Rab4b Promotes Cytolethal Distending Toxin from -Induced Cytotoxicity in PK-15 Cells

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2024 Sep 27

PMID 39330865

Authors

Yiwen Zhang

Zhen Yang

Ke Dai

Bangdi Hu

Shiyu Xu

Yu Wang

Li Lei

Senyan Du

Qin Zhao

Xiaobo Huang

Rui Wu

Qigui Yan

Yiping Wang

Sanjie Cao

Yiping Wen

Affiliations

Soon will be listed here.

Abstract

cytolethal distending toxin (CDT) can induce cell cycle arrest and apoptosis. Our laboratory's previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in CDT-induced cytotoxicity. This study investigated the probable involvement of Rab4b in the process. Our study used CRISPR/Cas9 technology to create a Rab4b-knockout cell line. The results showed greater resistance to CDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased CDT-induced cytotoxicity. Further immunoprecipitation study reveals that CDT may bind with Rab4b. In PK-15 cells, CDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, CDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for CDT-induced cytotoxicity in PK-15 cells.

References

Costa-Hurtado M, Barba-Vidal E, Maldonado J, Aragon V . Update on Glässer's disease: How to control the disease under restrictive use of antimicrobials. Vet Microbiol. 2020; 242:108595. DOI: 10.1016/j.vetmic.2020.108595. View

Yang Z, Zhang Y, Du S, Zhao Q, Huang X, Wu R . Upregulation of occludin by cytolethal distending toxin facilitates adhesion to respiratory tract cells. Infect Immun. 2023; 91(12):e0035123. PMC: 10715221. DOI: 10.1128/iai.00351-23. View

Chen H, Li L, Chen X, Yang M, Ye Y, Wang X . The mechanism of Jurkat cells apoptosis induced by Aggregatibacter actinomycetemcomitans cytolethal distending toxin. Apoptosis. 2017; 22(6):841-851. DOI: 10.1007/s10495-017-1357-3. View

Dixon S, Huynh M, Tamilselvam B, Spiegelman L, Son S, Eshraghi A . Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins. PLoS One. 2015; 10(11):e0143977. PMC: 4664275. DOI: 10.1371/journal.pone.0143977. View

Gerding D, Johnson S, Rupnik M, Aktories K . Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance. Gut Microbes. 2013; 5(1):15-27. PMC: 4049931. DOI: 10.4161/gmic.26854. View

Spano S, Galan J . Taking control: Hijacking of Rab GTPases by intracellular bacterial pathogens. Small GTPases. 2017; 9(1-2):182-191. PMC: 5902217. DOI: 10.1080/21541248.2017.1336192. View

Matangkasombut O, Wattanawaraporn R, Tsuruda K, Ohara M, Sugai M, Mongkolsuk S . Cytolethal distending toxin from Aggregatibacter actinomycetemcomitans induces DNA damage, S/G2 cell cycle arrest, and caspase- independent death in a Saccharomyces cerevisiae model. Infect Immun. 2009; 78(2):783-92. PMC: 2812194. DOI: 10.1128/IAI.00857-09. View

Shenker B, Boesze-Battaglia K, Scuron M, Walker L, Zekavat A, Dlakic M . The toxicity of the Aggregatibacter actinomycetemcomitans cytolethal distending toxin correlates with its phosphatidylinositol-3,4,5-triphosphate phosphatase activity. Cell Microbiol. 2015; 18(2):223-43. DOI: 10.1111/cmi.12497. View

Guerra L, Nemec K, Massey S, Tatulian S, Thelestam M, Frisan T . A novel mode of translocation for cytolethal distending toxin. Biochim Biophys Acta. 2009; 1793(3):489-95. PMC: 2647582. DOI: 10.1016/j.bbamcr.2008.11.017. View

10.

Pons B, Vignard J, Mirey G . Cytolethal Distending Toxin Subunit B: A Review of Structure-Function Relationship. Toxins (Basel). 2019; 11(10). PMC: 6832162. DOI: 10.3390/toxins11100595. View

11.

Brockmeier S, Loving C, Mullins M, Register K, Nicholson T, Wiseman B . Virulence, transmission, and heterologous protection of four isolates of Haemophilus parasuis. Clin Vaccine Immunol. 2013; 20(9):1466-72. PMC: 3889593. DOI: 10.1128/CVI.00168-13. View

12.

Wang Q, Chang X, Liu M, Lu Q, Zhu M, Lin H . Glaesserella parasuis serotype 4 HPS4-YC disrupts the integrity of the swine tracheal epithelial barrier and facilitates bacterial translocation. Vet Res. 2021; 52(1):135. PMC: 8529811. DOI: 10.1186/s13567-021-01005-w. View

13.

Taieb F, Petit C, Nougayrede J, Oswald E . The Enterobacterial Genotoxins: Cytolethal Distending Toxin and Colibactin. EcoSal Plus. 2016; 7(1). PMC: 11575708. DOI: 10.1128/ecosalplus.ESP-0008-2016. View

14.

Mohrmann K, Gerez L, Oorschot V, Klumperman J, van der Sluijs P . Rab4 function in membrane recycling from early endosomes depends on a membrane to cytoplasm cycle. J Biol Chem. 2002; 277(35):32029-35. DOI: 10.1074/jbc.M203064200. View

15.

Jordens I, Marsman M, Kuijl C, Neefjes J . Rab proteins, connecting transport and vesicle fusion. Traffic. 2005; 6(12):1070-7. DOI: 10.1111/j.1600-0854.2005.00336.x. View

16.

McCaffrey M, Bielli A, Cantalupo G, Mora S, Roberti V, Santillo M . Rab4 affects both recycling and degradative endosomal trafficking. FEBS Lett. 2001; 495(1-2):21-30. DOI: 10.1016/s0014-5793(01)02359-6. View

17.

Scuron M, Boesze-Battaglia K, Dlakic M, Shenker B . The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin. Front Cell Infect Microbiol. 2016; 6:168. PMC: 5136569. DOI: 10.3389/fcimb.2016.00168. View

18.

Huhn 3rd G, Sparkes C, Silva I, Reyes C, Perez G, Khondker F . Acid-induced disassembly of the Haemophilus ducreyi cytolethal distending toxin. Biochem Biophys Res Commun. 2022; 636(Pt 1):57-63. DOI: 10.1016/j.bbrc.2022.10.068. View

19.

Guerra L, Cortes-Bratti X, Guidi R, Frisan T . The biology of the cytolethal distending toxins. Toxins (Basel). 2011; 3(3):172-90. PMC: 3202825. DOI: 10.3390/toxins3030172. View

20.

Chen M, Chen Y, Fu R, Mao G, Liu S, Shen T . Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation. Infect Immun. 2020; 88(10). PMC: 7504948. DOI: 10.1128/IAI.00132-20. View