Disulfide Bonding Within Components of the Chlamydia Type III Secretion Apparatus Correlates with Development

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2011 Oct 18

PMID 22001510

Citations 12

Authors

H J Betts-Hampikian

K A Fields

Affiliations

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Abstract

Chlamydia spp. exhibit a unique biphasic developmental cycle whereby infectious elementary bodies (EBs) invade host epithelial cells and differentiate into noninfectious, metabolically active reticulate bodies (RBs). EBs posses a unique outer envelope where rigidity is achieved by disulfide bonding among cysteine-rich envelope-associated proteins. Conversely, these disulfide bonds become reduced in RBs to accommodate vegetative growth, thereby linking the redox status of cysteine-rich envelope proteins with progression of the developmental cycle. We investigated the potential role of disulfide bonding within the chlamydial type III secretion system (T3SS), since activity of this system is also closely linked to development. We focused on structural components of the T3S apparatus that contain an unusually high number of cysteine residues compared to orthologs in other secretion systems. Nonreducing SDS-PAGE revealed that EB-localized apparatus proteins such as CdsF, CdsD, and CdsC form higher-order complexes mediated by disulfide bonding. The most dramatic alterations were detected for the needle protein CdsF. Significantly, disulfide bonding patterns shifted during differentiation of developmental forms and were completely reduced in RBs. Furthermore, at later time points during infection following RB to EB conversion, we found that CdsF is reoxidized into higher-order complexes. Overall, we conclude that the redox status of specific T3SS apparatus proteins is intimately linked to the developmental cycle and constitutes a newly appreciated aspect of functionally significant alterations within proteins of the chlamydial envelope.

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References

Caldwell H, Kromhout J, Schachter J . Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1981; 31(3):1161-76. PMC: 351439. DOI: 10.1128/iai.31.3.1161-1176.1981. View

Turano C, Coppari S, Altieri F, Ferraro A . Proteins of the PDI family: unpredicted non-ER locations and functions. J Cell Physiol. 2002; 193(2):154-63. DOI: 10.1002/jcp.10172. View

Fields K, Hackstadt T . Evidence for the secretion of Chlamydia trachomatis CopN by a type III secretion mechanism. Mol Microbiol. 2000; 38(5):1048-60. DOI: 10.1046/j.1365-2958.2000.02212.x. View

Newhall 5th W . Biosynthesis and disulfide cross-linking of outer membrane components during the growth cycle of Chlamydia trachomatis. Infect Immun. 1987; 55(1):162-8. PMC: 260295. DOI: 10.1128/iai.55.1.162-168.1987. View

Peters J, Wilson D, Myers G, Timms P, Bavoil P . Type III secretion à la Chlamydia. Trends Microbiol. 2007; 15(6):241-51. DOI: 10.1016/j.tim.2007.04.005. View

Miki T, Okada N, Danbara H . Two periplasmic disulfide oxidoreductases, DsbA and SrgA, target outer membrane protein SpiA, a component of the Salmonella pathogenicity island 2 type III secretion system. J Biol Chem. 2004; 279(33):34631-42. DOI: 10.1074/jbc.M402760200. View

Valdivia R . Chlamydia effector proteins and new insights into chlamydial cellular microbiology. Curr Opin Microbiol. 2008; 11(1):53-9. DOI: 10.1016/j.mib.2008.01.003. View

Conant C, Stephens R . Chlamydia attachment to mammalian cells requires protein disulfide isomerase. Cell Microbiol. 2006; 9(1):222-32. DOI: 10.1111/j.1462-5822.2006.00783.x. View

Lazarev V, Borisenko G, Shkarupeta M, Demina I, Serebryakova M, Galyamina M . The role of intracellular glutathione in the progression of Chlamydia trachomatis infection. Free Radic Biol Med. 2010; 49(12):1947-55. DOI: 10.1016/j.freeradbiomed.2010.09.024. View

10.

AbdelRahman Y, Belland R . The chlamydial developmental cycle. FEMS Microbiol Rev. 2005; 29(5):949-59. DOI: 10.1016/j.femsre.2005.03.002. View

11.

Hatch T, Allan I, PEARCE J . Structural and polypeptide differences between envelopes of infective and reproductive life cycle forms of Chlamydia spp. J Bacteriol. 1984; 157(1):13-20. PMC: 215122. DOI: 10.1128/jb.157.1.13-20.1984. View

12.

Sardinia L, Segal E, Ganem D . Developmental regulation of the cysteine-rich outer-membrane proteins of murine Chlamydia trachomatis. J Gen Microbiol. 1988; 134(4):997-1004. DOI: 10.1099/00221287-134-4-997. View

13.

Torruellas J, Jackson M, Pennock J, Plano G . The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion. Mol Microbiol. 2005; 57(6):1719-33. DOI: 10.1111/j.1365-2958.2005.04790.x. View

14.

Hower S, Wolf K, Fields K . Evidence that CT694 is a novel Chlamydia trachomatis T3S substrate capable of functioning during invasion or early cycle development. Mol Microbiol. 2009; 72(6):1423-37. PMC: 2997736. DOI: 10.1111/j.1365-2958.2009.06732.x. View

15.

Bavoil P, Ohlin A, Schachter J . Role of disulfide bonding in outer membrane structure and permeability in Chlamydia trachomatis. Infect Immun. 1984; 44(2):479-85. PMC: 263545. DOI: 10.1128/iai.44.2.479-485.1984. View

16.

Betts H, Twiggs L, Sal M, Wyrick P, Fields K . Bioinformatic and biochemical evidence for the identification of the type III secretion system needle protein of Chlamydia trachomatis. J Bacteriol. 2008; 190(5):1680-90. PMC: 2258694. DOI: 10.1128/JB.01671-07. View

17.

Everett K, Hatch T . Architecture of the cell envelope of Chlamydia psittaci 6BC. J Bacteriol. 1995; 177(4):877-82. PMC: 176678. DOI: 10.1128/jb.177.4.877-882.1995. View

18.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

19.

Baehr W, Zhang Y, Joseph T, Su H, Nano F, Everett K . Mapping antigenic domains expressed by Chlamydia trachomatis major outer membrane protein genes. Proc Natl Acad Sci U S A. 1988; 85(11):4000-4. PMC: 280348. DOI: 10.1073/pnas.85.11.4000. View

20.

Yen T, Pal S, de la Maza L . Characterization of the disulfide bonds and free cysteine residues of the Chlamydia trachomatis mouse pneumonitis major outer membrane protein. Biochemistry. 2005; 44(16):6250-6. DOI: 10.1021/bi047775v. View