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The gut of hematophagous arthropods stores and slowly digests host blood and represents the primary gateway for transmitted pathogens. The initial step in blood degradation is induced lysis of host red blood cells (hemolysis), which releases hemoglobin for subsequent processing by digestive proteolytic enzymes. The activity cycles and characteristics of hemolysis in vectors are poorly understood. Hence, we investigated hemolysis in two evolutionarily distant blood-feeding arthropods: The mosquito <jats:italic>Culex pipiens<\/jats:italic> and the soft tick <jats:italic>Argas persicus<\/jats:italic>, both of which are important human and veterinary disease vectors. Hemolysis in both species was cyclical after blood meal ingestion. Maximum digestion occurs under slightly alkaline conditions in females. Hemolytic activity appears to be of lipoid origin in <jats:italic>C<\/jats:italic>. <jats:italic>pipiens<\/jats:italic> and enzymatic activity (proteolytic) in <jats:italic>A<\/jats:italic>. <jats:italic>persicus<\/jats:italic>. We have assessed the effect of pH, incubation time, and temperature on hemolytic activity and the hemolysin. The susceptibility of red blood cells from different hosts to the hemolysin and the effect of metabolic inhibition of hemolytic activity were assessed. We conclude that in <jats:italic>C<\/jats:italic>. <jats:italic>pipiens<\/jats:italic> and <jats:italic>A<\/jats:italic>. <jats:italic>persicus<\/jats:italic> midgut hemolysins control the amplitude of blood lysis step to guarantee an efficient blood digestion.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009151","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T18:59:43Z","timestamp":1612637983000},"page":"e0009151","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparison of the hemolysis machinery in two evolutionarily distant blood-feeding arthropod vectors of human diseases"],"prefix":"10.1371","volume":"15","author":[{"given":"Moataza","family":"Dorrah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaima","family":"Bensaoud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-5534","authenticated-orcid":true,"given":"Amr A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Sojka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taha T. 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