{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:01:39Z","timestamp":1789851699636,"version":"4.0.1"},"posted":{"date-parts":[[2026,3,18]]},"group-title":"Microbiology","reference-count":124,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["2R01EY026171"],"award-info":[{"award-number":["2R01EY026171"]}]},{"name":"NIH","award":["R01EY032956"],"award-info":[{"award-number":["R01EY032956"]}]},{"name":"TearSolutions, Inc","award":["Unrestricted gift"],"award-info":[{"award-number":["Unrestricted gift"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lacritin is a tear, saliva, plasma and cerebrospinal fluid glycoprotein with broad polypharmacology. Its protease generated N-104 proteoform endogenous in tears (and likely elsewhere) is bactericidal and synergizes with the tear thrombin peptide GKY20. In the pathogenic and multidrug resistant PA14 strain of\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  , we recently discovered that N-104 at subinhibitory and inhibitory concentrations binds to the outer-membrane lipoprotein YaiW to gain access to the periplasm where it targets and inhibits the inner-membrane ferrous iron transporter FeoB (of FeoABC) as well as PotH, a subunit of the polyamine transporter PotFGHI. Further, PA14 gene expression shifts toward anaerobic respiratory pathways. Here we report N-104-associated transcriptional changes pointing to a reduction in: (i) virulence, (ii) fitness, (iii) metabolism, (iv) stress response, (v) proteostasis, (vii) quorum sensing, and (viii) survival under anaerobic conditions. Upregulated genes are directed towards enhancing PA14: (i) multidrug and (ii) tellurite efflux, coupled with a seemingly PA14 survival attempt at (iii) anaerobic respiration, (iv) translational fidelity and (v) metabolism. The overlap with aminoglycosides (4.3%), \u03b2-lactams (0%), cyclic peptides (2.5%), fluoroquinilones (0%) and macrolide (1.9%) classes of antibiotics in\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  was minimal. Thus, N-104 appears to widely perturb PA14 fundamental processes in a distinctive manner.\n                <\/jats:p>","DOI":"10.64898\/2026.03.17.712309","type":"posted-content","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:30:10Z","timestamp":1773891010000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinctive Lacritin Cleavage-Potentiated Bactericidal Alteration of the\n                  <i>P. aeruginosa<\/i>\n                  Transcriptome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3867-1611","authenticated-orcid":false,"given":"Mohammad","family":"Sharifian Gh","sequence":"first","affiliation":[{"name":"Departments of Cell Biology, University of Virginia, Charlottesville VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2332-0125","authenticated-orcid":false,"given":"Fatemeh","family":"Norouzi","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology, University of Virginia, Charlottesville VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5311-2650","authenticated-orcid":false,"given":"Gordon W.","family":"Laurie","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology, University of Virginia, Charlottesville VA, USA"},{"name":"Biomedical Engineering, University of Virginia, Charlottesville VA, USA"},{"name":"Ophthalmology, University of Virginia, Charlottesville VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091913050491000_2026.03.17.712309v2.1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4748"},{"key":"2026091913050491000_2026.03.17.712309v2.2","doi-asserted-by":"crossref","first-page":"110580","DOI":"10.1016\/j.jbc.2025.110580","article-title":"In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms","volume":"301","year":"2025","journal-title":"J. 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