The molecular basis of Leptospiral Pathogenesis

Gerald L Murray

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

32 Citations (Scopus)

Abstract

The mechanisms of disease pathogenesis in leptospirosis are poorly defined. Recent developments in the application of genetic tools in the study of Leptospira have advanced our understanding by allowing the assessment of mutants in animal models. As a result, a small number of essential virulence factors have been identified, though most do not have a clearly defined function. Significant advances have also been made in the in vitro characterization of leptospiral interaction with host structures, including extracellular matrix proteins (such as laminin, elastin, fibronectin, collagens), proteins related to hemostasis (fibrinogen, plasmin), and soluble mediators of complement resistance (factor H, C4b-binding protein), although none of these in vitro findings has been translated to the host animal. Binding to host structures may permit colonization of the host, prevention of blood clotting may contribute to hemorrhage, while interaction with complement resistance mediators may contribute to survival in serum. While not a classical intracellular pathogen, the interaction of leptospires and phagocytic cells appears complex, with bacteria surviving uptake and promoting apoptosis; mutants relating to these processes (such as cell invasion and oxidative stress resistance) are attenuated in vivo. Another feature of leptospiral biology is the high degree of functional redundancy and the surprising lack of attenuation of mutants in what appear to be certain virulence factors, such as LipL32 and LigB. While many advances have been made, there remains a lack of understanding of how Leptospira causes tissue pathology. It is likely that leptospires have many novel pathogenesis mechanisms that are yet to be identified.
Original languageEnglish
Title of host publicationLeptospira and Leptospirosis
EditorsBen Adler
Place of PublicationGermany
PublisherSpringer
Pages139-188
Number of pages50
Edition1st
ISBN (Electronic)978-3-662-45059-8
ISBN (Print)978-3-662-45058-1
DOIs
Publication statusPublished - 2015

Publication series

NameCurrent Topics in Microbiology
Volume387
ISSN (Print)0070-217X
ISSN (Electronic)2196-9965

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