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Native flagellin does not protect mice against an experimental Proteus mirabilis ascending urinary tract infection and neutralizes the protective effect of MrpA fimbrial protein

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Abstract

Proteus mirabilis expresses several virulence factors including MR/P fimbriae and flagella. Bacterial flagellin has frequently shown interesting adjuvant and protective properties in vaccine formulations. However, native P. mirabilis flagellin has not been analyzed so far. Native P. mirabilis flagellin was evaluated as a protective antigen and as an adjuvant in co-immunizations with MrpA (structural subunit of MR/P fimbriae) using an ascending UTI model in the mouse. Four groups of mice were intranasally treated with either MrpA, native flagellin, both proteins and PBS. Urine and blood samples were collected before and after immunization for specific antibodies determination. Cytokine production was assessed in immunized mice splenocytes cultures. Mice were challenged with P. mirabilis, and bacteria quantified in kidneys and bladders. MrpA immunization induced serum and urine specific anti-MrpA antibodies while MrpA coadministered with native flagellin did not. None of the animals developed significant anti-flagellin antibodies. Only MrpA-immunized mice showed a significant decrease of P. mirabilis in bladders and kidneys. Instead, infection levels in MrpA-flagellin or flagellin-treated mice showed no significant differences with the control group. IL-10 was significantly induced in splenocytes of mice that received native flagellin or MrpA-flagellin. Native P. mirabilis flagellin did not protect mice against an ascending UTI. Moreover, it showed an immunomodulatory effect, neutralizing the protective role of MrpA. P. mirabilis flagellin exhibits particular immunological properties compared to other bacterial flagellins.

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Acknowledgments

This study was funded by ANII-FCE-2007_226. P. Scavone received a doctoral fellowship from ANII-BE-POS_2009_602.

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Authors and Affiliations

  1. Department of Microbiology, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia, 3318, CP 11600, Montevideo, Uruguay

    Paola Scavone, Ana Umpiérrez & Pablo Zunino

  2. Department of Biotechnology, Facultad de Medicina, Instituto de Higiene, UdelaR, Av. A. Navarro, 3051, CP 11600, Montevideo, Uruguay

    Analía Rial & José A. Chabalgoity

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  1. Paola Scavone
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  2. Ana Umpiérrez
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  4. José A. Chabalgoity
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  5. Pablo Zunino
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Correspondence to Paola Scavone.

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Scavone, P., Umpiérrez, A., Rial, A. et al. Native flagellin does not protect mice against an experimental Proteus mirabilis ascending urinary tract infection and neutralizes the protective effect of MrpA fimbrial protein. Antonie van Leeuwenhoek 105, 1139–1148 (2014). https://doi.org/10.1007/s10482-014-0175-7

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