Track topics on Twitter Track topics that are important to you
Pseudomonas aeruginosa secretes the virulence factor alkaline protease (AprA) to enhance its survival. AprA cleaves one of the key microbial recognition molecules, monomeric flagellin, and thereby diminishes Toll-like receptor 5 activation. In addition, AprA degrades host proteins such as complement proteins and cytokines. P. aeruginosa encodes a highly potent inhibitor of alkaline protease (AprI) that is solely located in the periplasm where it is presumed to protect periplasmic proteins against secreted AprA. We set out to study the enzyme-inhibitor interactions in more detail in order to provide a basis for future drug development. Structural and mutational studies reveal that the conserved N-terminal residues of AprI occupy the protease active site and are essential for inhibitory activity. We constructed peptides mimicking the N-terminus of AprI; however, these were incapable of inhibiting AprA-mediated flagellin cleavage. Furthermore, we expressed and purified AprI of P. aeruginosa and the homologous (37% sequence identity) AprI of Pseudomonas syringae, which remarkably show species specificity for their cognate protease. Exchange of the first five N-terminal residues between AprI of P. syringae and P. aeruginosa did not affect the observed specificity, whereas exchange of only six residues located at the AprI surface that contacts the protease did abolish specificity. These findings are elementary steps toward the design of molecules derived from the natural inhibitor of the virulence factor AprA and their use in therapeutic applications in Pseudomonas and other Gram-negative infections.
This article was published in the following journal.
Name: Journal of molecular biology
Pseudomonas aeruginosa is an opportunistic pathogen that can cause several acute and chronic infections in humans, and it has become an important cause of nosocomial infections and antibiotic resistan...
The mechanism by which low-dose macrolide therapy reduces exacerbations in non-CF bronchiectasis (NCFBE) is not known. Pseudomonas aeruginosa quorum sensing (QS) controls the expression of a range of ...
Pseudomonas aeruginosa is one of the major pathogens responsible for hospital-acquired infections, which harbor a wide array of virulence factors. The main aim of this study was to determine the frequ...
Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antim...
The gastrointestinal tract is not the common infection site of Pseudomonas aeruginosa. The role of P. aeruginosa as a causative agent for diarrhea in children without pre-existing disease is controver...
Pseudomonas aeruginosa (Pa) is the bacterium that causes one of the most consequential lung infections in people with CF. Many young children do not have Pa in their lungs but will become ...
Clinical Trial looking to Evaluate the Efficacy and Safety of MEDI3902 in Mechanically Ventilated Patients for the Prevention of Nosocomial Pneumonia Caused by Pseudomonas aeruginosa
The present study focuses on patients with Pseudomonas aeruginosa (PSA) sepsis. The aim of the present study is to find out whether the M1 (pro-inflammatory) or M2 (anti-inflammatory) phen...
This is an open-label, single arm (uncontrolled) study in subjects suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 (all visits) and who were pr...
Rates of DMBT1 (Glycoprotein like) in Sputum of CF Patients with or without may be different according to their Pseudomonas Aeruginosa chronic colonization status. The aim of this study is...
A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.
Antibiotic pigment produced by Pseudomonas aeruginosa.
Bacteriocins elaborated by mutant strains of Pseudomonas aeruginosa. They are protein or protein-lipopolysaccharide complexes lethal to other strains of the same or related species.
Viruses whose host is Pseudomonas. A frequently encountered Pseudomonas phage is BACTERIOPHAGE PHI 6.
Reducing the SURFACE TENSION at a liquid/solid interface by the application of an electric current across the interface thereby enhancing the WETTABILITY of the surface.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...