kjelleberg, Staffan AU - Kjelleberg S AD - Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia; Singapore Centre for Environmental Life Sciences Engineering and School of Biological Sciences, Nanyang Technological University, SingaporeSingapore. FAU - Rice, Scott A AU - Rice SA AD - Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia; Singapore Centre for Environmental Life Sciences Engineering and School of Biological Sciences, Nanyang Technological University, SingaporeSingapore. FAU - Klebensberger, Janosch AU - Klebensberger J AD - Institute of Technical Biochemistry, University of Stuttgart Stuttgart, Germany. LA - eng PT - Journal Article DEP - 20160226 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC4768041 OTO - NOTNLM OT - CupA fimbriae OT - Pseudomonas aeruginosa OT - RsmA OT - SiaA OT - SiaD OT - biofilm OT - c-di-GMP signaling OT - cellular aggregation EDAT- 2016/03/10 06:00 MHDA- 2016/03/10 06:01 PMCR- 2016/02/26 CRDT- 2016/03/09 06:00 PHST- 2015/11/26 00:00 [received] PHST- 2016/02/02 00:00 [accepted] PHST- 2016/03/09 06:00 [entrez] PHST- 2016/03/10 06:00 [pubmed] PHST- 2016/03/10 06:01 [medline] PHST- 2016/02/26 00:00 [pmc-release] AID - 10.3389/fmicb.2016.00179 [doi] PST - epublish SO - Front Microbiol. 2016 Feb 26;7:179. doi: 10.3389/fmicb.2016.00179. eCollection 2016.