Genome-wide codon usage profiling of ocular infective Chlamydia trachomatis serovars and drug target identification

J Biomol Struct Dyn. 2018 Jun;36(8):1979-2003. doi: 10.1080/07391102.2017.1343685. Epub 2017 Jul 4.

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.

Keywords: Chlamydia trachomatis; codon usage; mutational bias; natural selection; neonatal conjunctivitis; trachoma.

MeSH terms

  • Algorithms
  • Base Composition / genetics
  • Chlamydia Infections / microbiology
  • Chlamydia trachomatis / genetics*
  • Chlamydia trachomatis / physiology
  • Codon / genetics*
  • Genome, Bacterial / genetics*
  • Genomics / methods*
  • Humans
  • Models, Genetic
  • Mutation
  • Selection, Genetic
  • Serogroup

Substances

  • Codon