Global Transcriptomic Analysis During Murine Pneumonia Infection Reveals New Virulence Factors in Acinetobacter baumannii
2020
Alvarez-Fraga, Laura | Martínez-Guitián, Marta | Vázquez-Ucha, Juan, C | Conde-Pérez, Kelly | Vallejo, Juan, A | Perina, Alejandra | Bou, Germán | Poza, Margarita | Beceiro, Alejandro | Instituto de Investigación Biomédica de A Coruña [La Corogne, Espagne] (INIBIC) ; A Coruña University Hospital [La Corogne, Espagne] | Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre ; The University of Queensland (UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]) | AllGenetics & Biology SL, A Coruña | This work was supported by Instituto de Salud Carlos III (PI15/00860 and PI18/00501 to G. B. and PI14/00059 and PI17/01482 to A. B. and M. P.); Axencia Galega de Innovacion- Consellería de Economía, Emprego e Industria (IN607A 2016/22 to G. B); Spanish Network for Research in Infectious Diseases and European Development Regional Fund (REIPI RD16/0016/006 and FI18/00315 to J. C. V.-U); M. M.-G. was supported by the Spanish Society of Clinical Microbiology and Infectious Diseases (Clara Roy grant); and K. C.-P. was supported by the Spanish Association Against Cancer.
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Show more [+] Less [-]English. Background. Infections caused by multidrug-resistant pathogens such as Acinetobacter baumannii constitute a major health problem worldwide. In this study we present a global in vivo transcriptomic analysis of A. baumannii isolated from the lungs of mice with pneumonia infection.Methods. Mice were infected with A. baumannii ATCC 17978 and AbH12O-A2 strains and the total bacterial RNA were analyzed by RNA sequencing. Lists of differentially expressed genes were obtained and 14 of them were selected for gene deletion and further analysis.Results. Transcriptomic analysis revealed a specific gene expression profile in A. baumannii during lung infection with upregulation of genes involved in iron acquisition and host invasion. Mutant strains lacking feoA, mtnN, yfgC, basB, hisF, oatA, and bfnL showed a significant loss of virulence in murine pneumonia. A decrease in biofilm formation, adherence to human epithelial cells, and growth rate was observed in selected mutants.Conclusions. This study provides an insight into A. baumannii gene expression profile during murine pneumonia infection. Data revealed that 7 in vivo upregulated genes were involved in virulence and could be considered new therapeutic targets.
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