Dietary para-aminobenzoic acid, uric acid, and antibiotics modulate the susceptibility of Anopheles darlingi and Anopheles albimanus to Plasmodium berghei

Breno dos Anjos Costa^1,2Raquel Godoy^1,2Lucas Henrique-Gomes¹Rosa Amélia Gonçalves Santana³Silvia Cássia Brandão Justiniano⁴STEFANIE COSTA PINTO LOPES^4,5Wuelton Monteiro^3,6Gisely Melo^3,6Nagila Francinete Costa Secundino^1,2,3,6PAULO FILEMON PAOLUCCI PIMENTA^1,2,3,6*

• ¹Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil
• ²Programa de Pós-Graduação em Ciências da Saúde, Instituto René Rachou, Belo Horizonte, Brazil
• ³Programa de Pós-Graduação em Medicina Tropical, Fundação de Medicina Tropical Heitor Vieira Dourado, Univesidade do Estado do Amazonas, Manaus, Brazil
• ⁴Unidade de Entomologia Nelson Ferreira Fé (UENFF), Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
• ⁵Instituto Leônidas & Maria Deane, FIOCRUZ-Amazônia, Manaus, Brazil
• ⁶Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil

Malaria, caused by Plasmodium, is transmitted to humans through the bite of infected Anopheles mosquitoes. Anopheles darlingi and Anopheles albimanus are primary vectors in South and Central America, with An. darlingi the main vector in the Amazon region, which has the highest malaria levels in the Americas. Notwithstanding advancements in comprehending Anopheles–Plasmodium interactions in malaria vectors, information regarding these processes in New World vectors is nonetheless scarce. The limited understanding of An. darlingi is mainly attributable to the absence of experimental models suitable for its study. Researchers frequently utilize murine Plasmodium species, such as Plasmodium berghei, owing to their convenience in laboratory settings beyond endemic areas. Specific chemicals consumed by mosquitoes can affect the efficiency of Plasmodium infection. This study evaluates the susceptibility of An. darlingi and An. albimanus to P. berghei under different post-infection treatments, including para-aminobenzoic acid (PABA), uric acid, and penicillin/streptomycin (Pen/Strep). Dietary supplementation with PABA, whether administered alone or in combination, influences susceptibility in both species. P. berghei sporozoites were detected in the hemolymph but not in the salivary glands until 28 days post-infection. This study is the first investigation to demonstrate that post-infection dietary treatments might influence the susceptibility of American vectors to P. berghei, hence broadening the scope for research on infection dynamics and parasite management mechanisms.