Genetic Variation in <i>Pneumocystis carinii</i> Isolates from Different Geographic Regions: Implications for Transmission

Beard, Charles B.; Carter, J. L.; Keely, Scott P.; Huang, Laurence; Pieniążek, Norman J.; Moura, Iaci N. S.; Roberts, Jerry; Hightower, Allen W.; Bens, M. S.; Freeman, A. R.; Lee, S.; Stringer, James R.; Duchin, Jeffrey S.; Rı́o, Carlos del; Rimland, David; Baughman, Robert P.; Levy, Deborah A.; Dietz, Vance; Simon, Philipp W.; Navin, Thomas R.

doi:10.3201/eid0603.000306

Cited by 217 publications

(165 citation statements)

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“…hominis) on the basis of the DNA sequence variations at a number of different genetic loci (2,26) including the internal transcribed spacers (ITSs) of the nuclear rRNA genes (7,13,15). Some of the more recent epidemiologic and clinical applications of molecular biology-based typing techniques have included studies on geographic variations and transmission modes (2), analysis of the potential emergence of antimicrobial resistance (8,16,18), and analysis of a potential linkage of genotype with disease severity (17).…”

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confidence: 99%

Genetic Diversity of Pneumocystis carinii f. sp. hominis Based on Variations in Nucleotide Sequences of Internal Transcribed Spacers of rRNA Genes

Nimri¹,

Moura²,

Huang

et al. 2002

J Clin Microbiol

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A variety of genes have been used to type Pneumocystis carinii. In the present study, nucleotide sequence variations in the ITS1 and ITS2 internal transcribed spacer (ITS) regions of the rRNA genes were used to type Pneumocystis carinii f. sp. hominis DNA obtained from the lungs of 60 human immunodeficiency virus-infected individuals. These regions were amplified by PCR, cloned, and sequenced. Multibase polymorphisms were identified among samples. Several new genotypes are reported on the basis of the nucleotide sequence variations at previously unreported positions of both the ITS1 and the ITS2 regions. Twelve new ITS1 sequences were observed, in addition to the nine sequence types reported previously. The most common was type E, which was observed in 60.5% of the samples. The sequence variations in the ITS1 region were mainly located at positions 5, 12, 23, 24, 45, 53, and 54. Sixteen new ITS2 types were also identified, in addition to the 13 types reported previously. The most common was type g (26.6%). The sequences of the ITS2 regions in most specimens were different from the previously published sequence at bases 120 and 166 through 183. The most common variations observed were deletions at positions 177 through 183. The presence of more than one sequence type in some patients (60%) suggested the occurrence of coinfection with multiple P. carinii strains. The genetic polymorphism observed demonstrates the degree of diversity of Pneumocystis strains that infect humans. Furthermore, the high degree of polymorphism suggests that these genes are evolving faster than other genes. Consequently, the sequence information derived is useful for purposes such as examination of the potential of person-to-person transmission and recurrent infections but perhaps not for other genotyping applications that rely on more stable genetic loci.Pneumocystis carinii is an opportunistic pathogen that causes potentially fatal pneumonia in immunocompromised or immunosuppressed patients. Despite the decrease in the incidence of the disease in human immunodeficiency virus HIV-infected patients (3), P. carinii pneumonia (PCP) continues to be a common AIDS-defining illness associated with significant mortality in both adults (8%) (3) and children (30%) (19).Although recent research has clarified our understanding of certain biological aspects of the organism, no standard method for the typing of P. carinii has emerged. Pure isolates of the organism are difficult to obtain in large amounts due to the lack of a standardized method of in vitro cultivation of humanderived P. carinii. Standard methods of typing have similarly been slow to develop (24).Despite evidence of genetic variations among human P. carinii isolates (12,20), the degree of diversity among strains that infect humans still lacks clarification. The existence of multiple strains of P. carinii that infect humans was first demonstrated by examination of the restriction fragment length polymorphisms (RFLPs) of P. carinii genomes from three patients (21). However, RFLP analyses...

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confidence: 99%

Genetic Diversity of Pneumocystis carinii f. sp. hominis Based on Variations in Nucleotide Sequences of Internal Transcribed Spacers of rRNA Genes

Nimri¹,

Moura²,

Huang

et al. 2002

J Clin Microbiol

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“…Drugs affecting genes in the essential eukaryotic core are likely to be broad spectrum in the fungal kingdom, for which there are few effective therapies (Georgopapadakou and Walsh 1994;Kaneshiro et al 2000). All known drug targets for Pneumocystis are associated with sterol metabolism, and resistance is already reported (Beard et al 2000) for the two major drugs for Pneumocystis pneumonia. Candidates for drug screening would include those genes in the core with no human homologs.…”

