Hijacking host cell vesicular transport: New insights into the nutrient acquisition mechanism of Chlamydia

Figures & data

Table 1. The role of host vesicular and non-vesicular transport pathway regulators in the nutrient acquisition process of Chlamydia..

Transport regulator	Family	Transport pathway	Inc or effector of Chlamydia	Role in trafficking during Chlamydia infection	Effector protein or cascade signaling pathway
Rab1	Rab GTPases	Vesicular trafficking	Cpn0585 [48]	Vesicular/membrane trafficking	OCRL1 [49]
Rab4	Rab GTPases	Vesicular trafficking	CT229 [20]	Rab GTPase-dependent CCV trafficking, iron and lipid delivery [20]	RUFY1 [50]
Rab6	Rab GTPases	Vesicular trafficking	CT622 [51]	Ceramide delivery [52]	BICD1 [53], OCRL1 [49]
Rab11	Rab GTPases	Vesicular trafficking	Cpn0585 [48]	Ceramide delivery [52]	FIP2 [54]
Rab14	Rab GTPases	Vesicular trafficking	unknown	lipids delivery [55]	FIP2 [56], PI3K/AKT/TBC1D4 signaling pathway [55]
Rab35	Rab GTPases	Vesicular trafficking	CT229 [20]	Rab GTPase-dependent CCV trafficking, iron and lipid delivery [20]	OCRL [20]
Rab39a/b	Rab GTPases	Vesicular trafficking	unknown	Multivesicular body (MVB) delivery [57]	–
ARF1	ARF GTPases	Vesicular trafficking	IncA(CT813)/CTL0184/InaC [58]	Modulates microtubules and Golgi dynamics [58], sphingomyelin delivery [59]	GBF1 [59]
VAMP3	SNAREs	Vesicular trafficking	IncF, IncG, CT442, CT449, and CT813 [60]	Promote membrane fusion [60]	–
VAMP4	SNAREs	Vesicular trafficking	unknown	Sphingomyelin delivery [61]	–
SNAP-23, Syntaxin 4	SNAREs	Vesicular trafficking	IncA (CT813) [62]	Regulate lipid droplet homeostasis [62]	–
SNX5/6	SNX family	Vesicular trafficking	IncE (CT116) [63]	Endosomal trafficking [63], CI-M6PR trafficking [64]	–
CERT	Lipid transfer proteins	Non-vesicular trafficking	IncD [65]	Transport ceramide from ER to Golgi [65]	–

Figure 1. Chlamydia hijacks host vesicular and non-vesicular trafficking pathways to acquire nutrients during infection. Inclusion serves as the interface that mediates the interaction between chlamydia and host cells. A series of effector proteins, including inclusion membrane proteins (incs) and T3SS effectors, interact with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), ADP-ribosylating factors (ARFs), and Rab GTPases, relocating from fragmented golgi mini-stacks, multivesicular bodies, endoplasmic reticulum, and endosome to acquire nutrients such as sphingomyelin, cholesterol, iron, cation-independent mannose 6-phosphate receptors (CI-M6PR), and transferrin. In addition, chlamydia hijacks host cell non-vesicular transport through incs–CERT interaction to obtain ceramide. Some elements in the figure have been sourced from the SMART database (https://smart.servier.com).

Figure 2. The role of Rab effector proteins and cascade signaling pathways is central to disrupting vesicular transport during chlamydia infection. chlamydia interacts with Rab effectors such as OCRL1, RUFY1, BICD1, and FIP2 to hijack Rab-mediated nutrient transport, redirecting lipid and iron delivery, which are crucial for the development and reproduction of its offspring. Furthermore, chlamydia infection induces AKT phosphorylation and recruits phosphorylated AKT to the inclusion membrane, thus phosphorylating and inactivating TBC1D4. Subsequently, the inactivated TBC1D4 activates Rab14 in a membrane-associated GTP-bound state. Therefore, vesicles marked by Rab14 that contain sphingolipids are redirected toward the inclusion. Elements in the figure are sourced from the SMART database (https://smart.servier.com).

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Data Availability statement

Data availability was not applicable to this study. No new datasets were generated in this study and the data cited in this review were obtained from published articles.