Genetics of Surface Antigen Expression inPneumocystis carinii

Abstract

This article reviews the molecular genetic data pertaining to the major surface glycoprotein (MSG) gene family of Pneumocystis carinii and its role in surface variation and compares this fungal system to antigenic variation systems in the protozoan Trypanosoma brucei and the bacteria Borrelia spp. PNEUMOCYSTIS CARINIIPneumocystis carinii is a fungus that can cause pneumonia in immunocompromised mammals (100, 174). While P. carinii was recognized nearly a century ago and has been a significant human pathogen since the beginning of the AIDS epidemic, this organism is not well understood. Much of the blame for the lack of basic information about this organism and its natural history can be placed on its failure to grow well in culture. Populations of the organism can be maintained in broth culture, but growth in culture has not been good enough to allow either production of large numbers or derivation of clonally derived stocks (95). Therefore, in vitro culture has been of limited utility for studying the genetics and biochemistry of P. carinii.By contrast, large numbers of organisms can be routinely obtained from laboratory animals. Most of what is known about P. carinii has been learned from studies with animals, and most of what is known about the surface antigen genes was determined from studies on organisms from laboratory rats. Reliance on rats as the source of P. carinii has had its advantages and disadvantages, which have shaped the course of research on antigenic variation. It is important, therefore, to preface this review with a brief description of the general features of rat models of P. carinii infection.The rat model of P. carinii pneumonia (Pcp) has its roots in studies that showed that P. carinii infections can be provoked by treating rats with chemical immunosuppressants (18,24,38,53). These infections appeared to be caused by growth of P. carinii that was present in the rats at the time of immunosuppression (reactivation of latent infections). Most, if not all, commercial rat colonies harbor P. carinii in a latent form, where it can persist for up to a year (103,162,178). It seems most plausible that P. carinii maintains itself in rat colonies via airborne transmission from older rats to neonates, and evidence for airborne transmission has been obtained in laboratory settings (53,55,176). However, other mechanisms of transmission from adults to neonates have not been excluded, and observations suggestive of transplacental transfer have been reported (17).Even though latent infections are common in laboratory rats, simply immunosuppressing rats does not always lead to the production of large numbers of organisms per animal. This observation led to the implementation of a protocol known as the natural transmission method. In this method, rats are bred in colonies known to harbor latent infections. Young animals in such colonies are immunosuppressed and housed in openair cages. Some or all of the immunosuppressed animals develop heavy infections. When new young animals from another source (such as a...

Ku Is Important for Telomere Maintenance, but Not for Differential Expression of Telomeric VSG Genes, in African Trypanosomes

“…Besides the trypanosome VSGs, which are transcribed only from telomeric loci in the distinct metacyclic and bloodstream populations and have a large subset of silent genes at minichromosomal telomeres, there are examples in protozoa (25,54), the fungus Pneumocystis (26), and even on linear plasmids in the bacterium Borrelia hermsii (55). These systems rely on the existence of a wide set of silent genes (or segments) and the expression of only one gene at a time.…”

Functional Differentiation of tbf1 Orthologues in Fission and Budding Yeasts

“…The subtelomeric regions harbor tandemly repeated copies of several gene families (1,30,31,53), including the abundantly expressed major surface glycoproteins (MSGs), which play an important role in the host-parasite interaction and the escape from host responses during lung infection (20,58). Only a single copy of approximately 100 or so MSG genes is expressed at any one time; telomeric recombination appears to mediate the switching of different antigenic variants into the unique subtelomeric locus from which expression takes place (29,56,57,60). Whether the integrity of P. carinii telomere ends is maintained through telomerase-based addition of repeats or entirely by recombination is still unclear.…”

Basic biology of Pneumocystis carinii: a mini review

“…These genes are localized at the ends, upstream of the subtelomeric and telomeric repeats of all chromosomes. Transcription is limited to a single gene each time and is involved in a process that resembles the antigenic variation that has been well characterized in Trypanosma brucei (Stringer & Keely 2001).…”