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All in a day's work for a fungi
The last word All in a day’s work for a fungi Bernard Dixon 130 Cornwall Road, Ruislip Manor, Middlesex HA4 6AW, UK
What is it that fits a fungus whose natural habitat is the soil, to be pathogenic in the very different environment of the human body? One answer, suggested by Arturo Casadevall and his colleagues in New York, is that fungal characteristics associated with virulence in mammals can be the same as those needed for survival inside soil amoebae There is an odd quirk of history here too. The new insight comes from work on an amoeba that was first reported by Italian microbiologist Aldo Castellani, author of the classic Microbes, Men and Monarchs (Gollancz, 1960). Not only that, the New York research is closely linked with the circumstances in which Castellani isolated the soil protozoon Acanthamoeba sp back in the late 1920s. The fungus concerned is Cryptococcus neoformans, which (as far as we know) causes infections only rarely in normal individuals but is responsible for life-threatening meningitis in immunocompromised patients. It is found in soil, often when contaminated with pigeon excreta, and human infection is thought to occur through the inhalation of dust containing the organism. C neoformans is a facultative intracellular pathogen, both in vivo and in vitro. Casadevall and co-workers at Columbia University and Abert Einstein College of Medicine wondered whether, like the bacterium Legionella pneumophila, it might multiply and persist inside amoebae just as it does within macrophages. Despite their very different locations, both of these types of cell normally phagocytose foreign organisms, which pass into their vacuoles where they are digested by lysosomal enzymes. Could it be that C neoformans, like L pneumophila, has evolved ways of resisting this process? So it proved, as reported in the Proceedings of the National Academy of Sciences (2001; 98: 15245–50). Using microscopy and other techniques, the New York team first established that the fungus was indeed phagocytosed by Acanthamoeba castellanii. But rather than being killed, the fungus replicated, killing its host.
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Moreover, the protozoon ingested C neoformans strains more avidly when they lacked a polysaccharide capsule. The capsule seems to protect the organism, both from phagocytosis by amoebae in the soil and from macrophages in the body. Immunofluorescence studies also revealed the presence of polysaccharide-containing vacuoles in the amoebae very like those seen in infected macrophages. These findings indicate that a strategy evolved to favour survival among grazing protozoa in the soil may also help C neoformans to overcome host defences and thereby cause human disease—especially in immunocompromised individuals. Complementary evidence came from work on specific virulence factors. Previous studies by Casadevall and his colleagues had shown that phospholipase is an importance virulence determinant for this fungus. A phospholipase mutant was considerably less virulent, both in vivo and in vitro, than strains capable of producing the enzyme. Now the New Yorkers have found that the same mutant is unable to grow in A castellanii. Taken together, this and other evidence leads the group to suggest an explanation of why C neoformans can infect many different species, not only of mammals but also birds. It spans this remarkable host range, they believe, because it subverts macrophage fungicidal activity using strategies originally selected for surviving interactions with amoebae and other natural predators. Recent years have seen a growing awareness of the role of environmental protozoa in harbouring bacteria such as L pneumophila and thereby maintaining and even enhancing their virulence. But this is the first example of such a phenomenon among fungi. One wonders just how many others remain to be discovered. And the historic connection with the work of Aldo Castellani? He it was who, in 1930, first isolated acanthamoeba—from an accidentally contaminated culture of cryptococci.
THE LANCET Infectious Diseases Vol 2 August 2002
http://infection.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
What is it that fits a fungus whose natural habitat is the soil, to be pathogenic in the very different environment of the human body? One answer, suggested by Arturo Casadevall and his colleagues in New York, is that fungal characteristics associated with virulence in mammals can be the same as those needed for survival inside soil amoebae There is an odd quirk of history here too. The new insight comes from work on an amoeba that was first reported by Italian microbiologist Aldo Castellani, author of the classic Microbes, Men and Monarchs (Gollancz, 1960). Not only that, the New York research is closely linked with the circumstances in which Castellani isolated the soil protozoon Acanthamoeba sp back in the late 1920s. The fungus concerned is Cryptococcus neoformans, which (as far as we know) causes infections only rarely in normal individuals but is responsible for life-threatening meningitis in immunocompromised patients. It is found in soil, often when contaminated with pigeon excreta, and human infection is thought to occur through the inhalation of dust containing the organism. C neoformans is a facultative intracellular pathogen, both in vivo and in vitro. Casadevall and co-workers at Columbia University and Abert Einstein College of Medicine wondered whether, like the bacterium Legionella pneumophila, it might multiply and persist inside amoebae just as it does within macrophages. Despite their very different locations, both of these types of cell normally phagocytose foreign organisms, which pass into their vacuoles where they are digested by lysosomal enzymes. Could it be that C neoformans, like L pneumophila, has evolved ways of resisting this process? So it proved, as reported in the Proceedings of the National Academy of Sciences (2001; 98: 15245–50). Using microscopy and other techniques, the New York team first established that the fungus was indeed phagocytosed by Acanthamoeba castellanii. But rather than being killed, the fungus replicated, killing its host.
508
Moreover, the protozoon ingested C neoformans strains more avidly when they lacked a polysaccharide capsule. The capsule seems to protect the organism, both from phagocytosis by amoebae in the soil and from macrophages in the body. Immunofluorescence studies also revealed the presence of polysaccharide-containing vacuoles in the amoebae very like those seen in infected macrophages. These findings indicate that a strategy evolved to favour survival among grazing protozoa in the soil may also help C neoformans to overcome host defences and thereby cause human disease—especially in immunocompromised individuals. Complementary evidence came from work on specific virulence factors. Previous studies by Casadevall and his colleagues had shown that phospholipase is an importance virulence determinant for this fungus. A phospholipase mutant was considerably less virulent, both in vivo and in vitro, than strains capable of producing the enzyme. Now the New Yorkers have found that the same mutant is unable to grow in A castellanii. Taken together, this and other evidence leads the group to suggest an explanation of why C neoformans can infect many different species, not only of mammals but also birds. It spans this remarkable host range, they believe, because it subverts macrophage fungicidal activity using strategies originally selected for surviving interactions with amoebae and other natural predators. Recent years have seen a growing awareness of the role of environmental protozoa in harbouring bacteria such as L pneumophila and thereby maintaining and even enhancing their virulence. But this is the first example of such a phenomenon among fungi. One wonders just how many others remain to be discovered. And the historic connection with the work of Aldo Castellani? He it was who, in 1930, first isolated acanthamoeba—from an accidentally contaminated culture of cryptococci.
THE LANCET Infectious Diseases Vol 2 August 2002
http://infection.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.