The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1

Cai, Yu-Ming1; Yu, Kai-Wei2; Liu, Ji-Hong2,3; Cai, Zhao2; Zhou, Zun-Hao2; Liu, Yang3; Wang, Tian-Fu1; Yang, Liang2,4

2022-05-01

10.1128/aem.00039-22

APPLIED AND ENVIRONMENTAL MICROBIOLOGY   影响因子和分区

0099-2240

1098-5336

["The c-di-GMP signaling pathways in P. aeruginosa are highly organized and well coordinated, with different diguanylate cyclases and phosphodiesterases playing distinct roles in a complex network. Understanding the function of each enzyme and the underlying regulatory mechanisms not only is crucial for revealing how bacteria decide the transition between motile and sessile lifestyles, but also greatly facilitates the development of new antibiofilm strategies.","In Pseudomonas aeruginosa PAO1, 41 genes encode proteins predicted to be involved in the production or degradation of c-di-GMP, a ubiquitous secondary messenger that regulates a variety of physiological behaviors closely related to biofilm and aggregate formation. Despite extensive effort, the entire picture of this important signaling network is still unclear, with one-third of these proteins remaining uncharacterized. Here, we show that the deletion of pipA, which produces a protein containing two PAS domains upstream of a GGDEF-EAL tandem, significantly increased the intracellular c-di-GMP level and promoted the formation of aggregates both on surfaces and in planktonic cultures. However, this regulatory effect was not contributed by either of the two classic pathways modulating biofilm formation, exopolysaccharide (EPS) overproduction or motility inhibition. Transcriptome sequencing (RNA-Seq) data revealed that the expression levels of 361 genes were significantly altered in a Delta pipA mutant strain compared to the wild type (WT), indicating the critical role of PipA in PAO1. The most remarkably downregulated genes were located on the Pf4 bacteriophage gene cluster, which corresponded to a 2-log reduction in the Pf4 phage production in the Delta pipA mutant. The sizes of aggregates in Delta pipA cultures were affected by exogenously added Pf4 phage in a concentration-dependent manner, suggesting the quantity of phage plays a part in regulating the formation of aggregates. Further analysis demonstrated that PipA is highly conserved across 83 P. aeruginosa strains. Our work therefore for the first time showed that a c-di-GMP phosphodiesterase can regulate bacteriophage production and provided new insights into the relationship between bacteriophage and bacterial aggregation. IMPORTANCE The c-di-GMP signaling pathways in P. aeruginosa are highly organized and well coordinated, with different diguanylate cyclases and phosphodiesterases playing distinct roles in a complex network. Understanding the function of each enzyme and the underlying regulatory mechanisms not only is crucial for revealing how bacteria decide the transition between motile and sessile lifestyles, but also greatly facilitates the development of new antibiofilm strategies. This work identified bacteriophage production as a novel phenotypic output controlled transcriptionally by a phosphodiesterase, PipA. Further analysis suggested that the quantity of phage may be important in regulating autoaggregation, as either a lack of phage or overproduction was associated with higher levels of aggregation. Our study therefore extended the scope of c-di-GMP-controlled phenotypes and discovered a potential signaling circuit that can be target for biofilm treatment."]

Pseudomonas aeruginosa aggregation cyclic-di-GMP phosphodiesterase bacteriophage

SCI ; EI

英语

通讯

Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020003] ; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology[ZDSYS20200811144002008] ; Shenzhen Science and Technology Program[KQTD20200909113758004]

Biotechnology & Applied Microbiology ; Microbiology

Biotechnology & Applied Microbiology ; Microbiology

WOS:000806904600002

AMER SOC MICROBIOLOGY

20222612303395

Aggregates ; Bacteria ; Bacteriophages ; Biofilms ; C (programming language) ; Complex networks ; Genes ; Signal transduction ; Signaling

Highway Engineering:406 ; Concrete Reinforcements:412.2 ; Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Biomaterials (including synthetics):462.5 ; Computer Systems and Equipment:722 ; Computer Programming Languages:723.1.1 ; Organic Compounds:804.1

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Hlth Sci Ctr, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol Hosp, Med Res Ctr, Shenzhen, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen, Peoples R China

Cai, Yu-Ming,Yu, Kai-Wei,Liu, Ji-Hong,et al. The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1[J]. APPLIED AND ENVIRONMENTAL MICROBIOLOGY,2022,88.

Cai, Yu-Ming.,Yu, Kai-Wei.,Liu, Ji-Hong.,Cai, Zhao.,Zhou, Zun-Hao.,...&Yang, Liang.(2022).The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1.APPLIED AND ENVIRONMENTAL MICROBIOLOGY,88.

Cai, Yu-Ming,et al."The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1".APPLIED AND ENVIRONMENTAL MICROBIOLOGY 88(2022).