Comparative genomic analysis of paired clinical isolates from a patient with recurrent melioidosis reveals a low within-host mutation rate.

Abstract

Introduction. Relapse of melioidosis is not uncommon and can occur due to shorter oral antibiotic therapy in the first episode. In such isolates, low mutation rates were identified amongst paired clinical isolates during relapse, but large-scale structural variants were also common.Hypothesis. Using pair-wise comparison, a low number of mutations, especially amongst the virulence and antibiotic resistance genes, may be present amongst the paired isolates obtained during the study period.Aim. A pair of clinical isolates obtained from a patient with recurrent melioidosis during the study period (January 2018 to June 2021) was analysed for identifying the genomic relatedness and DNA changes that may have caused the relapse.Methodology. Using paired-end Illumina sequencing, following appropriate data quality checks, the genomes were assembled using Shovill pipeline, whilst the variants were called using Snippy. Structural variants were detected using TIDDIT, and functional associations were identified using the STRING database searches.Results. One of the isolates (from the second episode) had a highly fragmented genome, but very few structural variants and SNPs were identified. Both the isolates had similar virulence and antibiotic resistance genes; however, owing to the few structural changes, a slightly lower number of virulence genes were observed. Together, they shared 99.8% of the proteomes, and most variants identified spanned either hypothetical proteins or un-annotated regions.Conclusions. Based on comprehensive genome analysis the two strains were genetically similar, with a few structural variants, implying the second episode to be a relapse rather than a re-infection. There was no difference in the antibiotic resistance or virulence genes that may have explained the relapse.