Identification of Functional Candidates amongst Hypothetical Proteins of Treponema pallidum ssp. pallidum

Abstract

Syphilis is a globally occurring venereal disease, and its infection is propagated through sexual contact. The causative agent of syphilis, Treponema pallidum ssp. pallidum, a Gram-negative sphirochaete, is an obligate human parasite. Genome of T. pallidum ssp. pallidum SS14 strain (RefSeq NC_010741.1) encodes 1,027 proteins, of which 444 proteins are known as hypothetical proteins (HPs), i.e., proteins of unknown functions. Here, we performed functional annotation of HPs of T. pallidum ssp. pallidum using various database, domain architecture predictors, protein function annotators and clustering tools. We have analyzed the sequences of 444 HPs of T. pallidum ssp. pallidum and subsequently predicted the function of 207 HPs with a high level of confidence. However, functions of 237 HPs are predicted with less accuracy. We found various enzymes, transporters, binding proteins in the annotated group of HPs that may be possible molecular targets, facilitating for the survival of pathogen. Our comprehensive analysis helps to understand the mechanism of pathogenesis to provide many novel potential therapeutic interventions.

Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen

“…Although the genomic sequence confirmed that T. pallidum depends upon its host for virtually all of its nutritional requirements 18 , it did not yield obvious, untried solutions to the cultivation problem 35 . A contemporary bioinformatics-based analysis of the possible functions of the more than 400 ‘hypothetical’ proteins encoded in the T. pallidum genome 40 may inform future attempts. Recent recognition of the importance of riboflavin uptake and flavin utilization for spirochete metabolism and energy generation may be pertinent as well 41,42 .…”

“…The presence of this pathway in T. pallidum is, therefore, a potentially important discovery. According to bioinformatics, T. pallidum contains two diguanylate cyclases for synthesizing c-di-GMP (TP0172 and TP0981) 136 , three phosphodiesterases for degrading it (TP0764, TP0877, and TP0912), and a putative effector protein (TP0086), which contains a c-di-GMP-binding PilZ domain 40,136 .…”

Functional Insight into Putative Conserved Proteins of Rickettsia rickettsii and their Virulence Characterization

“…The previously formulated protocols were used for the characterization of the HPs in the genome of R. rickettsii [4, Md. Imtaiyaz Hassan [20][21][22] (illustrated in Fig. 1).…”

The continuing threat of syphilis in pregnancy

“…As an example, the genome of T. Pallidum spp. pallidum has been sequenced and 1087 genes are present [22]. These encode for 1027 proteins, of which about 550 have had their function defined.…”

“…First, identification of protein function may lead to the development of effective new antibiotics. Second, these proteins may be useful in developing targeted vaccines for syphilis [22]. Third, investigation of proteins may lead to improved serodiagnosis of syphilis [23 & ].…”