Author : Mark Russell Liles
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (563 download)
Book Synopsis Type II Secretion of Virulence Factors and Iron Acquisition Mechanisms of Legionella Pneumophila by : Mark Russell Liles
Download or read book Type II Secretion of Virulence Factors and Iron Acquisition Mechanisms of Legionella Pneumophila written by Mark Russell Liles and published by . This book was released on 1998 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Survival and growth within the intracellular environment of an alveolar macrophage requires Legionella pneumophila to subvert the normal phagocytic pathway and acquire limiting nutrients, such as iron. Many pathogens excrete siderophores to chelate iron from host proteins. Biochemical investigations revealed that L. pneumophila supernatants contain multiple iron-binding molecules: the melanin homogentisic acid, the media component cysteine, and an unidentified low molecular weight molecule produced only in some strains of L. pneumophila. To identify iron uptake mechanisms by a genetic approach, transposon-generated mutants were screened for resistance to the iron-activated drug streptonigrin. While sequencing the L. pneumophila DNA downstream of the transposon in the mutant NU218, genes were discovered whose predicted proteins have strong homology to PilB, PilC, and PilD of Pseudomonas aeruginosa, proteins all required for type IV pilus biogenesis. Northern blot analysis demonstrated that the L. pneumophila pilBCD genes are expressed as an operon, and that pilBCD expression is greater at 30$\sp\circ$C than at 37$\sp\circ$C. This temperature-regulated pilBCD expression was correlated with an increase in piliation at 30$\sp\circ$C. Other investigators recently discovered the L. pneumophila type IV pilin subunit (PilE$\rm\sb{L}),$ and found that a $pilE\sb{L}$ mutant lacks type IV pili, but is fully competent for intracellular replication. Since PilD, the prepilin peptidase, is also required for type II protein secretion in other gram-negative bacteria, a pilD mutant was constructed to establish whether L. pneumophila exports proteins through a type II apparatus and whether this process contributes to pathogenesis. The pilD mutant exhibits a unique colony morphology, lacks type IV pili, and is impaired in replication within cultured human macrophages and amoebae. Additionally, the pilD mutant does not cause respiratory distress, high fever, weight loss, or death in guinea pigs, and is rapidly cleared from the lungs of infected animals. From these data it can be concluded that L. pneumophila has a type II secretion system, and that one or more proteins exported via this pathway are important for the virulence of L. pneumophila.
