@article{fdi:010060564, title = {{S}tructure, antimicrobial activities and mode of interaction with membranes of {B}ovel {P}hylloseptins from the painted-belly leaf frog, {P}hyllomedusa sauvagii}, author = {{R}aja, {Z}. and {A}ndre, {S}. and {P}iesse, {C}. and {S}ereno, {D}enis and {N}icolas, {P}. and {F}oulon, {T}. and {O}ury, {B}runo and {L}adram, {A}.}, editor = {}, language = {{ENG}}, abstract = {{T}ranscriptomic and peptidomic analysis of skin secretions from the {P}ainted-belly leaf frog {P}hyllomedusa sauvagii led to the identification of 5 novel phylloseptins ({PLS}-{S}2 to -{S}6) and also of phylloseptin-1 ({PSN}-1, here renamed {PLS}-{S}1), the only member of this family previously isolated in this frog. {S}ynthesis and characterization of these phylloseptins revealed differences in their antimicrobial activities. {PLS}-{S}1, -{S}2, and -{S}4 (79-95% amino acid sequence identity; net charge = +2) were highly potent and cidal against {G}ram-positive bacteria, including multidrug resistant {S}. aureus strains, and killed the promastigote stage of {L}eishmania infantum, {L}. braziliensis and {L}. major. {B}y contrast, {PLS}-{S}3 (95% amino acid identity with {PLS}-{S}2; net charge = +1) and -{S}5 (net charge = +2) were found to be almost inactive against bacteria and protozoa. {PLS}-{S}6 was not studied as this peptide was closely related to {PLS}-{S}1. {D}ifferential scanning calorimetry on anionic and zwitterionic multilamellar vesicles combined with circular dichroism spectroscopy and membrane permeabilization assays on bacterial cells indicated that {PLS}-{S}1, -{S}2, and -{S}4 are structured in an amphipathic a-helix that disrupts the acyl chain packing of anionic lipid bilayers. {A}s a result, regions of two coexisting phases could be formed, one phase rich in peptide and the other lipid-rich. {A}fter reaching a threshold peptide concentration, the disruption of lipid packing within the bilayer may lead to local cracks and disintegration of the microbial membrane. {D}ifferences in the net charge, a-helical folding propensity, and/or degree of amphipathicity between {PLS}-{S}1, -{S}2 and -{S}4, and between {PLS}-{S}3 and -{S}5 appear to be responsible for their marked differences in their antimicrobial activities. {I}n addition to the detailed characterization of novel phylloseptins from {P}. sauvagii, our study provides additional data on the previously isolated {PLS}-{S}1 and on the mechanism of action of phylloseptins.}, keywords = {}, booktitle = {}, journal = {{P}los {O}ne}, volume = {8}, numero = {8}, pages = {e70782}, ISSN = {1932-6203}, year = {2013}, DOI = {10.1371/journal.pone.0070782}, URL = {https://www.documentation.ird.fr/hor/fdi:010060564}, }