The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis

Abstract

Chlamydia trachomatis, an obligate intracellular pathogen, grows inside of a vacuole, termed the inclusion. Within the inclusion, the organisms differentiate from the infectious elementary body (EB) into the reticulate body (RB). The RB communicates with the host cell through the inclusion membrane to obtain the nutrients necessary to divide, thus expanding the chlamydial population. At late time points within the developmental cycle, the RBs respond to unknown molecular signals to redifferentiate into infectious EBs to perpetuate the infection cycle. One strategy for Chlamydia to obtain necessary nutrients and metabolites from the host is to intercept host vesicular trafficking pathways. In this study we demonstrate that a trans-Golgi soluble N-ethylmaleimide–sensitive factor attachment protein (SNARE), syntaxin 10, and/or syntaxin 10-associated Golgi elements colocalize with the chlamydial inclusion. We hypothesized that Chlamydia utilizes the molecular machinery of syntaxin 10 at the inclusion membrane to intercept specific vesicular trafficking pathways in order to create and maintain an optimal intra-inclusion environment. To test this hypothesis, we used siRNA knockdown of syntaxin 10 to examine the impact of the loss of syntaxin 10 on chlamydial growth and development. Our results demonstrate that loss of syntaxin 10 leads to defects in normal chlamydial maturation including: variable inclusion size with fewer chlamydial organisms per inclusion, fewer infectious progeny, and delayed or halted RB-EB differentiation. These defects in chlamydial development correlate with an overabundance of NBD-lipid retained by inclusions cultured in syntaxin 10 knockdown cells. Overall, loss of syntaxin 10 at the inclusion membrane negatively affects Chlamydia. Understanding host machinery involved in maintaining an optimal inclusion environment to support chlamydial growth and development is critical toward understanding the molecular signals involved in successful progression through the chlamydial developmental cycle.

The cellular ceramide transport protein CERT promotesChlamydia psittaciinfection and controls bacterial sphingolipid uptake

“…Although sphingolipid accumulation in CERT‐KO cells differed between C. psittaci and C. trachomatis , CERT is essential for normal development of both species. Previous studies have shown that an imbalanced transport of nutrients including sphingolipids to the C. trachomatis inclusion had negative effects on the bacterial development (Lucas, Ouellette, Kabeiseman, Cichos, & Rucks, ; Ouellette & Carabeo, ). It remains to be determined how CERT controls sphingolipid acquisition during C. psittaci infections and how an increase in sphingolipids results a less infectious progeny formation in this species.…”

Chlamydia cell biology and pathogenesis

“…2b). These include the trans -Golgi SNARE proteins syntaxin 6 (STX6) 58,59 and STX10 (REF. 60), vesicle-associated membrane protein 4 (VAMP4), a STX6 binding partner 61 , and GS15 (also known as BET1L) 62 , which regulates the acquisition of nutrients from the Golgi exocytic pathway.…”

Epoxyeicosatrienoic acid ameliorates cerebral ischemia-reperfusion injury by inhibiting inflammatory factors and pannexin-1

“…Increased expression levels of PLA2 may induce genetic expression of COX-2 for numerous inflammation-stimulating factors, including lipopolysaccharide, IL-1, TNF, epidermal growth factor α and platelet activating factor (21), and increase levels of PGE2, prostacyclin and PGE1 at inflammatory sites. A positive association between COX-2 mRNA and PGE2 levels at inflammatory sites and severity of inflammation has been verified in numerous experiments (22). At present, PGE2 is considered as an important mediator of inflammation.…”