Isolation and comparative genomics of Mycobacterium tuberculosis isolates from cattle and their attendants in South India

Kannan Palaniyandi,Soumya Swaminathan,Sharon J Peacock,Ananthi Rajendran,Subramanyam Balaji,Dhinakar Raj,Kannan Thiruvengadam,Sujatha Narayanan,Ahmed Kabir Refaya,Maroudam Veerasamy,Narender Kumar,Chandrakumar Dolla,Dhanaraj Baskaran

doi:10.1038/s41598-019-54268-x

Abstract

The major human pathogen Mycobacterium tuberculosis is rarely reported to cause disease in other animals. Cases in livestock are thought to occur through contact with infected handlers, but previous studies evaluating putative livestock-human transmission used typing techniques with limited resolution. Here, we undertook cross-sectional surveillance for tuberculosis in 271 livestock handlers and 167 cattle on three farms in Chennai, India and defined the relatedness of cultured isolates using whole genome sequencing. Humans and livestock were screened for active mycobacterial infection, and opportunistic post-mortem examination was performed on comparative intradermal test-positive cattle that died. Four cattle and 6 handlers on two farms were culture-positive for M. tuberculosis; M. bovis was not isolated. All 10 isolates (one from each case) belonged to Lineage 1. Pairwise genome comparisons of single nucleotide polymorphism (SNP) differences ranged from 1 to 600 SNPs, but 3 isolate pairs were less than 5 SNPs different. Two pairs were from handlers and the third pair were from two cattle on the same farm. The minimum pairwise SNP difference between a cattle and human isolate was >250 SNPs. Our study confirms the presence of M. tuberculosis infection in cattle in India, sequencing of which characterised relatedness between human and cattle-derived isolates.

Highlights

Mycobacterium tuberculosis and Mycobacterium bovis are the predominant cause of tuberculosis in humans and cattle, respectively[1]
We describe an observational study of M. tuberculosis infection in cattle and their handlers at 3 farms in Chennai, India, in which we integrated the findings of an epidemiological investigation with bacterial culture, identification and whole genome sequencing
Several independent studies from the late 19th century onwards reported that M. tuberculosis was avirulent in cattle[13,14,15], but recent reports of M. tuberculosis infection in livestock[2,5,6] have led this to be experimentally re-evaluated

Summary

Introduction

Mycobacterium tuberculosis and Mycobacterium bovis are the predominant cause of tuberculosis in humans and cattle, respectively[1]. In a study using IS6110-based restriction fragment length polymorphism (RFLP) typing, M. tuberculosis isolated from cattle and a handler had an identical pattern, suggesting transmission between them[7]. We describe an observational study of M. tuberculosis infection in cattle and their handlers at 3 farms in Chennai, India, in which we integrated the findings of an epidemiological investigation with bacterial culture, identification and whole genome sequencing.

Results

Conclusion