Evidence of Bacteroides fragilis Protection from Bartonella henselae-Induced Damage

Linda Sommese, Chiara Pagliuca, Bice Avallone, Rossana Ippolito, Amelia Casamassimi, Valerio Costa, Roberta Colicchio, Raimondo Cerciello, Maria D'Armiento, Margherita Scarpato, Alfonso Giovane, Gabiria Pastore, Teresa Infante, Alfredo Ciccodicola, Carmela Fiorito, Francesco Paolo D'Armiento, Paola Salvatore, Claudio Napoli

Research output: Contribution to journalArticle

Abstract

Bartonella henselae is able to internalize endothelial progenitor cells (EPCs), which are resistant to the infection of other common pathogens. Bacteroides fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects from experimental colitis induced by Helicobacter hepaticus through the polysaccharide A (PSA). The aim of our study was to establish: 1) whether B. fragilis colonization could protect from B. henselae infection; if this event may have beneficial effects on EPCs, vascular system and tissues. Our in vitro results establish for the first time that B. fragilis can internalize EPCs and competes with B. henselae during coinfection. We observed a marked activation of the inflammatory response by Real-time PCR and ELISA in coinfected cells compared to B. henselae-infected cells (63 vs 23 up-regulated genes), and after EPCs infection with mutant B. fragilis ΔPSA (≅90% up-regulated genes) compared to B. fragilis. Interestingly, in a mouse model of coinfection, morphological and ultrastructural analyses by hematoxylin-eosin staining and electron microscopy on murine tissues revealed that damages induced by B. henselae can be prevented in the coinfection with B. fragilis but not with its mutant B. fragilis ΔPSA. Moreover, immunohistochemistry analysis with anti-Bartonella showed that the number of positive cells per field decreased of at least 50% in the liver (20±4 vs 50±8), aorta (5±1 vs 10±2) and spleen (25±3 vs 40±6) sections of mice coinfected compared to mice infected only with B. henselae. This decrease was less evident in the coinfection with ΔPSA strain (35±6 in the liver, 5±1 in the aorta and 30±5 in the spleen). Finally, B. fragilis colonization was also able to restore the EPC decrease observed in mice infected with B. henselae (0.65 vs 0.06 media). Thus, our data establish that B. fragilis colonization is able to prevent B. henselae damages through PSA.

Original languageEnglish
Article numbere49653
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - Nov 15 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Sommese, L., Pagliuca, C., Avallone, B., Ippolito, R., Casamassimi, A., Costa, V., Colicchio, R., Cerciello, R., D'Armiento, M., Scarpato, M., Giovane, A., Pastore, G., Infante, T., Ciccodicola, A., Fiorito, C., D'Armiento, F. P., Salvatore, P., & Napoli, C. (2012). Evidence of Bacteroides fragilis Protection from Bartonella henselae-Induced Damage. PLoS One, 7(11), [e49653]. https://doi.org/10.1371/journal.pone.0049653