Affiliation:
1. Center for Medical Mycology, Mycology Reference Laboratory, University Hospitals of Cleveland, and Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106-5028
Abstract
SUMMARY
Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Microbiology (medical),Public Health, Environmental and Occupational Health,General Immunology and Microbiology,Epidemiology
Reference231 articles.
1. Purification of a protein toxin from Corynebacterium ulcerans.;Abrehem K.;J. Med. Microbiol.,1980
2. Torulopsis glabrata infections in patients with cancer: increasing incidence and relationship to colonization.;Aisner J.;Am. J. Med.,1976
3. Cell membranes and cytolytic bacterial toxins;Alouf J. E.;The specificity and action of animal, bacterial and plant toxins. Receptors and recognition, series B,1977
4. Ansell
G. B.
Hawthorne
J. N.
Catabolism
Phospholipids.
Ansell
G. B.
Hawthorne
J. N.
1964
152
174
Elsevier Publishing Co.
Amsterdam The Netherlands
5. Avigad
G.
Microbial phospholipases
Mechanisms in bacterial toxinology.
Bernheimer
A. W.
1976
99
167
John Wiley & Sons Inc.
New York N.Y
Cited by
283 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献