Snake venoms are important
sources of bioactive molecules, including
those with antiparasitic activity. Cathelicidins form a class of such
molecules, which are produced by a variety of organisms. Batroxicidin
(BatxC) is a cathelicidin found in the venom of the common lancehead
(Bothrops atrox). In the present work, BatxC and
two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1,
were assessed for their microbicidal activity. All three peptides
showed a broad-spectrum activity on Gram-positive and -negative bacteria,
as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular
dichroism (CD) and nuclear magnetic resonance (NMR) data indicated
that the three peptides changed their structure upon interaction with
membranes. Biomimetic membrane model studies demonstrated that the
peptides exert a permeabilization effect in prokaryotic membranes,
leading to cell morphology distortion, which was confirmed by atomic
force microscopy (AFM). The molecules considered in this work exhibited
bactericidal and leishmanicidal activity at low concentrations, with
the AFM data suggesting membrane pore formation as their mechanism
of action. These peptides stand as valuable prototype drugs to be
further investigated and eventually used to treat bacterial and protozoal
infections.