{"id":15989,"date":"2024-09-18T08:50:37","date_gmt":"2024-09-18T08:50:37","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=15989"},"modified":"2024-09-18T08:50:37","modified_gmt":"2024-09-18T08:50:37","slug":"2024-substrate-dependence-of-transport-coupling-and-phenotype-of-a-small-multidrug-resistance-transporter-in-pseudomonas-aeruginosa","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2024-substrate-dependence-of-transport-coupling-and-phenotype-of-a-small-multidrug-resistance-transporter-in-pseudomonas-aeruginosa\/","title":{"rendered":"2024 &#8211; Substrate dependence of transport coupling and phenotype of a small multidrug resistance transporter in Pseudomonas aeruginosa"},"content":{"rendered":"<p>Small multidrug resistance (SMR) transporters are key players in the defense of multidrug-resistant pathogens to toxins and other homeostasis-perturbing compounds. However, recent evidence demonstrates that EmrE, an SMR from\u00a0<i>Escherichia coli<\/i>\u00a0and a model for understanding transport, can also induce susceptibility to some compounds by drug-gated proton leak. This runs down the \u2206pH component of the proton-motive force (PMF), reducing the viability of the affected bacteria. Proton leak may provide an unexplored drug target distinct from the targets of most known antibiotics. Activating proton leak requires an SMR to be merely present, rather than be the primary resistance mechanism, and dissipates the energy source for many other efflux pumps. PAsmr, an EmrE homolog from\u00a0<i>Pseudomonas aeruginosa<\/i>, transports many EmrE substrates in cells and purified systems. We hypothesized that PAsmr, like EmrE, may confer susceptibility to some compounds via drug-gated proton leak. Growth assays of\u00a0<i>E. coli<\/i>\u00a0expressing PAsmr displayed substrate-dependent resistance and susceptibility phenotypes, and\u00a0<i>in vitro<\/i>\u00a0solid-supported membrane electrophysiology experiments revealed that PAsmr performs both antiport and substrate-gated proton uniport, demonstrating the same functional promiscuity observed in EmrE. Growth assays of\u00a0<i>P. aeruginosa<\/i>\u00a0strain PA14 demonstrated that PAsmr contributes resistance to some antimicrobial compounds, but no growth defect is observed with susceptibility substrates, suggesting\u00a0<i>P. aeruginosa<\/i>\u00a0can compensate for the proton leak occurring through PAsmr. These phenotypic differences between\u00a0<i>P. aeruginosa<\/i>\u00a0and\u00a0<i>E. coli<\/i>\u00a0advance our understanding of the underlying resistance mechanisms in\u00a0<i>P. aeruginosa<\/i>\u00a0and prompt further investigation into the role that SMRs play in antibiotic resistance in pathogens.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[],"resource_type":[75],"application_areas":[53,108],"therapeutic_areas":[143],"target_categories":[60],"target_families":[494],"targets":[481,495],"resource_keyword":[],"class_list":["post-15989","resource_library","type-resource_library","status-publish","hentry","resource_type-publication","application_areas-assay-development-and-validation","application_areas-transporters","therapeutic_areas-assay-development-and-validation","target_categories-transporters","target_families-small-multidrug-resistance-smr-transporters","targets-emre","targets-pasmr"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/15989","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=15989"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=15989"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=15989"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=15989"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=15989"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=15989"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=15989"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=15989"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=15989"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}