The Evolution of Strain Typing in the Mycobacterium tuberculosis Complex

Abstract

Tuberculosis (TB) is a contagious disease with a complex epidemiology. Therefore, molecular typing (genotyping) of Mycobacterium tuberculosis complex (MTBC) strains is of primary importance to effectively guide outbreak investigations, define transmission dynamics and assist global epidemiological surveillance of the disease. Large-scale genotyping is also needed to get better insights into the biological diversity and the evolution of the pathogen. Thanks to its shorter turnaround and simple numerical nomenclature system, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) typing, based on 24 standardized plus 4 hypervariable loci, optionally combined with spoligotyping, has replaced IS6110 DNA fingerprinting over the last decade as a gold standard among classical strain typing methods for many applications. With the continuous progress and decreasing costs of next-generation sequencing (NGS) technologies, typing based on whole genome sequencing (WGS) is now increasingly performed for near complete exploitation of the available genetic information. However, some important challenges remain such as the lack of standardization of WGS analysis pipelines, the need of databases for sharing WGS data at a global level, and a better understanding of the relevant genomic distances for defining clusters of recent TB transmission in different epidemiological contexts. This chapter provides an overview of the evolution of genotyping methods over the last three decades, which culminated with the development of WGS-based methods. It addresses the relative advantages and limitations of these techniques, indicates current challenges and potential directions for facilitating standardization of WGS-based typing, and provides suggestions on what method to use depending on the specific research question.

Corynebacterium silvaticum sp. nov., a unique group of NTTB corynebacteria in wild boar and roe deer

“…Multi locus sequence typing (MLST) is one of the most common tools for molecular typing [5,6], widely used for C. diphtheriae [7] and C. ulcerans [8] and implemented for delineating species within bacterial genera [9]. Currently, whole genome sequencing (WGS) offers the highest molecular resolution and is increasingly used for typing and phylogenetic classification of various pathogens, including corynebacteria [10][11][12][13].…”

Communicable Disease Surveillance Ethics in the Age of Big Data and New Technology

“…Over the past 20 years, increasingly sophisticated genotypic methods have been developed for pathogen strain typing but, until recently, most have been expensive, timeconsuming and/or not particularly discriminatory and mainly used for retrospective outbreak investigation. However, newer strain typing methods have been used routinely, for several years, to improve detection of outbreaks due to, for example, Mycobacterium tuberculosis (Merker et al 2017), foodborne pathogens, such as Salmonella Enteritidis and its numerous serovars (Campioni et al 2015), and nosocomial pathogens such as methicillin-resistant Staphylococcus aureus (O'Sullivan 2006). Pathogen whole-genome sequencing (WGS) is the ultimate strain typing method.…”

PathOGiST: A Novel Method for Clustering Pathogen Isolates by Combining Multiple Genotyping Signals

“…Genotpying methods have several applications such as clustering bacterial samples into strains [28], and reconstructing a chain of transmission events [27]. These tasks are not trivial as bacteria evolve quickly and in a variety of ways.…”