Comparative genomics and phylogenetic analysis of Leptospira interrogans / Navamuganthan Murugan

Navamuganthan , Murugan (2019) Comparative genomics and phylogenetic analysis of Leptospira interrogans / Navamuganthan Murugan. Masters thesis, Universiti Malaya.

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Abstract

Leptospirosis is a re-emerging zoonotic disease worldwide and is caused by pathogenic strains of Leptospira spp. Most of the known serovars are isolated from their prime reservoirs of domestic and wild animals. Humans are infected either directly or in directly with exposure to the contaminated soil, water or urine of infected animals. However, very little is known about the genetics and virulence of Leptospira interogans that enable it to persist in environment and the reservoirs. Next Generation sequencing and advances in computational analysis have facilitated our understanding on the genomics of the causative agent of Leptospires. Three Malaysian strains of L. interrogans of different serovars isolated from three different hosts that is dog (D7), humans (L52) and rat (R123) were sequenced using the Illumina HiSeq 2000 platform. A5-miseq pipeline was used to perform de novo assembly. Genomes of 86 reference strains were obtained from National Center for Biotechnology Information (NCBI) database representing global sources. The protein coding sequences of the 89 genomes was determined independently using automated PROKKA annotation programs. Functional annotation of coding sequences of three Malaysian L. interrogans genomes were further determined using eggNOG-mapper. Conservation of the genes among 89 genomes was further examined using Roary program followed by pan-genome and evolutionary analysis using BPGA computational analysis. The draft genome sizes of D7, L52 and R123 are 4.70 Mbp, 4.88 Mbp and 4.80 Mbp, respectively. Comparative genomic analysis between Malaysian and global reference strains of L. interrogans have identified conserved functional genes involved in morphology determination (mrdB, mreB and mreC), adaptation (cat, lexA and recA), resistance (katA, ccp, ccpA and tpx), adhesion (tlyC, ligA, inlA, slrP, sspH1 and sspH2), invasion (colA and npr), gene regulation (degU, hupR1, pdtaR, and zraR), metabolism (cbi, cob, sir, psel, legF, neuA and neuB), chemotaxis (cheA, cheB, cheC, cheD, cheR, cheW, cheX, cheY, mcp2, mcp3, mcp4, mcpA, mcpB, pctB, pctC, pomA, tar and tsr), motility (cheD, cheR, cheW, flaAL, flaB, flgB, flgE, flgK, flgC flgG, fliD, fliE fliG, fliM, fliN, mcp4, motB, pomA and ycgR) and virulence factors (hlb, tlyAC, smcL, sph, cirA, htrB, kdsA, kdsB, kdsD, lpxA, lpxB, lpxC, lpxD, lpxK, waaA, cssS, liaS, mprA, pleD, rcp1, rcsC, tmoS, todS and uvrY). The pan genome is considered still open but maybe closed soon. L. interrogans is endowed with many genes that enable it to colonise different hosts. Phylogenetic study showed that strains of the same serovar isolated from different hosts and geographic locations are clustered together. The three Malaysian strains of L. interrogans D7, L52 and R123 appeared to be ancestrally related to the South America and Asia sub-clusters.

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