Abstract:Chlamydia is a kind of prokaryotic microorganism which may cause various diseases in human and animals. The pathogenesis of Chlamydia is complex, mainly due to its direct pathogenic effect and the infection-induced immunopathological damage on host cells, but the existing evidences cannot fully explain the processe. Nowadays, the development in techniques of molecular biology offer convenience to research of chlamydial pathogenesis. This paper summarized chlamydial current situation, challenges and the directions in the future work based on its pathogenisis, from the aspects which include pathogenic substances, pathogenesis research strategies and biological significance.
刘娜, 周洲. 衣原体致病机制的研究策略及挑战[J]. 中国人兽共患病学报, 2019, 35(6): 552-557.
LIU Na,ZHOU Zhou. Challenges and research strategies for the pathogenesis of Chlamydia. Chinese Journal of Zoonoses, 2019, 35(6): 552-557.
[1] Bachmann NL, Polkinghorne A, Timms P. Chlamydia genomics: providing novel insights into chlamydial biology[J]. Trends Microbiol, 2014, 22(8): 464-472. DOI: 10.1016/j.tim.2014.04.013 [2] Wiesenfeld HC. Screening for Chlamydia trachomatis infections in women[J]. N Engl J Med,2017,376(8): 765-773. DOI: 10.1056/NEJMcp1412935 [3] Kuo CC, Jackson LA, Campbell LA, et al. Chlamydia pneumoniae (TWAR)[J]. Clin Microbiol Rev,1995,8(4): 451-461. DOI: 10.1016/0020-2452(96)85764-2 [4] Su H, Raymond L, Rockey DD, et al. A recombinant Chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells[J]. Proc Natl Acad Sci U S A,1996, 93(20): 11143-11148. DOI: 10.1073/pnas.93.20.11143 [5] Gervassi AL, Grabstein KH, Probst P, et al. Human CD8+ T cells recognize the 60-kDa cysteine-rich outer membrane protein from Chlamydia trachomatis[J]. J Immunol, 2004, 173(11): 6905-6913. DOI: 10.4049/jimmunol.173.11.6905 [6] Mlleken K, Schmidt E, Hegemann JH. Members of the Pmp protein family of Chlamydia pneumoniae mediate adhesion to human cells via short repetitive peptide motifs[J]. Mol Microbiol, 2010, 78(4): 1004-1017. DOI: 10.1111/j.1365-2958.2010.07386.x [7] Weber MM, Lam JL, Dooley CA, et al. Absence of specific Chlamydia trachomatis inclusion membrane proteins triggers premature inclusion membrane lysis and host cell death[J]. Cell Rep, 2017, 19(7): 1406-1417. DOI: 10.1016/j.celrep.2017.04.058 [8] Jorgensen I, Bednar MM, Amin V, et al. The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence[J]. Cell Host Microbe, 2011, 10(1): 21-32. DOI: 10.1016/j.chom.2011.06.008 [9] Lad SP, Li J, da SCJ, et al. Cleavage of p65/RelA of the NF-kappaB pathway by Chlamydia[J]. Proc Natl Acad Sci U S A, 2007,104(8): 2933-2938. DOI: 10.1073/pnas.0608393104 [10] Marsh JW, Lott WB, Tyndall JD, et al. Proteolytic activation of Chlamydia trachomatis HTRA is mediated by PDZ1 domain interactions with protease domain loops L3 and LC and beta strand β5[J]. Cell Mol Biol Lett, 2013, 18(4): 522-537. DOI: 10.2478/s11658-013-0103-2 [11] Liu Y, Huang Y, Yang Z, et al. Plasmid-encoded Pgp3 is a major virulence factor for Chlamydia muridarum to induce hydrosalpinx in mice[J]. Infect Immun, 2014, 82(12): 5327-5335. DOI: 10.1128/IAI.02576-14 [12] Cortes C, Rzomp KA, Tvinnereim A, et al. Chlamydia pneumoniae inclusion membrane protein Cpn0585 interacts with multiple Rab GTPases[J]. Infect Immun,2007,75(12): 5586-5596. DOI: 10.1128/IAI.01020-07 [13] Muschiol S, Bailey L, Gylfe A, et al. A small-molecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis[J]. Proc Natl Acad Sci U S A, 2006, 103(39): 14566-14571. DOI: 10.1073/pnas.0606412103 [14] Murthy AK, Cong Y, Murphey C, et al. Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele[J]. Infect Immun, 2006, 74(12): 6722-6229. DOI: 10.1128/IAI.01119-06 [15] Thwaites TR, Pedrosa AT, Peacock TP, et al. Vinculin interacts with the Chlamydia effector TarP via a tripartite vinculin binding domain to mediate actin recruitment and assembly at the plasma membrane[J]. Front Cell Infect Microbiol, 2015, 5: 88-118. DOI: 10.3389/fcimb.2015.00088 [16] Nguyen BD, Cunningham D, Liang X, et al. Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis[J]. Proc Natl Acad Sci U S A,2011, 108(25): 10284-10289. DOI: 10.1073/pnas.1107478108 [17] Bas S, Neff L, Vuillet M, et al. The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14[J]. J Immunol,2008, 180(2): 1158-1168. DOI: 10.4049/jimmunol.180.2.1158 [18] Russell M, Darville T, Chandra-Kuntal K, et al. Infectivity acts as in vivo selection for maintenance of the chlamydial cryptic plasmid[J]. Infect Immun, 2011, 79(1): 98-107. DOI: 10.1128/IAI.01105-10 [19] Chen C, Zhou Z, Conrad T, et al. In vitro passage selects for Chlamydia muridarum with enhanced infectivity in cultured cells but attenuated pathogenicity in mouse upper genital tract[J]. Infect Immun, 2015, 83(5): 1881-1892. DOI: 10.1128/IAI.03158-14 [20] Kokes M, Dunn JD, Granek JA, et al. Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia[J]. Cell Host Microbe, 2015, 17(5): 716-725. DOI: 10.1016/j.chom.2015.03.014 [21] Kari L, Southern TR, Downey CJ, et al. Chlamydia trachomatis polymorphic membrane protein D is a virulence factor involved in early host-cell interactions[J]. Infect Immun,2014, 82(7): 2756-2762. DOI: 10.1128/iai.01686-14 [22] Snavely EA, Kokes M, Dunn JD, et al. Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches[J]. Pathog Dis, 2014,71(3): 336-351. DOI: 10.1111/2049-632X.12179 [23] Yang C, Kari L, Sturdevant GL, et al. Chlamydia trachomatis ChxR is a transcriptional regulator of virulence factors that function in in vivo host-pathogen interactions[J]. Pathog Dis, 2017,75(3): ftx035. DOI: 10.1093/femspd/ftx035 [24] Patton MJ, Chen CY, Yang C, et al. Plasmid negative regulation of CPAF expression is Pgp4 independent and restricted to invasive Chlamydia trachomatis biovars[J]. MBio, 2018, 9(1): e02164-e02181. DOI: 10.1128/mBio.02164-17 [25] Liechti G, Singh R, Rossi PL, et al. Chlamydia trachomatis dapF encodes a bifunctional enzyme capable of both d-Glutamate racemase and diaminopimelate epimerase activities[J]. MBio, 2018, 9(2): e00204-e00222. DOI: 10.1128/mBio.00204-18 [26] Wang Y, Liu Q, Chen D, et al. Chlamydial lipoproteins stimulate Toll-Like receptors 1/2 mediated inflammatory responses through MyD88-Dependent pathway[J]. Front Microbiol,2017(8): 78-97. DOI: 10.3389/fmicb.2017.00078 [27] Peters J, Onguri V, Nishimoto SK, et al. The Chlamydia trachomatis CT149 protein exhibits esterase activity in vitro and catalyzes cholesteryl ester hydrolysis when expressed in HeLa cells[J]. Microbes Infect, 2012, 14(13): 1196-1204. DOI: 10.1016/j.micinf.2012.07.020 [28] Vromman F, Perrinet S, Gehre L, et al. The DUF582 proteins of Chlamydia trachomatis bind to components of the ESCRT machinery, which is dispensable for bacterial growth in vitro[J]. Front Cell Infect Microbiol, 2016(6): 123-153. DOI: 10.3389/fcimb.2016.00123 [29] Demars R, Weinfurter J, Guex E, et al. Lateral gene transfer in vitro in the intracellular pathogen Chlamydia trachomatis[J]. J Bacteriol, 2007, 189(3): 991-1003. DOI: 10.1128/JB.00845-06 [30] Wang Y, Kahane