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Comprehensive analysis of flavohemoprotein copy number variation in Giardia intestinalis: exploring links to metronidazole resistance.
Korenková, Vlasta; Weisz, Filip; Perglerová, Aneta; Cacciò, Simone M; Nohýnková, Eva; Tumová, Pavla.
Afiliación
  • Korenková V; Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. vlasta.korenkova@lf1.cuni.cz.
  • Weisz F; Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Perglerová A; Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Cacciò SM; Department of Infectious Diseases, Istituto Superiore Di Sanita, Rome, Italy.
  • Nohýnková E; Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Tumová P; Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
Parasit Vectors ; 17(1): 336, 2024 Aug 10.
Article en En | MEDLINE | ID: mdl-39127700
ABSTRACT

BACKGROUND:

Giardiasis, caused by the protozoan parasite Giardia intestinalis, often presents a treatment challenge, particularly in terms of resistance to metronidazole. Despite extensive research, markers for metronidazole resistance have not yet been identified.

METHODS:

This study analysed 28 clinical samples of G. intestinalis from sub-assemblage AII, characterised by varying responses to metronidazole treatment. We focussed on copy number variation (CNV) of the multi-copy flavohemoprotein gene, analysed using digital polymerase chain reaction (dPCR) and next generation sequencing (NGS). Additionally, chromosomal ploidy was tested in 18 of these samples. Flavohemoprotein CNV was also assessed in 17 samples from other sub-assemblages.

RESULTS:

Analyses revealed variable CNVs of the flavohemoprotein gene among the isolates, with no correlation to clinical metronidazole resistance. Discrepancies in CNVs detected from NGS data were attributed to biases linked to the whole genome amplification. However, dPCR helped to clarify these discrepancies by providing more consistent CNV data. Significant differences in flavohemoprotein CNVs were observed across different G. intestinalis sub-assemblages. Notably, Giardia exhibits a propensity for aneuploidy, contributing to genomic variability within and between sub-assemblages.

CONCLUSIONS:

The complexity of the clinical metronidazole resistance in Giardia is influenced by multiple genetic factors, including CNVs and aneuploidy. No significant differences in the CNV of the flavohemoprotein gene between isolates from metronidazole-resistant and metronidazole-sensitive cases of giardiasis were found, underscoring the need for further research to identify reliable genetic markers for resistance. We demonstrate that dPCR and NGS are robust methods for analysing CNVs and provide cross-validating results, highlighting their utility in the genetic analyses of this parasite.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Medicamentos / Giardiasis / Giardia lamblia / Variaciones en el Número de Copia de ADN / Metronidazol / Antiprotozoarios Límite: Humans Idioma: En Revista: Parasit Vectors Año: 2024 Tipo del documento: Article País de afiliación: República Checa

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Medicamentos / Giardiasis / Giardia lamblia / Variaciones en el Número de Copia de ADN / Metronidazol / Antiprotozoarios Límite: Humans Idioma: En Revista: Parasit Vectors Año: 2024 Tipo del documento: Article País de afiliación: República Checa
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