Genome-wide codon usage profiling of ocular infectiveChlamydia trachomatisserovars and drug target identification

Abstract

Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC. Similarly, relative synonymous codon usage also showed preference towards A/U ending codons. Parity Rule 2 analysis inferred unequal distribution of AT and GC, indicative of other unknown factors acting along with mutational pressure to influence codon usage bias (CUB). Moreover, absolute quantification of CUB also revealed lower bias across these serovars. The effect of natural selection on CUB was also confirmed by neutrality plot, reinforcing natural selection under mutational pressure turned to be a pivotal role in shaping the CUB in the strains studied. Correspondence analysis (COA) clarified that, C.t C/TW-3 to show a unique trend in codon usage variation. Host influence analysis on shaping the codon usage pattern also inferred some speculative relativity. In a nutshell, our finding suggests that mutational pressure is the dominating factor in shaping CUB in the strains studied, followed by natural selection. We also propose potential drug targets based on cumulative analysis of strand bias, CUB and human non-homologue screening.

PocketPipe: A computational pipeline for integrated Pocketome prediction and comparison

“…Computed aided drug design has become an indispensable part of Drug Discovery right from targeting microbes 9, 10 to disease conditions in humans. This poses a need for efficient open source based pipelines for efficient analysis.…”

Identification of potential drugs targeting L,L‐diaminopimelate aminotransferase of Chlamydia trachomatis: An integrative pharmacoinformatics approach

“…25 Hence, this L-Lysine biosynthetic pathways in bacteria and plants have been widely investigated by many groups for drug targeting because of their crucial role in synthesis of PG cell wall in most bacteria [26][27][28][29] and host nonhomology. 5 In this study, L,L-diaminopimelate aminotransferase of C.t (CtDAP-AT) was considered for drug targeting study, as this organism is solely dependent on this pathway for L-lysine synthesis.…”

“…The increase in drug resistance among this species indicates an urgent need for alternate and potential antibacterial targets to help combat the infections. 5,25 Molecular modeling and structural bioinformatics serves as powerful tool for studying intermolecular interactions and dynamic behavior of molecules in in silico simulated conditions. 33,34 The purpose of this study is to identify potential inhibitors targeting CtDAP-AT.…”

“…This enzymatic reaction is also common to all four DAP/lys anabolic variants, for the overall detailed enzymatic reaction, refer to Hudson et al and Alexander et al (2014) . Hence, this l ‐Lysine biosynthetic pathways in bacteria and plants have been widely investigated by many groups for drug targeting because of their crucial role in synthesis of PG cell wall in most bacteria and host nonhomology . In this study, L,L‐diaminopimelate aminotransferase of C.t (CtDAP‐AT) was considered for drug targeting study, as this organism is solely dependent on this pathway for l ‐lysine synthesis.…”

“…3,4 The antibiotics that are currently used for treating chlamydial infections target on 50S and 30S ribosomal subunits, DNA gyrase, and topoisomerase IV, which are generic to many of the microbes. 5 Recent studies show that C.t has developed a resistance to generic antibiotics such as Azhithromycin and tetracycline) 6,7 thus, posing a need for novel drug targets and combating methods.…”