Expression, cellular localization and interactions of the Pseudomonas aeruginosa diguanilate cyclase DgcP

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes infections in immunocompromised individuals, such as burn victims and cystic fibrosis patients. The World Health Organization classified carbapenem-resistant P. aeruginosa as one of the major threats towards infection control, urging the discovery of new antimicrobials. P. aeruginosa colonization of the host depends on a set of virulence factors that increases its adaptation, such as the type IV pili (T4P), required for attachment to surfaces and twitching motility related to the colonization of the host in chronic infections. The bis-(3',5')-cyclic di-guanosine monophosphate (c-di-GMP) is an important second messenger related with the decision between the biofilm and planktonic lifestyles which correspond to chronic and acute infections, respectively. It interacts with proteins involved in biofilm formation, motility, virulence and other processes. Some c-di-GMP- related proteins show distinct cellular localization and may interfere with local pools of this messenger upon external or internal stimuli, signaling for cellular or behavioral differentiation. DgcP is a polar localized diguanylate cyclase with its activity and localization dependent on the inner membrane protein FimV, required for T4P assembly. By increasing the c-di-GMP levels, DgcP decreases the flagellum driven motility and increases the biofilm formation by P. aeruginosa. However, it is not known how DgcP expression is regulated and whether it plays a role in polar localized signaling systems. Therefore, understanding the role of DgcP in the cellular differentiation that leads to the biofilm lifestyle is important, as this protein itself or the pathways where it belongs may represent a target for fighting P. aeruginosa infections. (AU)