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In direct contrast, <jats:italic>Mycoplasma alligatoris<\/jats:italic> elicits a fulminant, multisystem disease in the natural host, <jats:italic>Alligator mississippiensis<\/jats:italic> (American alligator). The goals of the study were to better understand the disease in the natural host and to determine if the invertebrate model <jats:italic>G. mellonella<\/jats:italic> could serve as a surrogate alternate host. The survival of alligators infected intratracheally was dose dependent (<jats:italic>p<\/jats:italic> = 0.0003), ranging from no mortality (10<jats:sup>2<\/jats:sup> CFU) to 100% mortality (10<jats:sup>8<\/jats:sup>\u2009CFU), with 60% mortality at the 10<jats:sup>4<\/jats:sup> and 10<jats:sup>5<\/jats:sup>\u2009CFU infectious dose. Microbial load in blood, joints, and brain was dose dependent, regardless of whether alligators were infected intratracheally or intravenously (<jats:italic>p<\/jats:italic>\u2009 &lt; 0.002). Weight loss was similarly impacted (<jats:italic>p<\/jats:italic>\u2009 &lt; 0.001). Experimental infection of the invertebrate <jats:italic>Galleria mellonella<\/jats:italic> mirrored the result in the natural host. In a dose response infection study, both larval survival curves and successful pupation curves were significantly different (<jats:italic>p<\/jats:italic> \u2264 0.0001) and dose dependent. Infected insects did not emerge as moths (<jats:italic>p<\/jats:italic>\u2009 &lt; 0.0001). Here, we describe the first study investigating <jats:italic>G. mellonella<\/jats:italic> as a surrogate model to assess the pathogenic potential of <jats:italic>M. alligatoris<\/jats:italic>. <jats:italic>G. mellonella<\/jats:italic> survival was dose dependent and impacted life stage outcome.<\/jats:p>","DOI":"10.1155\/2024\/3009838","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T03:20:06Z","timestamp":1711164006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Galleria mellonella<\/i> Invertebrate Model Mirrors the Pathogenic Potential of <i>Mycoplasma alligatoris<\/i> within the Natural Host"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5393-5649","authenticated-orcid":false,"given":"Alexandra 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