Affiliation:
1. Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-901 85, Sweden
2. Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, Washington 98195
Abstract
ABSTRACT
The
Francisella tularensis
live vaccine strain (LVS), in contrast to its
iglC
mutant, replicates in the cytoplasm of macrophages. We studied the outcome of infection of the murine macrophagelike cell line J774A.1 with LVS and with
iglC
,
iglD
, and
mglA
mutants, the latter of which is deficient in a global regulator. Compared to LVS, all of the mutants showed impaired intracellular replication up to 72 h, and the number of the
mglA
mutant bacteria even decreased. Colocalization with LAMP-1 was significantly increased for all mutants compared to LVS, indicating an impaired ability to escape into the cytoplasm. A lysosomal acidity-dependent dye accumulated in approximately 40% of the vacuoles containing mutant bacteria but not at all in vacuoles containing LVS. Preactivation of the macrophages with gamma interferon inhibited the intracellular growth of all strains and significantly increased acidification of phagosomes containing the mutants, but it only slightly increased the LAMP-1 colocalization. The intracellular replication and phagosomal escape of the
iglC
and
iglD
mutants were restored by complementation in
trans
. In conclusion, the IglC, IglD, and MglA proteins each directly or indirectly critically contribute to the virulence of
F. tularensis
LVS, including its intracellular replication, cytoplasmic escape, and inhibition of acidification of the phagosomes.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
104 articles.
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