Flavoridin inhibits Yersinia enterocolitica uptake into fibronectin-adherent HeLa cells.
In this study, three structurally distinct disintegrins (flavoridin, echistatin, kistrin) were used as molecular probes to further characterize the molecular mechanisms underlying Yersinia enterocolitica infection of host cells. The activity of the three disintegrins on Y. enterocolitica uptake into fibronectin-adherent HeLa cells was evaluated at disintegrin doses which were non-cytotoxic and unable to induce cell detachment. Flavoridin resulted to be the most effective in inhibiting bacterial entry into host cells; echistatin was almost 50% less effective than flavoridin, whereas kistrin was definitely inactive. Our results suggest that alpha(5)beta(1) integrin receptor, which binds flavoridin with higher affinity than the other two disintegrins, plays a major role in Y. enterocolitica uptake into HeLa cells. Furthermore, flavoridin binding to this integrin prevented the disruption of the functional complex FAK-Cas, which occurs in the Y. enterocolitica uptake process.
Scibelli
Antonio
A
Dipartimento di Patologia e Sanità Animale, Italy.
Matteoli
Gianluca
G
Roperto
Sante
S
Alimenti
Elena
E
Dipineto
Ludovico
L
Pavone
Luigi Michele
LM
Della Morte
Rossella
R
Menna
Lucia Francesca
LF
Fioretti
Alessandro
A
Staiano
Norma
N
D001422:Bacterial Adhesion / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D019483:Disintegrins / Q000494:pharmacology*; D005353:Fibronectins; D051417:Focal Adhesion Kinase 1 / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects* / Q000382:microbiology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D015335:Molecular Probes; D010455:Peptides / Q000494:pharmacology*; D015008:Yersinia enterocolitica / Q000187:drug effects* / Q000472:pathogenicity
D003435:Crotalid Venoms; D019483:Disintegrins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D036341:Intercellular Signaling Peptides and Proteins; D015335:Molecular Probes; D010455:Peptides; C069044:flavoridin protein, Trimeresurus; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human