{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:36:12Z","timestamp":1785429372955,"version":"3.56.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AI170962"],"award-info":[{"award-number":["RO1AI170962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["JP23734491 (23K13867)"],"award-info":[{"award-number":["JP23734491 (23K13867)"]}]},{"name":"The Hokuto Bio-science Promotion Foundation"},{"name":"The Nakajima Foundation"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2025,10,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gram-negative bacteria harbor an outer membrane that physically protects them from the penetration of antibiotics into the cells. This barrier makes it challenging to develop antibiotics that effectively kill Gram-negative pathogens. The entomopathogenic bacterium\n                      <jats:italic toggle=\"yes\">Photorhabdus<\/jats:italic>\n                      species produces various bioactive molecules and is receiving attention as an attractive source of novel antibiotics. We identified a novel antipseudomonal antibiotic, pioamide, from the culture supernatant of\n                      <jats:italic toggle=\"yes\">Photorhabdus khanii<\/jats:italic>\n                      HGB1456, a strain that produces darobactin, which selectively kills Gram-negative bacteria. Pioamide, a pentapeptide antibiotic with a molecular weight of 704, exhibits selective activity against\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      but does not exhibit any activity against other bacteria or human cell lines. Whole-genome sequencing of spontaneous pioamide-resistant mutants of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      revealed mutations in\n                      <jats:italic toggle=\"yes\">pmrB<\/jats:italic>\n                      , which encodes a two-component regulatory system response regulator that modifies the lipopolysaccharide composition in Gram-negative bacteria, conferring pioamide resistance to\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . Furthermore, the susceptibility of both\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      PAO1 and the mutant strain P\u03946-Pore, which overexpresses porins and lacks six efflux pumps, to pioamide was identical, indicating that porins and the efflux pump exert no significant effect on the activity of pioamide. These results suggest that pioamide either targets the cell surface of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      or is incorporated via a species-specific uptake mechanism. Our findings highlight the potential of\n                      <jats:italic toggle=\"yes\">Photorhabdus<\/jats:italic>\n                      strains as an attractive source for the discovery of antibiotics active against Gram-negative pathogens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The rise of multidrug-resistant Gram-negative bacteria is a growing threat to global public health. Narrow-spectrum antibiotics minimize disruption of the host microbiota and reduce the risk of resistance development in off-target bacteria. In the field of antibacterial discovery, developing compounds effective against\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      remains particularly challenging. Although\n                      <jats:italic toggle=\"yes\">Photorhabdus<\/jats:italic>\n                      species are known to produce various antibiotics, their potential remains largely underexplored. In this study, we applied differential screening to a highly concentrated culture extract of\n                      <jats:italic toggle=\"yes\">Photorhabdus khanii<\/jats:italic>\n                      HGB1456 and discovered pioamide, a novel cyclic peptide with unusual selective activity against\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . Mutations in pmrB confer pioamide resistance to\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . However, the mechanism of action is distinct from that of colistin, which also involves resistance conferred by\n                      <jats:italic toggle=\"yes\">pmrB<\/jats:italic>\n                      mutations. These findings underscore the untapped potential of\n                      <jats:italic toggle=\"yes\">Photorhabdus<\/jats:italic>\n                      species as an attractive source of species-specific antibiotics and highlight the utility of differential screening for discovering compounds with targeted antibacterial activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01123-25","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T13:00:28Z","timestamp":1758718828000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A novel homoarginine-containing cyclic peptide pioamide with selective antipseudomonal activity isolated from the nematode symbiont\n                    <i>Photorhabdus khanii<\/i>"],"prefix":"10.1128","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-5115","authenticated-orcid":true,"given":"Yu","family":"Imai","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0244rem06","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Aqua Regeneration, Shinshu University","place":["Nagano, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangkeun","family":"Son","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ahky613","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Antimicrobial Discovery Center, Northeastern University","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Sasaki","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ahky613","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Antimicrobial Discovery Center, Northeastern 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