Novel systems to study vector-pathogen interactions in malaria

© 2023 Parres-Mercader, Pance and Gómez-Díaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating “de novo” genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.Peer reviewe

Cambio en la expresión del metabolismo en células renales del túbulo proximal humano. Efectos del shear stress

Las células del túbulo proximal renal están continuamente expuestas al estímulo mecánico que genera el filtrado glomerular. Este estímulo, denominada shear stress, induce cambios a nivel fenotípico y también funcional, por lo que es de vital importancia reproducir este entorno para estudiar estas células in vitro. El siguiente estudio se centra en determinar cambios en la expresión génica del metabolismo de las células RPTEC sometidas a shear stress. Se analiza también el consumo de oxígeno y por último se pretende generar un knock-out para la proteína AMPK, encargada de regular la homeostasis energética. Los resultados obtenidos muestran un aumento en la captación de oxígeno de las células sometidas a shear stress, pudiéndose relacionar con un incremento en la actividad metabólica. Sin embargo, y aunque se detectan ciertos cambios en los niveles de expresión génica, los resultados obtenidos no indican de forma concluyente un aumento del metabolismo. Por último, en este estudio no se logró editar genéticamente las células RPTEC. Este trabajo contribuye en la evidencia de que el estímulo mecánico producido por el shear stress tiene efectos relevantes en las células del túbulo proximal, poniendo de manifiesto la necesidad de trabajar con cultivos y dispositivos que mimeticen las condiciones in vivo para poder extrapolar de una forma más fiable los resultados obtenidos in vitro. <br /

El paper del sistema CRISPR/Cas en la modulació de la virulència

El locus CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) junt amb seqüències associades gens cas i proteïnes Cas (CRISPR associated genes) formen el sistema immune adaptatiu CRISPR/Cas, el qual és present en la majoria de Archaea i més del 40% en bacteris. S'han classificat en tres tipus (I-III) i 11 subtipus (IA-F, IIA-C i IIIA-B), basats en la filogènia i el mecanisme molecular d'acció. Aquests sistemes poden actuar com a barrera de la transferència horitzontal de gens, fonamental per a l'evolució dels procariotes. A més estudis recents han demostrar funcionalitats alternatives del sistema CRISPR/Cas, basat en la capacitat de controlar la transcripció endògena i regular importants fenotips bacterians com ara la patogenicitat. L'objectiu és veure com les diferents funcions d'aquest sistema pot afectar en la modulació de la virulència de certs bacteris patògens

Prevalence of SARS-CoV-2 and co-occurrence/co-infection with malaria during the first wave of the pandemic (the Burkina Faso case)

Africa accounts for 1.5% of the global coronavirus disease 2019 (COVID-19) cases and 2.7% of deaths, but this low incidence has been partly attributed to the limited testing capacity in most countries. In addition, the population in many African countries is at high risk of infection with endemic infectious diseases such as malaria. Our aim is to determine the prevalence and circulation of SARS-CoV-2 variants, and the frequency of co-infection with the malaria parasite. We conducted serological tests and microscopy examinations on 998 volunteers of different ages and sexes in a random and stratified population sample in Burkina-Faso. In addition, nasopharyngeal samples were taken for RT-qPCR of SARS-COV-2 and for whole viral genome sequencing. Our results show a 3.2% and a 2.5% of SARS-CoV-2 seroprevalence and PCR positivity; and 22% of malaria incidence, over the sampling period, with marked differences linked to age. Importantly, we found 2 cases of confirmed co-infection and 8 cases of suspected co-infection mostly in children and teenagers. Finally, we report the genome sequences of 13 SARS-CoV-2 isolates circulating in Burkina Faso at the time of analysis, assigned to lineages: A.19, A.21, B.1.1.404, B.1.1.118, B.1 and grouped into clades; 19B, 20A and 20B. This is the first population-based study about SARS-CoV-2 and malaria in Burkina Faso during the first wave of the pandemic, providing a relevant estimation of the real prevalence of SARS-CoV-2 and variants circulating in this Sub-Saharan African country. Besides, it highlights the low frequency of co-infection with malaria in African communities.This research work received funding from by the European Commission NextGenerationEU (Regulation EU 2020/2094) and grant 202020E159 through CSIC Global Health Platform (PTI Salud Global).N

Prevalence of SARS-CoV-2 and co-infection with malaria during the first wave of the pandemic (the Burkina Faso case)

Peer reviewed: TrueAcknowledgements: We would like to thank all volunteers who participated in this study, as well as the local authorities and communities in Burkina Faso for their support. We also thank the IPBLN, IRSS and IBV core facilities for their support to project activities.Africa accounts for 1.5% of the global coronavirus disease 2019 (COVID-19) cases and 2.7% of deaths, but this low incidence has been partly attributed to the limited testing capacity in most countries. In addition, the population in many African countries is at high risk of infection with endemic infectious diseases such as malaria. Our aim is to determine the prevalence and circulation of SARS-CoV-2 variants, and the frequency of co-infection with the malaria parasite. We conducted serological tests and microscopy examinations on 998 volunteers of different ages and sexes in a random and stratified population sample in Burkina-Faso. In addition, nasopharyngeal samples were taken for RT-qPCR of SARS-CoV-2 and for whole viral genome sequencing. Our results show a 3.2 and a 2.5% of SARS-CoV-2 seroprevalence and PCR positivity; and 22% of malaria incidence, over the sampling period, with marked differences linked to age. Importantly, we found 8 cases of confirmed co-infection and 11 cases of suspected co-infection mostly in children and teenagers. Finally, we report the genome sequences of 13 SARS-CoV-2 isolates circulating in Burkina Faso at the time of analysis, assigned to lineages A.19, A.21, B.1.1.404, B.1.1.118, B.1 and grouped into clades; 19B, 20A, and 20B. This is the first population-based study about SARS-CoV-2 and malaria in Burkina Faso during the first wave of the pandemic, providing a relevant estimation of the real prevalence of SARS-CoV-2 and variants circulating in this Western African country. Besides, it highlights the non-negligible frequency of co-infection with malaria in African communities