Estimation of the global burden of Mycobacterium tuberculosis lineage 1

Netikul, Thidarat; Palittapongarnpim, Prasit; Thawornwattana, Yuttapong; Plitphonganphim, Supada

doi:10.1016/j.meegid.2021.104802

Cited by 30 publications

(36 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mycobacterium tuberculosis (Mtb) is classified into 9 lineages 1 – 3 , with lineages 1–4 (L1–L4) being widely distributed around the world. Mtb L1, or the India-Oceanic lineage, is the only TbD1-positive Mtb lineage with high incidences in many high-burden countries around the Indian Ocean 4 . Although whole genome sequencing (WGS) is increasingly used for studying Mtb, our understanding of L1 genetic diversity and epidemiology in high-burden settings remains limited.…”

Section: Introductionmentioning

confidence: 99%

Whole-genome single nucleotide variant phylogenetic analysis of Mycobacterium tuberculosis Lineage 1 in endemic regions of Asia and Africa

Netikul

Thawornwattana

Mahasirimongkol

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) lineage 1 (L1) contributes considerably to the disease morbidity. While whole genome sequencing (WGS) is increasingly used for studying Mtb, our understanding of genetic diversity of L1 remains limited. Using phylogenetic analysis of WGS data from endemic range in Asia and Africa, we provide an improved genotyping scheme for L1. Mapping deletion patterns of the 68 direct variable repeats (DVRs) in the CRISPR region of the genome onto the phylogeny provided supporting evidence that the CRISPR region evolves primarily by deletion, and hinted at a possible Southeast Asian origin of L1. Both phylogeny and DVR patterns clarified some relationships between different spoligotypes, and highlighted the limited resolution of spoligotyping. We identified a diverse repertoire of drug resistance mutations. Altogether, this study demonstrates the usefulness of WGS data for understanding the genetic diversity of L1, with implications for public health surveillance and TB control. It also highlights the need for more WGS studies in high-burden but underexplored regions.

show abstract

Section: Introductionmentioning

confidence: 99%

Whole-genome single nucleotide variant phylogenetic analysis of Mycobacterium tuberculosis Lineage 1 in endemic regions of Asia and Africa

Netikul

Thawornwattana

Mahasirimongkol

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although, pre-symptomatic transmission could be more important than previously thought (Kendall et al 2021). There is some indirect evidence for a longer asymptomatic period in L1: a recent study estimated that asymptomatic infection is longer in TB patients in Southeast Asian countries such as Lao, Cambodia, and the Philippines (Ku et al 2021), where L1 is responsible for more than half of TB cases (Schopfer et al 2015, Chen et al 2017, Somphavong 2018, Netikul et al 2021). In these countries latency was found to be up to three times longer compared to Pakistan, Ethiopia and Zambia, where L1 is rare (Mulenga et al 2010, Firdessa et al 2013, Chihoota et al 2018, Tulu & Ameni 2018, Wiens et al 2018, Ali et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis

Menardo

2022

Preprint

View full text Add to dashboard Cite

Detecting factors associated with transmission is important to understand disease epidemics, and to design effective public health measures. Clustering and terminal branch lengths (TBL) analyses are commonly applied to genomic data sets of Mycobacterium tuberculosis (MTB) to identify sub-populations with increased transmission. Here, I used a simulation-based approach to investigate what epidemiological processes influence the results of clustering and TBL analyses, and whether difference in transmission can be detected with these methods. I simulated MTB epidemics with different dynamics (latency, infectious period, transmission rate, basic reproductive number R0, sampling proportion, and molecular clock), and found that all these factors, except the length of the infectious period and R0, affect the results of clustering and TBL distributions. I show that standard interpretations of this type of analyses ignore two main caveats: 1) clustering results and TBL depend on many factors that have nothing to do with transmission, 2) clustering results and TBL do not tell anything about whether the epidemic is stable, growing, or shrinking. An important consequence is that the optimal SNP threshold for clustering depends on the epidemiological conditions, and that sub-populations with different epidemiological characteristics should not be analyzed with the same threshold. Finally, these results suggest that different clustering rates and TBL distributions, that are found consistently between different MTB lineages, are probably due to intrinsic bacterial factors, and do not indicate necessarily differences in transmission or evolutionary success.

show abstract

“…We next sought to explore the possibility that the common Gly64delG mutation may render this subset of Mtb strains hypersusceptible to and treatable with macrolides. Lineage calling identified the Gly64delG SNP as uniquely present in all lineage 1.2.1 (L1.2.1) Mtb isolates, a major sublineage of the L1 Indo-Oceanic clade (Figure 6A; Supplemental Figure 9B; Supplemental Data 8) (Netikul et al, 2021). Using a reference set of Mtb clinical strains (Borrell et al, 2019), we first validated the presence of the whiB7 Gly64delG frameshift mutation in L1.2.1 by Sanger sequencing (Figure 6B).…”

Section: Tuberculosis Hypersusceptible To Macrolidesmentioning

confidence: 99%

“…Of note, the Philippines has one of the highest TB incidence rates in the world, including a high burden of drug-resistant TB, and TB is a leading cause of death in this country (WHO, 2021). A recent analysis of the global burden of TB caused by L1.2.1 estimates that this sublineage causes approximately 600,000 cases of active TB per year (Netikul et al, 2021), of which ~43,000 are estimated to be MDR-TB based on the frequencies of drug resistance in our clinical strain genome database. Thus, clarithromycin, an effective, orally available, safe, and generic antibiotic, could potentially be repurposed to treat a major sublineage of TB.…”

Section: Tuberculosis Hypersusceptible To Macrolidesmentioning

confidence: 99%

A chemical-genetic map of the pathways controlling drug potency in Mycobacterium tuberculosis

Poulton

Chang

et al. 2021

Preprint

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) infection is notoriously difficult to treat. Treatment efficacy is limited by Mtb’s intrinsic drug resistance, as well as its ability to evolve acquired resistance to all antituberculars in clinical use. A deeper understanding of the bacterial pathways that govern drug efficacy could facilitate the development of more effective therapies to overcome resistance, identify new mechanisms of acquired resistance, and reveal overlooked therapeutic opportunities. To define these pathways, we developed a CRISPR interference chemical-genetics platform to titrate the expression of Mtb genes and quantify bacterial fitness in the presence of different drugs. Mining this dataset, we discovered diverse and novel mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining chemical-genetics with comparative genomics of Mtb clinical isolates, we further identified numerous new potential mechanisms of acquired drug resistance, one of which is associated with the emergence of a multidrug-resistant tuberculosis (TB) outbreak in South America. Lastly, we make the unexpected discovery of an “acquired drug sensitivity.” We found that the intrinsic resistance factor whiB7 was inactivated in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to potentially repurpose the macrolide antibiotic clarithromycin to treat TB. This chemical-genetic map provides a rich resource to understand drug efficacy in Mtb and guide future TB drug development and treatment.

show abstract

Estimation of the global burden of Mycobacterium tuberculosis lineage 1

Cited by 30 publications

References 27 publications

Whole-genome single nucleotide variant phylogenetic analysis of Mycobacterium tuberculosis Lineage 1 in endemic regions of Asia and Africa

Whole-genome single nucleotide variant phylogenetic analysis of Mycobacterium tuberculosis Lineage 1 in endemic regions of Asia and Africa

Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis

A chemical-genetic map of the pathways controlling drug potency in Mycobacterium tuberculosis

Contact Info

Product

Resources

About