Affiliation:
1. Institute of Microbiology, ETH-Zurich, CH-8093, Zurich, Switzerland
Abstract
ABSTRACT
The food-borne pathogen
Salmonella enterica
serovar Typhimurium invades mammalian epithelial cells. This multistep process comprises bacterial binding to the host cell, activation of the
Salmonella
type three secretion system 1 (T1), injection of effector proteins, triggering of host cell actin rearrangements, and
S
. Typhimurium entry. While the latter steps are well understood, much less is known about the initial binding step. Earlier work had implicated adhesins (but not T1) or T1 (but not other adhesins). We have studied here the
Salmonella
virulence factors mediating
S
. Typhimurium binding to HeLa cells. Using an automated microscopy assay and isogenic
S
. Typhimurium mutants, we analyzed the role of T1 and of several known adhesins (Fim, Pef, Lpf, Agf, and Shd) in host cell binding. In wild-type
S
. Typhimurium, host cell binding was mostly attributable to T1. However, in the absence of T1, Fim (but not Pef, Lpf, Agf, and Shd) also mediated HeLa cell binding. Furthermore, in the absence of T1 and type I fimbriae (Fim), we still observed residual binding, pointing toward at least one additional, unidentified binding mechanism. Dissociation experiments established that T1-mediated binding was irreversible (“docking”), while Fim-mediated binding was reversible (“reversible adhesion”). Finally, we show that noninvasive bacteria docking via T1 or adhering via Fim can efficiently invade HeLa cells, if actin rearrangements are triggered
in trans
by a wild-type
S
. Typhimurium helper strain. Our data show that binding to HeLa cells is mediated by at least two different mechanisms and that both can lead to invasion if actin rearrangements are triggered.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
73 articles.
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