Capsid protein Vp1 from chlamydiaphage φCPG1 effectively alleviates cytotoxicity induced by Chlamydia trachomatis

Ren,Jie; Guo,Yuanli; Shao,Lili; Liu,Yuanjun; Liu,Quanzhong

doi:10.3892/etm.2018.6629

Capsid protein Vp1 from chlamydiaphage φCPG1 effectively alleviates cytotoxicity induced by Chlamydia trachomatis

Authors:
- Jie Ren
- Yuanli Guo
- Lili Shao
- Yuanjun Liu
- Quanzhong Liu
View Affiliations

Affiliations: Dermatology and Venereology Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Dermatology Department, Tianjin Union Medical Center, Tianjin 300121, P.R. China
Published online on: August 20, 2018 https://doi.org/10.3892/etm.2018.6629
Pages: 3286-3292
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections. C. trachomatis genital infection may lead to pelvic inflammatory disease, ectopic pregnancy and tubal infertility, which are major public health problems. However, the pathogenic mechanisms of this bacterium remain unclear, and the efficacy of clinical therapeutics is unsatisfactory. In the current study, whether Vp1 can alleviate the cytotoxicity induced by Chlamydia trachomatis infection was investigated. C. trachomatis was pre‑treated with BSA or purified Vp1 protein and used to infect HeLa cells. It was observed that Vp1 significantly inhibited the infectivity of C. trachomatis in cell cultures. In addition, the Vp1 pretreatment reduced the chlamydial Hsp60 protein levels and decreased the C. trachomatis inclusion number. The Vp1 pretreatment also prevented C. trachomatis‑induced cytotoxicity in host cells. Furthermore, the chlamydial suppression of host cell proapoptotic p53 protein and the induction of antiapoptotic cIAP‑2 and Mcl‑1 gene expression were reversed by the Vp1 pretreatment. These observations suggest that Vp1 has a clear inhibitory effect on C. trachomatis growth in vitro.

