The pore-forming major surface protein (Msp) and the major protease complex (CTLP) of Treponema denticola ATCC 35405 have been implicated in periodontal pathogenicity. Previous studies showed thatmutations in msp or the prcA-prtP loci resulted in unexpected effects on expression of Msp and CTLP complex proteins. One msp mutant (MHE) produced no Msp and apparently normal levels of CTLP proteins, while another msp mutant (MPE) produced a small amount of truncated monomeric Msp and no CTLP proteins. Strains mutated in the locus encoding CTLP (prcA-prtP) produced no protease and little or no Msp. Objective: The present study was designed to further investigate the relationship between Msp and CTLP. Method: Transcription of the genes encoding Msp and CTLP was monitored in parent strain (ATCC 35405) and isogenic mutants PNE (prcA), CCE (prtP), CKE (prcA-prtP), MHE (msp) and MPE (msp). Total RNA was prepared from cultures harvested throughout the growth phase (optical density at 600 nm of 0.1, 0.2 and 0.3) and at stationary phase (5th day). Quantitative real-time RT-PCR was performed using 16S rRNA as an internal control. Results: We detected no major differences between the parent strain and msp mutants MHE and MPE in prcA or prtP transcription during active growth. Transcription of msp in the CTLP mutants was reduced during active growth. Transcription of msp upstream of the mutation site in MHE was drastically reduced at all time points. Conclusions: Presence or absence of Msp protein had no apparent effect on transcription of prcA and prtP. The lack of CTLP protease activity in strain MPE is thus likely due to post-transcriptional events. The observed differences between parent and mutant strains in msp transcription levels suggest that both Msp and CTLP proteins may be involved in regulating or modulating msp transcription. Supported by NIH grant DE13565.