Section: Resultsmentioning

confidence: 99%

Essential Eukaryotic Core

Strobel

Arnold

2004

Evolution

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Abstract. The AIDs-related fungal pathogen Pneumocystis carinii is unusual in having a remarkably compact genome of 7.7 megabase pairs (mbp) whose small size presents the opportunity to identify the essential eukaryotic core of genes. The essential eukaryotic core is defined to be a collection of essential genes shared by all eukaryotes. Sequencing the 3Ј ends of more than 5500 cDNAs from P. carinii allowed us to identify about 200 genes shared with its nearest known but distant relative, Schizosaccharomyces pombe and also Saccharomyces cerevisiae, and with homologs known to be essential in S. pombe or S. cerevisae. As the cDNA library contains about one half of the P. carinii genes, the size of the essential eukaryotic core (ϳ400) is slightly larger than the prokaryotic core (265-350) being identified by studies of the bacterial pathogen Mycoplasma genitalium. The collection of genes in the essential eukaryotic core may prove useful in identifying new broad spectrum antifungal drug targets. The minimal gene complement of 256 genes essential to a bacterium, Mycoplasma genitalium with its about 700 kbp genome (one of the smallest), was recently identified by insertional mutagenesis (Hutchison et al. 1999). The question is whether or not there is a counterpart to Mycoplasma among eukaryotes that could be exploited to identify the minimal complement of genes shared by most eukaryotes and necessary to build a eukaryotic system, i.e., the essential eukaryotic core (Bennett and Arnold 2001). Pneumocystis, the major AIDs-related pathogen, is unusual in its biology in several respects, and having a list of its essential genes would be useful in selecting new drug targets (Cushion 1998). It has a compact genome of 7.7 mbp (Cushion et al. 1993) and no close relatives outside the genus to highlight shared features with other fungi (Cushion 1998). Extensive sequence of this genome is accumulating as part of the Pneumocystis Genome project (Xu et al. 2003). The sequence of Pneumocystis carinii can be compared with several nearly fully sequenced fungal genomes (Goffeau et al. 1996;Galagan et al. 2003). Two of these relatives of P. carinii, Schizosaccharomyces pombe and S. cerevisiae, have extensive data identifying their essential fungal genes (Winzeler et al. 1999). In this report we infer the essential eukaryotic core by utilizing the small genome size of P. carinii, its isolated phylogenetic position as a basal ascomycete (Edman et al. 1988) and the partial sequences of about one half of its genes having homologs to essential genes in S. pombe or S. cerevisiae. MATERIALS AND METHODSBecause P. carinii is uncultivable, cosmid and cDNA libraries were derived from the karyotype of P. carinii form 1, extracted from the lungs of immunologically suppressed rats during fulminate infection (Xu et al. 2003). Library construction from this karyotype is detailed in Smulian et al. (2001) and at http://pneumocystis.uc.edu. The cDNA library used in this study is in the vector pSK11, and the entire cDNA library is available from the Ameri...

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“…By examining patients who have suffered from pneumocystosis several times, different genetic types of P. jirovecii were isolated at subsequent stages of the disease (Keely et al 1995). Furthermore, it has been noted that the genetic pattern of Pneumocystis isolated from infected people is not similar to the pattern characteristic for isolates collected at their place of birth, but is more often in accordance with the pattern characteristic for the place in which the person resided at the time of collection of the specimen (Beard et al 2000).…”

Section: Introductionmentioning

confidence: 90%

The occurrence of Pneumocystis jirovecii in people from three different age groups of Warsaw (Poland) community

Gołąb

Sadkowska-Todys

Szkoda

et al. 2008

Acta Parasitologica

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The three age groups of people from Warsaw: children, young adults and elderly people were examined for the prevalence of infection with Pneumocystis jirovecii. Nested PCR was used to amplify fragment of mitochondrial large subunit rRNA of the fungus in samples of oropharyngeal swabs. Nineteen (12.8%) of the 148 examined samples were positive for DNA of P. jirovecii. The samples collected from children were more often positive than the samples from young adults (p = 0.003) or from both groups of adults (p = 0.0029). Moreover, among adults (n = 99) proportion of infected women (n = 6; 12.5%) was significantly higher than men (n = 1; 2%). Results of the research confirm the high prevalence of Pneumocystis infection in children and indirectly point out to children as a possible source of infection for older people.

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Genetic Variation in Pneumocystis carinii Isolates from Different Geographic Regions: Implications for Transmission

Cited by 217 publications

References 41 publications

Genetic Diversity of Pneumocystis carinii f. sp. hominis Based on Variations in Nucleotide Sequences of Internal Transcribed Spacers of rRNA Genes

Genetic Diversity of Pneumocystis carinii f. sp. hominis Based on Variations in Nucleotide Sequences of Internal Transcribed Spacers of rRNA Genes

Essential Eukaryotic Core

The occurrence of Pneumocystis jirovecii in people from three different age groups of Warsaw (Poland) community

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