Genetic Recombination and<i>Cryptosporidium hominis</i>Virulent Subtype IbA10G2

Li, Na; Xiao, Lihua; Cama, Vitaliano; Ortega, Ynés R.; Gilman, Robert H.; Guo, Meijin; Feng, Yaoyu

doi:10.3201/eid1910.121361

Cited by 68 publications

(52 citation statements)

References 39 publications

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“…The gp60 locus appears to be the site of genetic recombination, as many MLST subtypes differed from each other only at gp60 and the neighboring CP47, adding support for the theory that genetic recombination is a driving force in the emergence of the gp60 IaA28R4 subtype. Genetic exchange within an overall clonal population of Cryptosporidium parvum has been reported in Italy recently (26), and genetic recombination has been identified as a driving force in the emergence of the virulent epidemic C. hominis gp60 subtype IbA10G2 and the C. parvum subtype IIaA15G2R1 (27,28). Comparative genomic studies are needed to confirm the role of genetic recombination in the evolution of hyperinfectious or virulent Cryptosporidium subtypes.…”

Section: Discussionmentioning

confidence: 99%

Multilocus Sequence Typing of an Emerging Cryptosporidium hominis Subtype in the United States

Feng

Tiao

et al. 2014

J Clin Microbiol

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The United States has experienced a substantial increase in the reported incidence of cryptosporidiosis since 2005. Accompanying this is the emergence of a new subtype of Cryptosporidium hominis based on variation at the 60-kDa glycoprotein (gp60) locus, IaA28R4, which has become a frequently identified subtype in both sporadic and outbreak-related cases. In this study, using multilocus sequence typing (MLST) at eight genetic loci, we characterized 62 specimens of IaA28R4 and 33 specimens of three other gp60 subtypes of C. hominis from four U.S. states with increased cryptosporidiosis incidences during the summer of 2008. Extensive genetic heterogeneity was seen within the gp60 subtype IaA28R4, but specimens from Ohio and southwestern states formed two distinct subpopulations, suggesting that there were at least two origins of IaA28R4 within the United States. Discordance in typing results was observed between gp60 and other genetic markers, especially DZ-HRGP, and this discordance was largely the result of genetic recombination within the gp60 subtype IaA28R4. The results of population genetic analyses supported the presence of two subpopulations of IaA28R4 and the occurrence of genetic recombination within this gp60 subtype. Thus, the IaA28R4 subtype at gp60 is likely a fitness marker for C. hominis, and genetic recombination is potentially a driving force in the emergence of the virulent IaA28R4 subtype in the United States. A rapid evolution of IaA28R4 was indicated by the observation of multiple MLST subtypes of IaA28R4 within two large outbreaks that lasted for extended periods and involved multiple swimming pools.

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Section: Discussionmentioning

confidence: 99%

Multilocus Sequence Typing of an Emerging Cryptosporidium hominis Subtype in the United States

Feng

Tiao

et al. 2014

J Clin Microbiol

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“…Some of these studies have shown a panmictic population structure with frequent recombination in C. parvum (Herges et al 2012;De Waele et al 2013), whereas others have demonstrated the existence of a flexible reproductive strategy (co-occurrence of panmictic, clonal or epidemic structure) in this species (Tanriverdi et al 2008;Drumo et al 2012). Similarly, some genetic studies conducted on C. hominis identified largely a clonal population structure (Mallon et al 2003;Gatei et al 2007;Li et al 2013;Feng et al 2014), whereas others showed the common occurrence of genetic recombination in C. hominis in developing countries (Widmer and Sullivan, 2012). In areas with an overall clonal population structure of C. hominis, genetic recombination has been shown to be a driving force for the emergence of virulent subtypes such as IbA10G2 and IaA28R4 Feng et al 2014).…”

Section: Multilocus Typing and Population Geneticsmentioning

confidence: 99%

Cryptosporidiumspecies in humans and animals: current understanding and research needs

2014

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S U M M A R YCryptosporidium is increasingly recognized as one of the major causes of moderate to severe diarrhoea in developing countries. With treatment options limited, control relies on knowledge of the biology and transmission of the members of the genus responsible for disease. Currently, 26 species are recognized as valid on the basis of morphological, biological and molecular data. Of the nearly 20 Cryptosporidium species and genotypes that have been reported in humans, Cryptosporidium hominis and Cryptosporidium parvum are responsible for the majority of infections. Livestock, particularly cattle, are one of the most important reservoirs of zoonotic infections. Domesticated and wild animals can each be infected with several Cryptosporidium species or genotypes that have only a narrow host range and therefore have no major public health significance. Recent advances in next-generation sequencing techniques will significantly improve our understanding of the taxonomy and transmission of Cryptosporidium species, and the investigation of outbreaks and monitoring of emerging and virulent subtypes. Important research gaps remain including a lack of subtyping tools for many Cryptosporidium species of public and veterinary health importance, and poor understanding of the genetic determinants of host specificity of Cryptosporidium species and impact of climate change on the transmission of Cryptosporidium.

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“…are often further genotyped into subtypes using sequence analysis of the hypervariable 60-kDa glycoprotein (gp60) gene (3). Within C. hominis, the IbA10G2 subtype has been commonly associated with major outbreaks in industrialized nations (4)(5)(6) and has recently been identified as the genotype most likely to have undergone genetic recombination (7). Some studies suggest that such diversity may be linked to the polymorphic nature of telomeric regions (8,9).…”

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Genomic Variation in IbA10G2 and Other Patient-Derived Cryptosporidium hominis Subtypes

et al. 2017

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In order to improve genotyping and epidemiological analysis of Cryptosporidium spp., genomic data need to be generated directly from a broad range of clinical specimens. Utilizing a robust method that we developed for the purification and generation of amplified target DNA, we present its application for the successful isolation and whole-genome sequencing of 14 different Cryptosporidium hominis patient specimens. Six isolates of subtype IbA10G2 were analyzed together with a single representative each of 8 other subtypes: IaA20R3, IaA23R3, IbA9G3, IbA13G3, IdA14, IeA11G3T3, IfA12G1, and IkA18G1. Parasite burden was measured over a range of more than 2 orders of magnitude for all samples, while the genomes were sequenced to mean depths of between 17ϫ and 490ϫ coverage. Sequence homologybased functional annotation identified several genes of interest, including the gene encoding Cryptosporidium oocyst wall protein 9 (COWP9), which presented a predicted loss-of-function mutation in all the sequence subtypes, except for that seen with IbA10G2, which has a sequence identical to the Cryptosporidium parvum reference Iowa II sequence. Furthermore, phylogenetic analysis showed that all the IbA10G2 genomes form a monophyletic clade in the C. hominis tree as expected and yet display some heterogeneity within the IbA10G2 subtype. The current report validates the aforementioned method for isolating and sequencing Cryptosporidium directly from clinical stool samples. In addition, the analysis demonstrates the potential in mining data generated from sequencing multiple whole genomes of Cryptosporidium from human fecal samples, while alluding to the potential for a higher degree of genotyping within Cryptosporidium epidemiology.

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Genetic Recombination andCryptosporidium hominisVirulent Subtype IbA10G2

Cited by 68 publications

References 39 publications

Multilocus Sequence Typing of an Emerging Cryptosporidium hominis Subtype in the United States

Multilocus Sequence Typing of an Emerging Cryptosporidium hominis Subtype in the United States

Cryptosporidiumspecies in humans and animals: current understanding and research needs

Genomic Variation in IbA10G2 and Other Patient-Derived Cryptosporidium hominis Subtypes

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