Oxidoreductase disulfide bond proteins DsbA and DsbB form an active redox pair in Chlamydia trachomatis, a bacterium with disulfide dependent infection and development

PLoS One. 2019 Sep 19;14(9):e0222595. doi: 10.1371/journal.pone.0222595. eCollection 2019.

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium with a distinctive biphasic developmental cycle that alternates between two distinct cell types; the extracellular infectious elementary body (EB) and the intracellular replicating reticulate body (RB). Members of the genus Chlamydia are dependent on the formation and degradation of protein disulfide bonds. Moreover, disulfide cross-linking of EB envelope proteins is critical for the infection phase of the developmental cycle. We have identified in C. trachomatis a homologue of the Disulfide Bond forming membrane protein Escherichia coli (E. coli) DsbB (hereafter named CtDsbB) and-using recombinant purified proteins-demonstrated that it is the redox partner of the previously characterised periplasmic oxidase C. trachomatis Disulfide Bond protein A (CtDsbA). CtDsbA protein was detected in C. trachomatis inclusion vacuoles at 20 h post infection, with more detected at 32 and similar levels at 44 h post infection as the developmental cycle proceeds. As a redox pair, CtDsbA and CtDsbB largely resemble their homologous counterparts in E. coli; CtDsbA is directly oxidised by CtDsbB, in a reaction in which both periplasmic cysteine pairs of CtDsbB are required for complete activity. In our hands, this reaction is slow relative to that observed for E. coli equivalents, although this may reflect a non-native expression system and use of a surrogate quinone cofactor. CtDsbA has a second non-catalytic disulfide bond, which has a small stabilising effect on the protein's thermal stability, but which does not appear to influence the interaction of CtDsbA with its partner protein CtDsbB. Expression of CtDsbA during the RB replicative phase and during RB to EB differentiation coincided with the oxidation of the chlamydial outer membrane complex (COMC). Together with our demonstration of an active redox pairing, our findings suggest a potential role for CtDsbA and CtDsbB in the critical disulfide bond formation step in the highly regulated development cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Chlamydia trachomatis / metabolism*
  • Disulfides / metabolism*
  • Escherichia coli / metabolism
  • Membrane Proteins / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / metabolism*
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Domains / physiology
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Proteins
  • Disulfides
  • DsbB protein, Bacteria
  • Membrane Proteins
  • Recombinant Proteins
  • Oxidoreductases
  • Protein Disulfide-Isomerases

Grants and funding

RMM, MH and GP are supported by a Ramaciotti (www.perpetual.com.au/ramaciotti) Health Investment Grant (2017HIG0094) awarded to RMM. RMM and SC were also supported by a NHMRC (www.nhmrc.gov.au) Project Grant (1099151) awarded to JLM. GP is further supported by a Griffith University Postgraduate Research Scholarship and a Griffith University International Postgraduate Research Scholarship (www.griffith.edu.au/research-study/scholarships). SC was further supported by a UQI Tuition Fee Award (www.scholarships.uq.edu.au/). WMH is supported by University Technology Sydney (www.uts.edu.au) Faculty of Science Staff Development Funding and NS is supported by a UTS Doctoral Scholarship. This work is also supported by a NHMRC Project Grant (1144046) awarded to JLM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.