Cholesterol dependent Bordetella pertussis attachment to host cells is not linked to the bacterial virulent state

LAMBERTI, YANINA; PEREZ VIDAKOVICS, M LAURA; RODRÍGUEZ, M. EUGENIA

Pinamar, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB). X Congreso de la Panamerican association for Biochemistry and Molecular Biology (PABMB); 2005

Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

B. pertussis (Bp) is a re-emerging human respiratory pathogen whose infectious process is not fully understood precluding the design of effective vaccines. The nature of bacterial attachment to host cells is often the key event in the outcome of the infection. The so-called adhesins of Bp , like Filamentous Hemagglutinin (FHA) or Cya, found critical for the binding activity of FHA, are expressed only in the virulent phase. However, we found the avirulent phase of Bp, regarded as important during early and late stages of infection, to be able to attach to respiratory cells. In vivo studies confirmed these findings. We here investigated the role of the cholesterol, a molecule involved in other persistent infectious processes, in the virulence-independent interaction of Bp with the host cells. Human respiratory epithelial cells (A549) treated with and without cyclodextrin were incubated with virulent and avirulent Bp wild type strain or two isogenic mutants deficient of either FHA or Cya. The synthesis of cholesterol de novo was inhibited by the addition of lovastatin. The results showed that the lack of cholesterol led to a significant decrease in bacterial attachment (about 75%) which proved independent of the virulent state or presence of FHA or Cya. Attachment inhibition studies with growing concentrations of cholesterol confirmed its involvement in the bacterial binding. Internalization and survival studies showed a relevant role of cholesterol in the intracellular trafficking. Whether this is a mechanism of attachment during transmission when bacteria is not yet expressing FHA or a way by which bacteria entering in the host in an avirulent state are directed to different compartments remains to be investigated