{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T13:50:51Z","timestamp":1775656251026,"version":"3.50.1"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      \u03b2-Barrel outer membrane proteins (OMPs) perform critical functions in gram-negative bacteria including outer membrane biogenesis, nutrient acquisition, and efflux. OMPs are folded by the \u03b2-barrel assembly machinery (BAM) with BamA as a central and essential component. BamK, a\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      BamA paralog, can functionally replace BamA; however, native\n                      <jats:italic toggle=\"yes\">bamK<\/jats:italic>\n                      expression and a role for BamK have not been reported. Here, we identify mutations in a two-component signal transduction system that activate expression of\n                      <jats:italic toggle=\"yes\">bamK<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      . Selections for\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      mutants resistant to a BamA-targeting antibacterial macrocyclic peptide, PTB1-1, yield on-target and off-target mutations. On-target\n                      <jats:italic toggle=\"yes\">bamA<\/jats:italic>\n                      mutations overlap with previously described positions in the PTB1-1 binding site. Off-target mutations map to three distinct genes,\n                      <jats:italic toggle=\"yes\">oqxR<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ramR<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">baeS<\/jats:italic>\n                      . Transcriptomics analyses indicate that mutations in\n                      <jats:italic toggle=\"yes\">baeS,<\/jats:italic>\n                      a sensor histidine kinase, activate\n                      <jats:italic toggle=\"yes\">bamK<\/jats:italic>\n                      expression, and these mutants render\n                      <jats:italic toggle=\"yes\">bamA<\/jats:italic>\n                      dispensable for bacterial growth. Our results demonstrate that BamK can functionally substitute for the essential function of BamA\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">bamK<\/jats:italic>\n                      expression is controlled by a two-component signal transduction system that responds to envelope stress in gram-negative bacteria. These findings provide insight into possible roles for BamK and considerations for future efforts to develop antibiotics targeting OMP folding.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The complex envelope of gram-negative bacteria is a critical structure. It is assembled and maintained by multiple essential pathways, all of which, including the \u03b2-barrel assembly machinery (BAM) complex, have been the focus of novel antibiotic discovery efforts. Species in the genus\n                        <jats:italic toggle=\"yes\">Klebsiella<\/jats:italic>\n                        encode a paralog to the BAM complex component BamA, called BamK, but the importance and role of this protein has remained a mystery. Leveraging mutants resistant to a recently discovered BamA inhibitor, we describe how activation of the BaeSR envelope stress response system can activate\n                        <jats:italic toggle=\"yes\">bamK<\/jats:italic>\n                        expression to overcome the loss of BamA or its function both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . These findings provide important insights into BamK,\n                        <jats:italic toggle=\"yes\">Klebsiella<\/jats:italic>\n                        biology, gram-negative stress responses, and targeting outer membrane protein folding as an antibacterial strategy.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03497-24","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:02:57Z","timestamp":1774270977000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The BaeSR two-component system activates\n                    <i>bamK<\/i>\n                    , a paralog of the essential \u03b2-barrel foldase\n                    <i>bamA<\/i>\n                    , in\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2289-0214","authenticated-orcid":false,"given":"Kelly M.","family":"Storek","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina","family":"Reeder","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin K.","family":"Murchison","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Skippington","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Genentech, Inc.","place":["South San Francisco, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-4248","authenticated-orcid":true,"given":"Steven T.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Genentech, Inc.","place":["South San Francisco, 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