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Population structure of rat-derived Pneumocystis carinii in Danish wild rats
R J Palmer1, O P Settnes, J Lodal
1Molecular Infectious Diseases Group, Department of Paediatrics, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Abstract:
The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. carinii DNA was detected in 47 of 51 wild rats and in 10 of 12 nonimmunosuppressed laboratory rats. Evidence for three novel formae speciales of rat-derived P. carinii was found, and these were provisionally named Pneumocystis carinii f. sp. rattus-secundi, Pneumocystis carinii f. sp. rattus-tertii, and Pneumocystis carinii f. sp. rattus-quarti. Our data suggest that low-level carriage of P. carinii in wild rats and nonimmunosuppressed laboratory rats is common and that wild rats are frequently coinfected with more than one forma specialis of P. carinii. We also examined the diversity in the internally transcribed spacer (ITS) regions of the nuclear rRNA operon of Pneumocystis carinii f. sp. carinii by using samples from wild rats and laboratory rats and spore trap samples. We report a lack of variation in the ITS1 and ITS2 regions that is consistent with an evolutionary bottleneck in the P. carinii f. sp. carinii population. This study shows that human- and rat-derived P. carinii organisms are very different, not only in genetic composition but also in population structure and natural history.
Insights
Naturally acquired Pneumocystis carinii is common in wild and lab rats, with evidence of novel subtypes. This study highlights significant differences between rat and human Pneumocystis carinii, questioning the rat model
Area of Science:
- * Comparative genomics and population genetics of Pneumocystis species.
- * Infectious disease modeling and zoonotic potential.
- * Microbial ecology and host-pathogen interactions.
Background:
- * The rat model is widely used for studying Pneumocystis carinii pneumonia (PCP), but significant differences exist between rat and human infections.
- * Understanding naturally acquired Pneumocystis carinii in rats is crucial for assessing the relevance of the rat model.
Purpose of the Study:
- * To investigate the prevalence and genetic diversity of naturally acquired Pneumocystis carinii in wild and laboratory rats.
- * To compare rat-derived Pneumocystis carinii with human-derived strains.
- * To evaluate the suitability of the rat model for human PCP research.
Main Methods:
- * Detection of Pneumocystis carinii DNA in wild and laboratory rat samples using molecular methods.
- * Identification and characterization of novel formae speciales of rat-derived Pneumocystis carinii.
- * Analysis of the internally transcribed spacer (ITS) regions of the nuclear rRNA operon for genetic diversity.
Main Results:
- * Pneumocystis carinii DNA was detected in a high proportion of wild (47/51) and laboratory (10/12) rats.
- * Three novel formae speciales of rat-derived Pneumocystis carinii were identified: f. sp. rattus-secundi, f. sp. rattus-tertii, and f. sp. rattus-quarti.
- * Low-level carriage and frequent coinfection with multiple formae speciales were observed in wild rats.
- * A lack of variation in ITS1 and ITS2 regions of Pneumocystis carinii f. sp. carinii suggests an evolutionary bottleneck.
Conclusions:
- * Naturally acquired Pneumocystis carinii infection is common in both wild and laboratory rats.
- * Rat-derived Pneumocystis carinii exhibits significant genetic and population-level differences compared to human-derived strains.
- * The findings question the direct applicability of the rat model for all aspects of human Pneumocystis carinii pneumonia research.