{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:41:32Z","timestamp":1774039292930,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011491","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000}}],"reference-count":113,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2010841"],"award-info":[{"award-number":["2010841"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Ministry of Defence"},{"DOI":"10.13039\/100010418","name":"Defence Science and Technology Laboratory","doi-asserted-by":"publisher","award":["DSTLX-1000051512"],"award-info":[{"award-number":["DSTLX-1000051512"]}],"id":[{"id":"10.13039\/100010418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000830","name":"North Atlantic Treaty Organization","doi-asserted-by":"publisher","award":["SPS 984835"],"award-info":[{"award-number":["SPS 984835"]}],"id":[{"id":"10.13039\/501100000830","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 630"],"award-info":[{"award-number":["SFB 630"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020593","name":"DMTC","doi-asserted-by":"publisher","award":["10.44 and 10.133"],"award-info":[{"award-number":["10.44 and 10.133"]}],"id":[{"id":"10.13039\/501100020593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Coxiella burnetii<\/jats:italic> is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl <jats:italic>cis<\/jats:italic>-<jats:italic>trans<\/jats:italic> isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> pathogenesis has not been investigated. This study demonstrates that <jats:italic>Cb<\/jats:italic>Mip is likely to be an essential protein in <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic>. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against <jats:italic>Cb<\/jats:italic>Mip. These compounds were found to significantly inhibit intracellular replication of <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> sensitivity assays validating that Mip inhibition increases the sensitivity of <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> to oxidative stress. In addition, SF235 and AN296 were effective <jats:italic>in vivo<\/jats:italic> and significantly improved the survival of <jats:italic>Galleria mellonella<\/jats:italic> infected with <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic>. These results suggest that unlike in other bacteria, Mip in <jats:italic>C<\/jats:italic>. <jats:italic>burnetii<\/jats:italic> is required for replication and that the development of more potent inhibitors against <jats:italic>Cb<\/jats:italic>Mip is warranted and offer potential as novel therapeutics against this pathogen.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011491","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T17:29:01Z","timestamp":1688405341000},"page":"e1011491","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis"],"prefix":"10.1371","volume":"19","author":[{"given":"Aleksandra W.","family":"Debowski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M.","family":"Bzdyl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nichollas E.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher H.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jua","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily A.","family":"Kibble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen Ai","family":"Khoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas J.","family":"Scheuplein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela M.","family":"Seibel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Lohr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgie","family":"Metters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles S.","family":"Bond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isobel H.","family":"Norville","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Stubbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Harmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Holzgrabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley J.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-8499","authenticated-orcid":true,"given":"Mitali","family":"Sarkar-Tyson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ppat.1011491.ref001","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1186\/1471-2334-13-488","article-title":"Human dose response relation for airborne exposure to Coxiella burnetii.","volume":"13","author":"RJ Brooke","year":"2013","journal-title":"BMC Infect. 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