View Figures

View References

1	Centers for Disease Control and Prevention: sexually transmitted diseases surveillance 2016. U.S. Department of Health and Human Services. Atlanta, GA: 2017, https://www.cdc.gov/std/October 25–2017
2	Yue XL, Gong XD, Teng F, Jiang N, Li J, Men PX and Wang J: Epidemiologic features of genital Chlamydia trachomatis infection in national sexually transmitted disease surveillance sites in China from 2008 to 2015. Chin J Dermatol. 49:308–313. 2016.(In Chinese).
3	Darville T: Recognition and treatment of chlamydial infections from birth to adolescence. Adv Exp Med Biol. 764:109–122. 2013. View Article : Google Scholar : PubMed/NCBI
4	Haggerty CL, Gottlieb SL, Taylor BD, Low N, Xu F and Ness RB: Risk of sequelae after Chlamydia trachomatis genital infection in women. J Infect Dis. 201 Suppl 2:S134–S155. 2010. View Article : Google Scholar : PubMed/NCBI
5	Brown HM, Knowlton AE and Grieshaber SS: Chlamydial infection induces host cytokinesis failure at abscission. Cell Microbiol. 14:1554–1567. 2012. View Article : Google Scholar : PubMed/NCBI
6	Carabeo RA, Grieshaber SS, Fischer E and Hackstadt T: Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells. Infect Immun. 70:3793–3803. 2002. View Article : Google Scholar : PubMed/NCBI
7	Kumar Y and Valdivia RH: Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds. Cell Host Microbe. 4:159–169. 2008. View Article : Google Scholar : PubMed/NCBI
8	Garner SA, Everson JS, Lambden PR, Fane BA and Clarke IN: Isolation, molecular characterisation and genome sequence of a bacteriophage (Chp3) from Chlamydophila pecorum. Virus Genes. 28:207–214. 2004. View Article : Google Scholar : PubMed/NCBI
9	Hoestgaard-Jensen K, Christiansen G, Honoré B and Birkelund S: Influence of the Chlamydia pneumoniae AR39 bacteriophage φCPAR39 on chlamydial inclusion morphology. FEMS Immunol Med Microbiol. 62:148–156. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hsia R, Ohayon H, Gounon P, Dautry-Varsat A and Bavoil PM: Phage infection of the obligate intracellular bacterium, Chlamydia psittaci strain guinea pig inclusion conjunctivitis. Microbes Infect. 2:761–772. 2000. View Article : Google Scholar : PubMed/NCBI
11	Liu BL, Everson JS, Fane B, Giannikopoulou P, Vretou E, Lambden PR and Clarke IN: Molecular characterization of a bacteriophage (Chp2) from Chlamydia psittaci. J Virol. 74:3464–3469. 2000. View Article : Google Scholar : PubMed/NCBI
12	Storey CC, Lusher M and Richmond SJ: Analysis of the complete nucleotide sequence of Chp1, a phage which infects avian Chlamydia psittaci. J Gen Virol. 70:3381–3390. 1989. View Article : Google Scholar : PubMed/NCBI
13	Hsia RC, Ting LM and Bavoil PM: Microvirus of chlamydia psittaci strain guinea pig inclusion conjunctivitis: Isolation and molecular characterization. Microbiology. 146:1651–1660. 2000. View Article : Google Scholar : PubMed/NCBI
14	Sait M, Livingstone M, Graham R, Inglis NF, Wheelhouse N and Longbottom D: Identification, sequencing and molecular analysis of Chp4, a novel chlamydiaphage of Chlamydophila abortus belonging to the family Microviridae. J Gen Virol. 92:1733–1737. 2011. View Article : Google Scholar : PubMed/NCBI
15	Guo Y, Guo R, Zhou Q, Sun C, Zhang X, Liu Y and Liu Q: Chlamydiaphage φCPG1 capsid protein Vp1 inhibits Chlamydia trachomatis growth via the mitogen-activated protein kinase pathway. Viruses. 8:992016. View Article : Google Scholar : PubMed/NCBI
16	Wang S, Guo R, Guo YL, Shao LL, Liu Y, Wei SJ, Liu YJ and Liu QZ: Biological effects of chlamydiaphage phiCPG1 capsid protein Vp1 on Chlamydia trachomatis in vitro and in vivo. J Huazhong Univ Sci Technolog Med Sci. 37:115–121. 2017. View Article : Google Scholar : PubMed/NCBI
17	Ma J, Sun Y, Sun C, Zhou Q, Qi M, Kong J, Wang J, Liu Y and Liu Q: Identification of proteins differentially expressed by Chlamydia trachomatis treated with chlamydiaphage capsid protein VP1 during intracellular growth. Arch Microbiol. 199:1121–1131. 2017. View Article : Google Scholar : PubMed/NCBI
18	González E, Rother M, Kerr MC, Al-Zeer MA, Abu-Lubad M, Kessler M, Brinkmann V, Loewer A and Meyer TF: Chlamydia infection depends on a functional MDM2-p53 axis. Nat Commun. 5:52012014. View Article : Google Scholar : PubMed/NCBI
19	Siegl C, Prusty BK, Karunakaran K, Wischhusen J and Rudel T: Tumor suppressor p53 alters host cell metabolism to limit Chlamydia trachomatis infection. Cell Rep. 9:918–929. 2014. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Hafner LM, Wilson DP and Timms P: Development status and future prospects for a vaccine against Chlamydia trachomatis infection. Vaccine. 32:1563–1571. 2014. View Article : Google Scholar : PubMed/NCBI
22	Bastidas RJ, Elwell CA, Engel JN and Valdivia RH: Chlamydial intracellular survival strategies. Cold Spring Harb Perspect Med. 3:a0102562013. View Article : Google Scholar : PubMed/NCBI
23	Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, Greenberg AH and Zhong G: Inhibition of apoptosis in chlamydia-infected cells: Blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med. 187:487–496. 1998. View Article : Google Scholar : PubMed/NCBI
24	Galluzzi L, Brenner C, Morselli E, Touat Z and Kroemer G: Viral control of mitochondrial apoptosis. PLoS Pathog. 4:e10000182008. View Article : Google Scholar : PubMed/NCBI
25	Heuer D, Rejman Lipinski A, Machuy N, Karlas A, Wehrens A, Siedler F, Brinkmann V and Meyer TF: Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction. Nature. 457:731–735. 2009. View Article : Google Scholar : PubMed/NCBI
26	Ying S, Pettengill M, Latham ER, Walch A, Ojcius DM and Häcker G: Premature apoptosis of Chlamydia-infected cells disrupts chlamydial development. J Infect Dis. 198:1536–1544. 2008. View Article : Google Scholar : PubMed/NCBI
27	Rajalingam K, Sharma M, Lohmann C, Oswald M, Thieck O, Froelich CJ and Rudel T: Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells. PLoS One. 3:e31022008. View Article : Google Scholar : PubMed/NCBI
28	Rajalingam K, Sharma M, Paland N, Hurwitz R, Thieck O, Oswald M, Machuy N and Rudel T: IAP-IAP complexes required for apoptosis resistance of C. trachomatis-infected cells. PLoS Pathog. 2:e1142006. View Article : Google Scholar : PubMed/NCBI
29	Śliwa-Dominiak J, Suszyńska E, Pawlikowska M and Deptuła W: Chlamydia bacteriophages. Arch Microbiol. 195:765–771. 2013. View Article : Google Scholar : PubMed/NCBI
30	Liu Y, Sun YN, Yao W, Li Y, Li Z, Wei J and Liu QZ: The detection of the binding protein of chlamydiaphage phiCPGl capsid protein Vpl on chlamydial outer membrane of serotype D. Chin J Infect Dis. 32:583–586. 2012.(In Chinese).