Francisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB/c Mice

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dc.contributor.authorPropst, Crystal N.
dc.contributor.authorPylypko, Stephanie L.
dc.contributor.authorBlower, Ryan J.
dc.contributor.authorAhmad, Saira
dc.contributor.authorMansoor, Mohammad
dc.contributor.authorvan Hoek, Monique L.
dc.date.accessioned2016-08-25T15:41:27Z
dc.date.available2016-08-25T15:41:27Z
dc.date.issued2016-05-24
dc.description.abstractFrancisella (F.) philomiragia is a Gram-negative bacterium with a preference for brackish environments that has been implicated in causing bacterial infections in near-drowning victims. The purpose of this study was to characterize the ability of F. philomiragia to infect cultured mammalian cells, a commonly used invertebrate model, and, finally, to characterize the ability of F. philomiragia to infect BALB/c mice via the pulmonary (intranasal) route of infection. This study shows that F. philomiragia infects J774A.1 murine macrophage cells, HepG2 cells and A549 human Type II alveolar epithelial cells. However, replication rates vary depending on strain at 24 h. F. philomiragia infection after 24 h was found to be cytotoxic in human U937 macrophage-like cells and J774A.1 cells. This is in contrast to the findings that F. philomiragia was non-cytotoxic to human hepatocellular carcinoma cells, HepG2 cells and A549 cells. Differential cytotoxicity is a point for further study. Here, it was demonstrated that F. philomiragia grown in host-adapted conditions (BHI, pH 6.8) is sensitive to levofloxacin but shows increased resistance to the human cathelicidin LL-37 and murine cathelicidin mCRAMP when compared to related the Francisella species, F. tularensis subsp. novicida and F. tularensis subsp. LVS. Previous findings that LL-37 is strongly upregulated in A549 cells following F. tularensis subsp. novicida infection suggest that the level of antimicrobial peptide expression is not sufficient in cells to eradicate the intracellular bacteria. Finally, this study demonstrates that F. philomiragia is lethal in two in vivo models; Galleria mellonella via hemocoel injection, with a LD50 of 1.8 × 103, and BALB/c mice by intranasal infection, with a LD50 of 3.45 × 103. In conclusion, F. philomiragia may be a useful model organism to study the genus Francisella, particularly for those researchers with interest in studying microbial ecology or environmental strains of Francisella. Additionally, the Biosafety level 2 status of F. philomiragia makes it an attractive model for virulence and pathogenesis studies.
dc.description.sponsorshipThis work was partially supported by funded from DTRA (HDTRA1-11-1-0054) to MvH, the U.S. Department of Homeland Security under Cooperative Agreement Number DHS 2010-ST-061-AG0002 (CP), and Virginia’s Commonwealth Health Research Board (APBJ/MvH). Animal studies were performed with support from the GMU Foundation. The authors gratefully acknowledge the Open Access Publishing Fund of George Mason University to support the publication of this article.
dc.identifier.citationPropst CN, Pylypko SL, Blower RJ, Ahmad S, Mansoor M and van Hoek ML (2016) Francisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB/c Mice. Front. Microbiol. 7:696. doi: 10.3389/fmicb.2016.00696
dc.identifier.doihttp://dx.doi.org/10.3389/fmicb.2016.00696
dc.identifier.urihttps://hdl.handle.net/1920/10345
dc.language.isoen_US
dc.publisherFrontiers
dc.subjectFrancisella philomiragia
dc.subjectMurine model
dc.subjectMammalian cells
dc.subjectGalleria mellonella
dc.subjectPulmonary infection
dc.subjectIntranasal
dc.titleFrancisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB/c Mice
dc.typeArticle

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