Emergence of Novel Chlamydia trachomatis Sequence Types among Chlamydia Patients in the Republic of Belarus.

Chlamydia trachomatis (CT) is a major cause of sexually transmitted diseases worldwide. The multilocus sequence typing (MLST) of clinical samples from random heterosexual chlamydia patients who were either asymptomatic or reported clinical manifestations of genital chlamydiosis (n = 63) in each of the seven major regions of the Republic of Belarus in 2017-2018 revealed 12 different CT sequence types (STs). We found seven known STs, ST4, ST6, ST9, ST13, ST38, ST95 and ST110, and five novel variants, namely ST271-ST275, which have not been detected elsewhere thus far. The ST4 variant was predominant (27/63, 42.9%) and detected in six out of seven regions. The two most common STs, ST9 and ST13, were regularly seen in four out of seven regions. In contrast, the remaining STs, ST6, ST38, ST95, ST110, and novel STs271-275, surfaced randomly in different parts of the country. The emergence of novel STs was registered in two regions, namely Minsk (ST271 and ST275) and Brest (ST271, ST272, ST273, and ST274). All the STs of detected CT strains were clustered into two Groups, I and III, which are characteristic of CT urogenital strains. No STs typical for Group II, specific to the LGV strains, were revealed. Our study contributes to better understanding the genetic diversity and molecular evolution of CT, one of the most important pathogens in public health worldwide.

Synthesis of erythrodiol C-ring derivatives and their activity against Chlamydia trachomatis.

To develop new potential agents against Chlamydia trachomatis among oleanane type triterpenoids the synthesis, spectral and X-ray analysis as well as antimicrobial screening of C-12 oxygen and nitrogen derivatives of erythrodiol is presented. The reduction of methyl 3ß-acetoxy-12-oxo-oleanoate with LiAlH4 led to isomeric erythrodiol 12ß- and 12α-hydroxy-derivatives, their stereochemistry with respect to the position of hydroxyl-group at C-12 was determined based on the multiplets splitting patterns, the magnitude of the spin-spin interaction, and NOESY interactions. Methyl 3ß-acetoxy-12-oxo-oleanoate was transformed to 12E-hydroxyimino- and 12E-methoxyimino-derivatives by the interaction with NH2OH∙HCl or CH3ONH2∙HCl, respectively. By Beckmann rearrangement with SOCl2 in dioxane 12E-oxime was converted to C-lactame and its following reduction with LiAlH4 in THF or dioxane led to erythrodiol C-azepanone or C-azepane derivatives. The structure 3-O,12-N-bis-acetyl-derivative of C-azepane-erythrodiol was confirmed by the single crystal X-ray analysis. Erythrodiol 12ß-hydroxy- and C-azepane derivatives were found to be lead compounds with significant activity against C. trachomatis with MIC 1.56 and 3.125 µg/mL. Molecular docking was employed to suggest potential binding interaction, the tested compounds are likely to act as Cdu1 protein inhibitors while 12ß-hydroxy-erythrodiol exhibited the highest affinity towards this respective target protein. These results indicated that C-ring oxygen and nitrogen erythrodiol derivatives might be considered for further research in the design of antibacterial agents against Chlamydia trachomatis.