Francisella tularensis regulates the expression of the amino acid transporter SLC1A5 in infected THP-1 human monocytes.
Francisella tularensis, a Gram-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 Francisella intracellular multiplication in human monocyte cytoplasm is associated with a post-translational modification of a eukaryotic amino acid transporter.
INSERM U1002, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. monique.barel@inserm.fr
Monique
M
Barel
Karin
K
Meibom
Iharilalao
I
Dubail
Joaquin
J
Botella
Alain
A
Charbit
D026962:Amino Acid Transport System ASC / Q000096:biosynthesis*; D026905:Amino Acid Transport Systems; D001419:Bacteria; D002460:Cell Line; D005603:Francisella; D005604:Francisella tularensis / Q000254:growth & development / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000382:microbiology*; D015854:Up-Regulation
D026962:Amino Acid Transport System ASC; D026905:Amino Acid Transport Systems; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human