Open AccessF rancisella tularensis regulates the expression of the amino acid transporter SLC1A5 in infected THP ‐1 human monocytes
Author(s) -
Barel Monique,
Meibom Karin,
Dubail Iharilalao,
Botella Joaquin,
Charbit Alain
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01837.x
Subject(s) - francisella tularensis , tularemia , biology , intracellular , intracellular parasite , microbiology and biotechnology , francisella , cytoplasm , phagosome , amino acid transporter , monocyte , downregulation and upregulation , macrophage , transporter , virulence , biochemistry , gene , in vitro , immunology
Summary F rancisella tularensis , a G ram‐negative bacterium that causes the disease tularemia in a large number of animal species, is thought to reside preferentially within macrophages in vivo . F . tularensis has developed mechanisms to rapidly escape from the phagosome into the cytoplasm of infected cells, a habitat with a rich supply of nutrients, ideal for multiplication. SLC1A5 is a neutral amino acid transporter expressed by human cells, which serves, along with SLC7A5 to equilibrate cytoplasmic amino acid pools. We herein analysed whether SLC1A5 was involved in F . tularensis intracellular multiplication. We demonstrate that expression of SLC1A5 is specifically upregulated by F . tularensis in infected THP ‐1 human monocytes. Furthermore, we show that SLC1A5 downregulation decreases intracellular bacterial multiplication, supporting the involvement of SLC1A5 in F . tularensis infection. Notably, after entry of F . tularensis into cells and during the whole infection, the highly glycosylated form of SLC1A5 was deglycosylated only by bacteria capable of cytosolic multiplication. These data suggest that intracellular replication of F . tularensis depends on the function of host cell SLC1A5 . Our results are the first, which show that F rancisella intracellular multiplication in human monocyte cytoplasm is associated with a post‐translational modification of a eukaryotic amino acid transporter.