{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:19:52Z","timestamp":1775647192725,"version":"3.50.1"},"reference-count":26,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,12]]},"abstract":"<jats:p><jats:italic>Burkholderia pseudomallei<\/jats:italic> is the causative agent of melioidosis, a serious infection associated with high mortality and relapse. Current antimicrobial therapy using ceftazidime (CAZ) is often ineffective. Inhibitors of LpxC, the enzyme responsible for lipid A biosynthesis, have potential antimicrobial activity against several Gram-negative bacteria in vivo, but their activity against <jats:italic>B. pseudomallei<\/jats:italic> is unclear. Herein, we investigated the susceptibility of <jats:italic>B. pseudomallei<\/jats:italic> clinical isolates to LpxC-4, an LpxC inhibitor, and LpxC-4 in combination with CAZ. Time-kill assays for bactericidal activity were conducted for <jats:italic>B. pseudomallei<\/jats:italic> K96243, revealing growth inhibition and bactericidal effect at LpxC-4 concentrations of 2 \u03bcg\/mL and 4 \u03bcg\/mL, respectively. No significant synergistic effect was observed with the combination of LpxC-4 and CAZ. LpxC-4 susceptibility was tested on three groups of clinical isolates:1) CAZ- and trimethoprim\u2013sulfamethoxazole (SXT)\u2013susceptible (<jats:italic>N<\/jats:italic> = 71), 2) CAZ-resistant (<jats:italic>N<\/jats:italic> = 14), and 3) SXT-resistant (<jats:italic>N<\/jats:italic> = 23) isolates, by broth microdilution. The minimum concentration of LpxC-4 required to inhibit the growth of 90% of organisms was 2 \u03bcg\/mL for all isolates. The median minimum inhibitory concentration of both the CAZ\/SXT-susceptible and CAZ-resistant groups was 1 \u03bcg\/mL (interquartile range [IQR] = 1\u20132 \u03bcg\/mL), compared with 2 \u03bcg\/mL (IQR = 2\u20134 \u03bcg\/mL) for the SXT-resistant group. Cell morphology was observed after drug exposure by immunofluorescent staining, and a change from rod-shaped to cell wall\u2013defective spherical cells was observed in surviving bacteria. LpxC-4 is a potent bactericidal agent against <jats:italic>B. pseudomallei<\/jats:italic> and warrants further testing as a new antibiotic to treat melioidosis.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0858","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T07:00:22Z","timestamp":1493103622000},"page":"62-67","source":"Crossref","is-referenced-by-count":12,"title":["Susceptibility of Clinical Isolates of Burkholderia pseudomallei to a Lipid A Biosynthesis Inhibitor"],"prefix":"10.4269","volume":"97","author":[{"given":"Sineenart","family":"Sengyee","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natnaree","family":"Saiprom","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suporn","family":"Paksanont","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"},{"name":"Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanaporn","family":"Wuthiekanun","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"},{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"ref1","series-title":"N Engl J Med","first-page":"1035","article-title":"Melioidosis","volume":"367","author":"Wiersinga","year":"2012"},{"key":"ref2","series-title":"Nat Microbiol","first-page":"pii: 15008","article-title":"Predicted global distribution of and burden of melioidosis","volume":"1","author":"Limmathurotsakul","year":"2016"},{"key":"ref3","series-title":"Lancet","first-page":"807","article-title":"Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral 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