Time between Inoculations and Karyotype Forms of Pneumocystis carinii f. sp. carinii Influence Outcome of Experimental Coinfections in Rats

doi:10.1128/IAI.69.1.97-107.2001

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Infection and Immunity, January 2001, p. 97-107, Vol. 69, No. 1
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.1.97-107.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Time between Inoculations and Karyotype Forms of Pneumocystis carinii f. sp. carinii Influence Outcome of Experimental Coinfections in Rats

Melanie T. Cushion,¹^,²^,^* Sally Orr,¹^,² Scott P. Keely,³ and James R. Stringer³

Department of Internal Medicine, Division of Infectious Diseases,¹ and Department of Molecular Genetics, Biochemistry, and Microbiology,³ University of Cincinnati College of Medicine, and the Cincinnati VA Medical Center,² Cincinnati, Ohio

Received 11 April 2000/Returned for modification 4 July 2000/Accepted 27 September 2000

The prevalence of Pneumocystis carinii pneumonia (PCP) in humans caused by more than a single genotype has been reported torange from 10 to 67%, depending on the method used for detection(3, 19). Most coinfections were associated with primary ratherthan recurrent disease. To better understand the factors influencingthe development of coinfections, the time periods between inoculationsand the genotype of the infecting organisms were evaluated inthe chronically immunosuppressed-inoculated rat model of PCP.P. carinii f. sp. carinii infecting rats differentiated by karyotypicprofiles exhibit the same low level of genetic divergence manifestedby organisms infecting humans. P. carinii f. sp. carinii karyotypeforms 1, 2, and 6 were inoculated into immunosuppressed rats,individually and in dual combinations, spaced 0, 10, and 20 daysapart. Infections comprised of both organism forms resulted fromadmixtures inoculated at the same time. In contrast, coinfectionsdid not develop in most rats, where a 10- or 20-day gap was insertedbetween inoculations; only the first organism form inoculatedwas detected by pulsed-field gel electrophoresis in the resultantinfection. Organism burdens were reduced with combinations offorms 1 and 2 spaced 20 days apart but not in rats inoculatedwith forms 1 and 6. A role for the host response in the eliminationof the second population and in reduction of the organism burdenwas suggested by the lack of direct killing of forms 1 and 2 inan in vitro ATP assay, by reduction of the burden by autoclavedorganisms, and by the specific reactions of forms 1 and 2 butnot forms 1 and 6. These studies showed that the time betweeninoculations was critical in establishing coinfections and P.carinii f. sp. carinii karyotype profiles were associated withdifferences in biological responses. This model provides a usefulmethod for the study of P. carinii coinfections and their transmissioninhumans.

^* Corresponding author. Mailing address: University of Cincinnati College of Medicine, 231 Bethesda Ave., Cincinnati, OH 45267-0560.Phone: (513) 861-3100, ext. 4417. Fax: (513) 475-6415. E-mail:Melanie.Cushion{at}Uc.Edu.

Infection and Immunity, January 2001, p. 97-107, Vol. 69, No. 1
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.1.97-107.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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