{"id":6664,"date":"2023-02-17T07:07:34","date_gmt":"2023-02-17T07:07:34","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2022-temporin-b-forms-hetero-oligomers-with-temporin-l-modifies-its-membrane-activity-and-increases-the-cooperativity-of-its-antibacterial-pharmacodynamic-profile\/"},"modified":"2023-02-17T07:07:34","modified_gmt":"2023-02-17T07:07:34","slug":"2022-temporin-b-forms-hetero-oligomers-with-temporin-l-modifies-its-membrane-activity-and-increases-the-cooperativity-of-its-antibacterial-pharmacodynamic-profile","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2022-temporin-b-forms-hetero-oligomers-with-temporin-l-modifies-its-membrane-activity-and-increases-the-cooperativity-of-its-antibacterial-pharmacodynamic-profile\/","title":{"rendered":"2022 &#8211; Temporin B Forms Hetero-Oligomers with Temporin L, Modifies Its Membrane Activity, and Increases the Cooperativity of Its Antibacterial Pharmacodynamic Profile"},"content":{"rendered":"<p>The pharmacodynamic profile of antimicrobial peptides (AMPs) and their\u00a0in vivo\u00a0synergy are two factors that are thought to restrict resistance evolution and ensure their conservation. The frog\u00a0Rana temporaria\u00a0secretes a family of closely related AMPs, temporins A-L, as an effective chemical dermal defence. The antibacterial potency of temporin L has been shown to increase synergistically in combination with both temporins B and A but this is modest. Here we show that the less potent temporin B enhances the cooperativity of the\u00a0in vitro\u00a0antibacterial activity of the more potent temporin L against EMRSA-15 and that this may be associated with an altered interaction with the bacterial plasma membrane, a feature critical for the antibacterial activity of most AMPs. Addition of buforin II, a histone H2A fragment, can further increase the cooperativity. Molecular dynamics simulations indicate temporins B and L readily form hetero-oligomers in models of Gram-positive bacterial plasma membranes. Patch-clamp studies show transmembrane ion conductance is triggered with lower amounts of both peptides and more quickly, when used in combination, but conductance is of a lower amplitude and pores are smaller. Temporin B may therefore act by forming temporin L\/B hetero-oligomers that are more effective than temporin L homo-oligomers at bacterial killing and\/or by reducing the probability of the latter forming until a threshold concentration is reached. Exploration of the mechanism of synergy between AMPs isolated from the same organism may therefore yield antibiotic combinations with advantageous pharmacodynamic properties.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45,129],"resource_type":[75],"application_areas":[99],"therapeutic_areas":[],"target_categories":[341],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6664","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","products_tags-vesicle-prep-pro","resource_type-publication","application_areas-pores-and-toxins","target_categories-pores-and-toxins"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6664","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6664"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6664"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6664"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6664"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6664"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6664"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6664"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6664"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6664"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}