{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:46:07Z","timestamp":1765889167356,"version":"3.41.2"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R00AI139344"],"award-info":[{"award-number":["R00AI139344"]}]},{"DOI":"10.13039\/100014147","name":"Charles E. Kaufman Foundation","doi-asserted-by":"crossref","award":["KA2021-121928"],"award-info":[{"award-number":["KA2021-121928"]}],"id":[{"id":"10.13039\/100014147","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Damon Runyon Dale E. Frey Award for Breakthrough Scientists"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Many pathogenic bacteria, including\n            <jats:italic>Legionella pneumophila<\/jats:italic>\n            , infect humans from environmental reservoirs. To survive in these reservoirs, bacteria must withstand microbe-on-microbe competition. We previously discovered that\n            <jats:italic>L. pneumophila<\/jats:italic>\n            can compete with neighboring bacteria via an antimicrobial metabolite called homogentisic acid (HGA). Curiously,\n            <jats:italic>L. pneumophila<\/jats:italic>\n            strains that secrete HGA are not wholly immune to its effects: low-density bacteria are strongly inhibited by HGA, whereas high-density cells are tolerant. How do these bacteria tolerate HGA and avoid self-harm during interbacterial competition? Here, we find that HGA toxicity occurs via the production of toxic hydroperoxides, and multiple factors facilitate high-density tolerance. First, HGA becomes fully toxic only after &gt;1 h of oxidation. While this manifests as a delay in killing within well-mixed liquid cultures, in a biofilm environment, this could provide time for HGA to diffuse away before becoming toxic. Second, HGA generates quantities of hydroperoxides that can be collectively scavenged by high-density, but not low-density, cells. Third, high-density cells produce one or more secreted factors that are transiently protective from HGA. In combination, we propose that the bacteria are able to deploy HGA to generate a pool of reactive oxygen species surrounding their own biofilms while maintaining non-toxic conditions within them. Overall, these findings help to explain how broadly toxic molecules can be used as inter-bacterial weapons. They also provide insights about why some of our current decontamination methods to control\n            <jats:italic>L. pneumophila<\/jats:italic>\n            are ineffective, leading to recurrent disease outbreaks.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Before environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted antimicrobials. We previously discovered that the bacterium\n              <jats:italic>Legionella pneumophila<\/jats:italic>\n              , the causative agent of Legionnaires\u2019 disease, can compete with other microbes via a secreted molecule called HGA. Curiously,\n              <jats:italic>L. pneumophila<\/jats:italic>\n              strains that produce HGA is not wholly immune to its toxicity, making it a mystery how these bacteria can withstand the \u201cfriendly fire\u201d of potentially self-targeting antimicrobials during inter-bacterial battles. Here, we identify several strategies that allow the high-density bacterial populations that secrete HGA to tolerate its effects. Our study clarifies how HGA works. It also points to some explanations of why it is difficult to disinfect\n              <jats:italic>L. pneumophila<\/jats:italic>\n              from the built environment and prevent disease outbreaks.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01207-23","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T13:00:49Z","timestamp":1695214849000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>L. pneumophila<\/i>\n            resists its self-harming metabolite HGA via secreted factors and collective peroxide scavenging"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-9211","authenticated-orcid":false,"given":"Mische","family":"Holland","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle N.","family":"Farinella","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Cruz-Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madelyn I.","family":"Laubscher","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darian A.","family":"Doakes","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California Berkeley , Berkeley, California, 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