The role of intracellular glutathione in the progression of Chlamydia trachomatis infection.
The productive internalization in the host cell of Chlamydia trachomatis elementary bodies and their infectivity depends on the degree of reduction of disulfide bonds in the outer envelope of the elementary body. We have hypothesized that the reducing agent may be intracellular glutathione (GSH). Three approaches were used to modulate the intracellular GSH concentration: (1) treatment of cells with buthionine sulfoximine, which causes irreversible inhibition of GSH biosynthesis; (2) hydrogen peroxide-induced oxidation of GSH by intracellular glutathione peroxidases; and (3) treatment of cells with N-acetyl-l-cysteine (NAC), a precursor of glutathione. In the first two cases, we observed a four- to sixfold inhibition of C. trachomatis infection, whereas in NAC-treated cells we detected an increase in the size of chlamydial inclusions. Using a proteomics approach, we showed that the inhibition of chlamydial infection does not combine with alterations in protein expression patterns after cell treatment. These results suggest that GSH plays a key role in the reduction of disulfide bonds in the C. trachomatis outer envelope at an initial stage of the infection.
Lazarev
Vassili N
VN
Research Institute for Physico-Chemical Medicine, Moscow, Russia. lazar0@mail.ru
Borisenko
Grigory G
GG
Shkarupeta
Marina M
MM
Demina
Irina A
IA
Serebryakova
Marina V
MV
Galyamina
Maria A
MA
Levitskiy
Sergey A
SA
Govorun
Vadim M
VM
D000111:Acetylcysteine / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism; D020543:Proteome / Q000378:metabolism
D020543:Proteome; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine