{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:10:55Z","timestamp":1780805455197,"version":"3.54.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Melioidosis is caused by <jats:italic>Burkholderia pseudomallei<\/jats:italic>, an opportunistic Gram-negative pathogen that inhabits soil and water in tropical and subtropical regions. <jats:italic>B. pseudomallei<\/jats:italic> infections often occur following contact with contaminated water or soil or by inhalation of contaminated dust and water droplets. There is limited knowledge about how <jats:italic>B. pseudomallei<\/jats:italic> is able to survive in harsh environmental conditions and compete with the microbes that inhabit these niches. Previous research demonstrated that 3-methyl-2-alkylquinolones (MAQs), and their corresponding <jats:italic>N<\/jats:italic>-oxides (MAQNOs), are produced by <jats:italic>B. pseudomallei<\/jats:italic> and provide a competitive advantage when grown in the presence of Gram-positive bacteria. In this study, 39 Gram-negative environmental bacteria in the <jats:italic>Pseudomonadota<\/jats:italic> and <jats:italic>Bacteroidota<\/jats:italic> phyla were isolated and characterized. Intriguingly, <jats:italic>B. pseudomallei<\/jats:italic> inhibited 71% of bacteria in the phylum <jats:italic>Bacteroidota<\/jats:italic> in zone of inhibition and coculture competition assays, but no <jats:italic>Pseudomonadota<\/jats:italic> isolates were similarly inhibited. Transposon mutagenesis was utilized to identify <jats:italic>B. pseudomallei<\/jats:italic> genes required for the inhibition of <jats:italic>Sphingobacterium<\/jats:italic> sp. ST4, a representative member of the <jats:italic>Bacteroidota<\/jats:italic>. Three mutations mapped to <jats:italic>hmqA-G<\/jats:italic>, the locus encoding 2-alkylquinolone derivatives, and two mutations were identified in <jats:italic>scmR<\/jats:italic>, a gene encoding a quorum-sensing controlled LysR-type transcriptional regulator. <jats:italic>B. pseudomallei<\/jats:italic> strains with deletion mutations in <jats:italic>hmqD<\/jats:italic> and <jats:italic>scmR<\/jats:italic> were unable to produce 2-alkylquinolone derivatives or inhibit <jats:italic>Bacteroidota<\/jats:italic> isolates in competition assays. RAW264.7 murine macrophage cells were infected with <jats:italic>B. pseudomallei<\/jats:italic> 1026b and 1026b <jats:italic>\u0394hmqD<\/jats:italic> and there was a 94-fold reduction in the number of intracellular 1026b <jats:italic>\u0394hmqD<\/jats:italic> bacteria relative to 1026b. The 50% lethal dose (LD<jats:sub>50<\/jats:sub>) of 1026b and 1026b <jats:italic>\u0394hmqD<\/jats:italic> in BALB\/c mice was determined to be 3 x 10<jats:sup>5<\/jats:sup> colony forming units (CFU) and &amp;gt; 1 x 10<jats:sup>6<\/jats:sup> CFU, respectively. Taken together, the results indicate that the products of the <jats:italic>B. pseudomallei hmqA-G<\/jats:italic> locus are important for intracellular replication in murine macrophages, virulence in a mouse model of melioidosis, and competition with bacteria that utilize naphthoquinones for aerobic respiration.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1474033","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:52:10Z","timestamp":1728881530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Burkholderia pseudomallei produces 2-alkylquinolone derivatives important for host virulence and competition with bacteria that employ naphthoquinones for aerobic respiration"],"prefix":"10.3389","volume":"15","author":[{"given":"Sherry","family":"Mou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriia","family":"Savchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Filz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"B\u00f6ttcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2020.148259","article-title":"Advances in bacterial pathways for the biosynthesis of ubiquinone.","volume":"1861","author":"Abby","year":"2020","journal-title":"Biochim. 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