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Here, we evaluated functional\/biochemical LPG properties from six <jats:italic>Leishmania amazonensis<\/jats:italic> strains from different hosts\/clinical forms. LPGs from three strains (GV02, BA276, and LV79) had higher pro\u2010inflammatory profiles for most of the mediators, including tumor necrosis factor alpha and interleukin 6. For this reason, glycoconjugates from all strains were biochemically characterized and had polymorphisms in their repeat units. They consisted of three types: type I, repeat units devoid of side chains; type II, containing galactosylated side chains; and type III, containing glucosylated side chains. No relationship was observed between LPG type and the pro\u2010inflammatory properties. Finally, to evaluate the susceptibility against antileishmanial agents, two strains with high (GV02, BA276) and one with low (BA336) pro\u2010inflammatory activity were selected for chemotherapeutic tests in THP\u20101 cells. All analyzed strains were susceptible to amphotericin B (AmB) but displayed various responses against miltefosine (MIL) and glucantime (GLU). The GV02 strain (canine visceral leishmaniasis) had the highest IC<jats:sub>50<\/jats:sub> for MIL (3.34\u2009\u03bcM), whereas diffuse leishmaniasis strains (BA276 and BA336) had a higher IC<jats:sub>50<\/jats:sub> for GLU (6.87\u201312.19\u2009mM). The highest IC<jats:sub>50<\/jats:sub> against MIL shown by the GV02 strain has an impact on clinical management. Miltefosine is the only drug approved for dog treatment in Brazil. Further studies into drug susceptibility of <jats:italic>L. amazonensis<\/jats:italic> strains are warranted, especially in areas where dog infection by this species overlaps with those caused by <jats:italic>Leishmania infantum<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cbin.11880","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T18:46:09Z","timestamp":1661280369000},"page":"1947-1958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>Leishmania amazonensis<\/i> from distinct clinical forms\/hosts has polymorphisms in Lipophosphoglycans, displays variations in immunomodulatory properties and, susceptibility to antileishmanial drugs"],"prefix":"10.1002","volume":"46","author":[{"given":"Felipe D.","family":"R\u00eago","sequence":"first","affiliation":[{"name":"Biotechnology Applied to Pathogens (BAP), Instituto Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ) Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila d. 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