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Infection and Immunity, January 2003, p. 47-60, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.47-60.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Diversity at the Locus Associated with Transcription of a Variable Surface Antigen of Pneumocystis carinii as an Index of Population Structure and Dynamics in Infected Rats

Scott P. Keely,1 Melanie T. Cushion,2 and James R. Stringer1*

Department of Molecular Genetics, Biochemistry and Microbiology,1 Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-05242

Received 13 June 2002/ Returned for modification 6 August 2002/ Accepted 10 October 2002

Pneumocystis carinii expresses a surface glycoprotein called MSG. Different isoforms of MSG are encoded by a gene family spread over at least 15 telomeric sites. Only one locus, called UCS, supports the production of MSG mRNA. Previous studies showed that P. carinii populations from individual rats exhibited high degrees of diversity with respect to the MSG genes attached to the UCS locus. This diversity could have been generated primarily in the rats studied. Alternatively, the rats may have been infected by P. carinii organisms that were already different at the UCS locus. To investigate this issue, we examined the UCS locus in P. carinii from rats that had been exposed to few of the microbes at a specified time, which produced a bottleneck in the microbial population. Some of the rats with bottlenecks produced P. carinii populations in which a single MSG sequence resided at the UCS locus in 80 to 90% of the organisms, showing that P. carinii can proliferate within a rat without generating the very high levels of UCS diversity previously seen. From the degree of diversity observed in the bottlenecked populations, the maximum rate of switching appeared to be 0.01 event per generation. These data also suggest that the infectious dose is as low as one organism, that rats that share a cage readily infect each other, and that the doubling time of P. carinii in vivo is ~3 days. In addition, we found that inoculation with 107 P. carinii organisms from a population highly heterogeneous at the UCS locus reproduced this heterogeneity. By contrast, shifts in population structure occurred in rats given 104 P. carinii organisms, suggesting that a small fraction of these proliferated.

* Corresponding author. Mailing address: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524. Phone: (513) 558-0097. Fax: (513) 558-8474. E-mail: stringjr{at}ucmail.uc.edu.

Editor: J. M. Mansfield

Infection and Immunity, January 2003, p. 47-60, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.47-60.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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