Abstract: Leptospirosis is a resurgent infectious disease that has a vital impact on public health. It is caused by the widely dispersed zoonotic bacterium Leptospira interrogans. The enzyme heme oxygenase which is essential for both iron uptake and heme breakdown, is crucial to the pathogen's ability to survive and spread throughout the host. This study conducts a comparative in silico analysis of heme oxygenase protein from geographically diverse isolates of Leptospira interrogans to understand structural, functional, and evolutionary variations. Multiple sequence alignment and phylogenetic analysis of heme oxygenase proteins from geographically diverse regions spanning 15 countries revealed its mostly conserved nature with few unique amino acid substitutions. Among the substitutions few were observed to be non-conservative and charge altering amino acid substitutions like Phe84Ile, Asp102Asn, Asp181Asn, and Lys105Gln. These substitutions may affect enzyme stability, substrate binding affinity and active site conformation. A particular hotspot of mutation at Lys105Gln probably due adaptive evolution was also identified. Furthermore, evolutionary analysis revealed that heme oxygenase protein is mostly conserved as the isolates segregated into two major clades with lesser geographical separation. It also indicated common ancestry among the heme oxygenase proteins. This study highlights the potential conserved nature of heme oxygenase and can be treated as a target for therapeutics. However, further structural validation and experimental evidence is required to validate such potential. Keywords: Heme oxygenase, Leptospirosis, Leptospira interrogans, Multiple sequence alignment, Amino acid substitutions, Phylogenetic analysis
Choudhury et al. (Mon,) studied this question.