Genetic Diversity of Cryptosporidium hominis in a Bangladeshi Community as Revealed by Whole-Genome Sequencing

Gilchrist, Carol A.; Cotton, James A.; Burkey, Cecelia; Arju, Tuhinur; Gilmartin, Allissia A.; Ye, Lin; Ahmed, Emtiaz; Steiner, Kevin L.; Alam, Masud; Ahmed, Shahnawaz; Robinson, Guy; Zaman, Sultan Uz; Kabir, Mamun; Sanders, Mandy; Chalmers, Rachel M.; Ahmed, Tahmeed; Jennie, Z.; Faruque, A. S. G.; Berriman, Matthew; Petri, William A.

doi:10.1093/infdis/jiy121

Cited by 52 publications

(84 citation statements)

References 14 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next-generation sequencing (NGS) has become widely available and was used successfully to resolve outbreaks and determine transmission routes (e.g. reviewed in [6]). However, not only the clonal transmission of MDR bacteria, but also the spread of multidrug resistance plasmids by horizontal gene transfer between different bacterial species represents an important mode of expansion of antimicrobial resistance genes [7].…”

Section: Introductionmentioning

confidence: 99%

Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

Peter

Bosio

Groß

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Infection of patients with multidrug-resistant (MDR) bacteria often leave very limited or no treatment options. The transfer of antimicrobial resistance genes (ARG) carrying plasmids between bacterial species by horizontal gene transfer represents an important mode of expansion of ARGs. Here, we evaluated the application of Nanopore sequencing technology in a hospital setting for monitoring the transfer and rapid evolution of antibiotic resistance plasmids within and across multiple species.Results: In 2009 we experienced an outbreak with an extensively multidrug resistant P. aeruginosa harboring the carbapenemase enzyme bla , and in 2012 the first Citrobacter freundii and Citrobacter werkmanii harboring the same enzyme were detected. Using Nanopore and Illumina sequencing we conducted a comparative analysis of all bla

show abstract

Section: Introductionmentioning

confidence: 99%

Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

Peter

Bosio

Groß

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Fully three-fourths of the infections were subclinical, but, regardless of the symptoms, children with cryptosporidiosis were more likely to become malnourished by 2 years of age (4). Potential explanations for the Cryptosporidium infection heterogeneity include differences in the pathogenicity of various Cryptosporidium species or genotypes (12) and in host genetic susceptibility.…”

mentioning

confidence: 99%

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA

Wojcik

Korpe

Marie

et al. 2020

mBio

Self Cite

View full text Add to dashboard Cite

Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and sub-Saharan Africa, where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long-term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, and yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh, namely, the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for length-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P = 3.73 × 10−8), an intronic SNP and expression quantitative trait locus (eQTL) of protein kinase C alpha (PRKCA). Each additional risk allele conferred 2.4 times the odds of Cryptosporidium-associated diarrhea in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation. IMPORTANCE Globally, diarrhea remains one of the major causes of pediatric morbidity and mortality. The initial symptoms of diarrhea can often lead to long-term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here, we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase C alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism.

show abstract

“…For example, in Bangladesh where C. hominis is the most common species (>95% of cases) and the seasonality demonstrates a summer peak corresponding to the monsoon, gp60 analysis revealed 13 different subtypes over a 2 year period (31). Some, for example IaA18R3 and IbA9G3 were present year on year, but other subtypes predominated in some years and disappeared in subsequent years (e.g., IdA15G1 was very common in 2015, but not in 2016 when IaA19R3 and IeA11G3T3 were dominant), indicating a dynamic and frequent transmission (31).…”

Section: Genotyping In Cryptosporidium Surveillance and Outbreaksmentioning

confidence: 99%

“…These findings indicate that measures to improve sanitation and hygiene would have greatest impact in these settings. Not only is there a high prevalence of Cryptosporidium in these populations, but there is also greater diversity within these species, especially noticeable in C. hominis, than is seen in industrialized countries (17,31).…”

Section: Introduction To Cryptosporidium Genotypingmentioning

confidence: 98%

Direct Sequencing of Cryptosporidium in Stool Samples for Public Health

Morris

Robinson

Swain

et al. 2019

Front. Public Health

Self Cite

View full text Add to dashboard Cite

Genetic Diversity of Cryptosporidium hominis in a Bangladeshi Community as Revealed by Whole-Genome Sequencing

Abstract: In the developing world, Cryptosporidium is one of the top causes of infant diarrhea. In a Bangladesh community we have discovered that a substantial amount of genetic recombination and genetic polymorphism in surface proteins occurs in the Cryptosporidium hominis parasite.

Cited by 52 publications

References 14 publications

Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA

Direct Sequencing of Cryptosporidium in Stool Samples for Public Health

Contact Info

Product

Resources

About