Targeting mechanisms of Pseudomonas aeruginosa pathogenesis

 

TITLE

Targeting mechanisms of Pseudomonas aeruginosa pathogenesis

STAFF

A. Pesaresi*, D.Lamba
[*] Research Associate

KEYWORDS

Pseudomonas aeruginosa , cystic fibrosis, carboxylesterase, a/b hydrolase

COLLABORATIONS
International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Facultè de Mèdicine, Universitè Laval, Quèbec (Canada)
DESCRIPTION

Pseudomonas aeruginosa (PA) is a ubiquitous gram-negative bacterium that is capable of surviving in a broad range of natural environments, although it is mostly known for its role as an opportunistic pathogen . While PA is generally found in aerobic environments, it is able to thrive anoxically and, notably, to denitrify . It has also recently been shown that PA can form biofilms under microaerobic (i.e.,very low oxygen) conditions similar to those found in the lungs of cystic fibrosis (CF) patients . These features strongly contribute to the notable success of PA in chronically infecting the lungs of CF patients, nearly all of whom have lifelong PA infections starting at an early age. PA is also a serious pathogen in nosocomial infections and various acute infections in immuno-compromised patients such as severe burns and urinary tract infections. Part of the reason for this remarkable ecological success is thought to be the considerable metabolic versatility and flexibility of PA, which renders the study of metabolism of this life-threatening microbe crucial to the understanding of its pathogenicity and opportunistic nature. Adding to the problems of high incidence and infection severity, the resistance of PA to conventional antimicrobial treatment has increased over the past decade. It is crucial that new therapeutic options for PA infections be explored. Such new options may came from specifically targeting the pathogenic mechanisms of PA.
We have purified an intracellular putative carboxylesterase encoded by the open reading frame PA3859 of PA and elucidated its 3D crystal structure. With the ultimate aim of gaining deeper insights into the PA3859 in vivo function, the binding properties of the enzyme active site are currently exploited by enzymatic assay and automated docking simulation that should provide structural clues with respect to the physiological substrates. The ability of the PA3859 knock out mutant to compete with the wild type PA will also be exploited in a rat model of chronic lung infection a useful tool for CF studies.

Pesaresi A, Devescovi G, Lamba D, Venturi V, Degrassi G. Isolation, characterization, and heterologous expression of a carboxylesterase of Pseudomonas aeruginosa PAO1. Curr Microbiol (2005) 50, 102

Pesaresi A, Lamba D. Crystallization, X-ray diffraction analysis and phasing of carboxylesterase PA3859 from Pseudomonas aeruginosa. Biochim Biophys Acta (2005) 1752, 197

Pesaresi A, Lamba D. Insights into the fatty acid chain length specificity of the carboxylesterase PA3859 from Pseudomonas aeruginosa: combined structural, biochemical and computational study. Biochemie (2010) under revision.

CONTACTS

 

Doriano Lamba
Email : doriano.lambaATts.ic.cnr.it
Tel : +39-040-3758514

 

Last Updated (Tuesday, 21 December 2010 17:01)