Catalase impairs <i>Leishmania mexicana</i> development and virulence

Sádlová, Jovana; Podešvová, Lucie; Bečvář, Tomáš; Bianchi, C.; Gerasimov, Evgeny S.; Saura, Andreu; Glanzová, Kristýna; Leštinová, Tereza; Matveeva, Nadezhda S.; Chmelová, Ľubomíra; Mlacovská, Denisa; Spitzová, Tatiana; Vojtková, Barbora; Volf, Petr; Yurchenko, Vyacheslav; Kraeva, Natalya

doi:10.1080/21505594.2021.1896830

Cited by 11 publications

(7 citation statements)

References 107 publications

(65 reference statements)

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“…Similarly, catalase-expressing Leishmania mexicana had their development in insects and mice severely compromised. Taken together, these data support the hypothesis that the absence of catalase in some trypanosomatids is essential for the emergence of a dixenous life cycle due to the regulatory role of H 2 O 2 in the transition from insect to the mammalian stages (Freire et al, 2017;Kraeva et al, 2017;Horaḱováet al, 2020;Sadlováet al, 2021). Curiously, tsetse flies have not been found hosting catalase-carrying monoxenous trypanosomatids in the wild, although species of Leishmaniinae clade are widely identified in dipteran insects.…”

Section: Discussionsupporting

confidence: 74%

Aedes aegypti Infection With Trypanosomatid Strigomonas culicis Alters Midgut Redox Metabolism and Reduces Mosquito Reproductive Fitness

Bombaça

Gandara

Ennes-Vidal

et al. 2021

Front. Cell. Infect. Microbiol.

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Aedes aegypti mosquitoes transmit arboviruses of important global health impact, and their intestinal microbiota can influence vector competence by stimulating the innate immune system. Midgut epithelial cells also produce toxic reactive oxygen species (ROS) by dual oxidases (DUOXs) that are essential players in insect immunity. Strigomonas culicis is a monoxenous trypanosomatid that naturally inhabits mosquitoes; it hosts an endosymbiotic bacterium that completes essential biosynthetic pathways of the parasite and influences its oxidative metabolism. Our group previously showed that S. culicis hydrogen peroxide (H2O2)-resistant (WTR) strain is more infectious to A. aegypti mosquitoes than the wild-type (WT) strain. Here, we investigated the influence of both strains on the midgut oxidative environment and the effect of infection on mosquito fitness and immunity. WT stimulated the production of superoxide by mitochondrial metabolism of midgut epithelial cells after 4 days post-infection, while WTR exacerbated H2O2 production mediated by increased DUOX activity and impairment of antioxidant system. The infection with both strains also disrupted the fecundity and fertility of the females, with a greater impact on reproductive fitness of WTR-infected mosquitoes. The presence of these parasites induced specific transcriptional modulation of immune-related genes, such as attacin and defensin A during WTR infection (11.8- and 6.4-fold, respectively) and defensin C in WT infection (7.1-fold). Thus, we propose that A. aegypti oxidative response starts in early infection time and does not affect the survival of the H2O2-resistant strain, which has a more efficient antioxidant system. Our data provide new biological aspects of A. aegypti–S. culicis relationship that can be used later in alternative vector control strategies.

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Section: Discussionsupporting

confidence: 74%

Aedes aegypti Infection With Trypanosomatid Strigomonas culicis Alters Midgut Redox Metabolism and Reduces Mosquito Reproductive Fitness

Bombaça

Gandara

Ennes-Vidal

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Leishmania mexicana (isolate MNYC/BZ/62/M379) genome was also assembled de novo with Flye v. 2.8.3 [ 47 ] using only PacBio reads reported previously [ 48 ] and genome size parameter 32 Mb, which is the size of reference L . mexicana MHOM/GT/2001/U1103 assembly [ 49 ] from the TriTrypDB release 52 [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana

et al. 2021

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Background Telomeres are indispensable for genome stability maintenance. They are maintained by the telomere-associated protein complex, which include Ku proteins and a telomerase among others. Here, we investigated a role of Ku80 in Leishmania mexicana. Leishmania is a genus of parasitic protists of the family Trypanosomatidae causing a vector-born disease called leishmaniasis. Methodology/Principal findings We used the previously established CRISPR/Cas9 system to mediate ablation of Ku80- and Ku70-encoding genes in L. mexicana. Complete knock-outs of both genes were confirmed by Southern blotting, whole-genome Illumina sequencing, and RT-qPCR. Resulting telomeric phenotypes were subsequently investigated using Southern blotting detection of terminal restriction fragments. The genome integrity in the Ku80- deficient cells was further investigated by whole-genome sequencing. Our work revealed that telomeres in the ΔKu80 L. mexicana are elongated compared to those of the wild type. This is a surprising finding considering that in another model trypanosomatid, Trypanosoma brucei, they are shortened upon ablation of the same gene. A telomere elongation phenotype has been documented in other species and associated with a presence of telomerase-independent alternative telomere lengthening pathway. Our results also showed that Ku80 appears to be not involved in genome stability maintenance in L. mexicana. Conclusion/Significance Ablation of the Ku proteins in L. mexicana triggers telomere elongation, but does not have an adverse impact on genome integrity.

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“…Total DNA of 9 virus-positive and 1 virus-negative (13 Th) L. major strains was isolated as described previously [35]. The whole-genome sequencing libraries were prepared with TruSeq DNA PCR-free Kit (Illumina, San Diego, CA, US) and sequenced using HiSeq 4000 platform (Illumina) in paired-end mode with read length of 150 bp at SkolTech Genomics core facility (Moscow, Russia).…”

Section: Whole-genome Sequencing and Read Mappingmentioning

confidence: 99%

Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins

Kostygov

Grybchuk

Kleschenko

et al. 2021

Viruses

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Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.

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Catalase impairs Leishmania mexicana development and virulence

Cited by 11 publications

References 107 publications

Aedes aegypti Infection With Trypanosomatid Strigomonas culicis Alters Midgut Redox Metabolism and Reduces Mosquito Reproductive Fitness

Aedes aegypti Infection With Trypanosomatid Strigomonas culicis Alters Midgut Redox Metabolism and Reduces Mosquito Reproductive Fitness

Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana

Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins

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