S, Cutcliffe LT, et al. Development of a transformation system for Chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector[J]. PLoS Pathog, 2011, 7(9): e1002258. DOI: 10.1371/journal.ppat.1002258 [31] Agaisse H, Derré I. A C. trachomatis cloning vector and the generation of C. trachomatis strains expressing fluorescent proteins under the control of a C. trachomatis promoter[J]. PLoS One, 2013, 8(2): e57090. DOI: 10.1371/journal.pone.0057090 [32] Lei L, Chen J, Hou S, et al. Reduced live organism recovery and lack of hydrosalpinx in mice infected with plasmid-free Chlamydia muridarum[J]. Infect Immun, 2014, 82(3): 983-992. DOI: 10.1128/IAI.01543-13 [33] Huang Y, Zhang Q, Yang Z, et al. Plasmid-Encoded Pgp5 is a significant contributor to Chlamydia muridarum induction of hydrosalpinx[J]. PLoS One,2015, 10(4): e0124840. DOI: 10.1371/journal.pone.0124840 [34] Shao L, Zhang T, Melero J, et al. The genital tract virulence factor pGP3 is essential for Chlamydia muridarum colonization in the gastrointestinal tract[J]. Infect Immun, 2018, 86(1): 429-446 DOI: 10.1128/iai.00429-17 [35] Liu Y, Chen C, Gong S, et al. Transformation of Chlamydia muridarum reveals a role for Pgp5 in suppression of plasmid-dependent gene expression[J]. J Bacteriol, 2014, 196(5): 989-998. DOI: 10.1128/jb.01161-13 [36] Song L, Carlson JH, Whitmire WM, et al. Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence-associated genes[J]. Infect Immun, 2013, 81(3): 636-644. DOI: 10.1128/IAI.01305-12 [37] Johnson CM, Fisher DJ. Site-specific, insertional inactivation of incA in Chlamydia trachomatis using a group II intron[J]. PLoS One, 2013, 8(12): e83989. DOI: 10.1371/journal.pone.0083989
[38] Mueller KE, Wolf K, Fields KA. Gene deletion by fluorescence-reported allelic exchange mutagenesis in Chlamydia trachomatis[J]. MBio, 2016, 7(1): e01817-e01832. DOI: 10.1128/mBio.01817-15 [39] Ouellette SP. Feasibility of a conditional knockout system for Chlamydia based on CRISPR interference[J]. Front Cell Infect Microbiol,2018(8): 59-77. DOI: 10.3389/fcimb.2018.00059 [40] Mital J, Lutter EI, Barger AC, et al. Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1) [J]. Biochem Biophys Res Commun,2015,462(2): 165-170. DOI: 10.1016/j.bbrc.2015.04.116 [41] Hanson BR, Slepenkin A, Peterson EM, et al. Chlamydia trachomatis type III secretion proteins regulate transcription[J]. J Bacteriol, 2015, 197(20): 3238-3244. DOI: 10.1128/JB.00379-15 [42] Lorenzini E, Singer A, Singh B, et al. Structure and protein-protein interaction studies on Chlamydia trachomatis protein CT670 (YscO Homolog) [J]. J Bacteriol, 2010, 192(11): 2746-2756. DOI: 10.1128/JB.01479-09 [43] Zhao X, Li P, An K, et al. Chlamydia pneumoniae inclusion membrane protein Cpn0147 interacts with host protein CREB3[J]. PLoS One, 2017, 12(9): e0185593. DOI: 10.1371/journal.pone.0185593 [44] Pal S, Peterson EM, de la Maza LM. Susceptibility of mice to vaginal infection with Chlamydia trachomatis mouse pneumonitis is dependent on the age of the animal[J]. Infect Immun, 2001, 69(8): 5203-5206. DOI: 10.1128/IAI.69.8.5203-5206.2001 [45] De Clercq E, Kalmar I, Vanrompay D. Animal models for studying female genital tract infection with Chlamydia trachomatis[J]. Infect Immun, 2013, 81(9): 3060-3067. DOI: 10.1128/IAI.00357-13 [46] O’Connell CM, Ingalls RR, Andrews CW, et al. Plasmid-deficient Chlamydia muridarum fail to induce immune pathology and protect against oviduct disease[J]. J Immunol, 2007, 179(6): 4027-4034. DOI: 10.4049/jimmunol.179.6.4027