Insights into the molecular basis of c-di-GMP signalling in Pseudomonas aeruginosa

Abstract

The opportunistic human pathogen Pseudomonas aeruginosa can cause severe infections in immunocompromized people or cystic fibrosis (CF) patients. Because of its remarkable ability to invade the host and withstand the bacteriocidal effect of most conventional antibiotics, the infection caused by P. aeruginosa has become a major concern for human health. The switch from acute to chronic infection is governed by the second messenger bis-(3′-5′)-cyclic dimeric guanosine mono-phosphate (c-di-GMP) in P. aeruginosa, and c-di-GMP is now recognized to regulate many important biological processes in pathogenesis. The c-di-GMP signalling mechanisms in P. aeruginosa have been studied extensively in the past decade, revealing complicated c-di-GMP metabolism and signalling network. In this review, the underlying mechanisms of this signalling network will be discussed, mainly focussing on how environmental cues regulate c-di-GMP signalling, protein–protein interaction mediated functional regulation, heterogeneity of c-di-GMP and cross talk between c-di-GMP signalling and other signalling systems. Understanding the molecular mechanism underlying the complex c-di-GMP signalling network would be beneficial for developing therapeutic approaches and antibacterial agents to combat the threat from P. aeruginosa.

Keywords:

• Pseudomonas aeruginosa
• c-di-GMP signalling
• environmental cues
• protein–protein interaction
• heterogeneity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from China Postdoctoral Science Foundation [grant no. 2021M691431], the Natural Research Foundation of China [grant no. 31330002, 31972230], the Guangdong Natural Science Foundation for Distinguished Young Scholar [grant no. 2020B1515020003], the Guangdong Natural Science Foundation [2020A1515011534], the Guangdong Technological Innovation Strategy of Special Funds [grant no. 2018B020205003], the Key Projects of Guangzhou Science and Technology Plan [grant no. 201804020066], the Guangzhou Municipal Science and Technology Bureau [grant no. 201607020044], and the Start-up Grant [grant no.Y01416110] from Southern University of Science and Technology.