Identification of a predominant genotype of Mycobacterium tuberculosis in Brazilian indigenous population

Abstract

After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.

Genetic Diversity of Mycobacterium tuberculosis Isolates From an Amerindian Population in Chiapas, México

“…The Latino-American family (Lineage 4.3) has been observed to predominate in South America ( Brynildsrud et al., 2018 ). Interestingly in a recent study using samples from the Guarani-Kaiowaí indigenous people living in Paraguay and the Brazilian state of Mato Grosso do Sul, Hadi et al. (2021) found that 81% of the isolates belong to sub-lineage 4.3.3, followed by 4.3.4.2 (13%), in a similar way to our findings ( Hadi et al., 2021 ).…”

“…In both cases, Amerindian people were the hosts, which makes possible the adaptation of these sub-lineages to people with this genetic background, as has been seen in Tanzania where L3.1.1 is highly successful in Dar es Salam ( Zweyer et al., 2021 ). The comparison of our 4.3.3 genomes with those from Hadi et al.’s (2021) study resulted in the formation of a separated cluster with two Amazonian isolates in the group, which strengthen the possible relationship with South American isolates. These Chiapas’ 4.3.3 isolates, even if they were not identical, showed a similar pattern in mutations in genes associated with antimicrobial resistance.…”

“…When comparing the genomes of SIT42 or orphan isolates belonging to lineage 4.3.3 with the genomes of MTB isolates from Amazonic Amerindian populations of Brazil ( Hadi et al., 2021 ), the Mexican genomes, except for CH2, clustered together, with two Amazonic isolates (SAMN16448874 and SAMN16448910) intercalated among them ( Figure 6 ).…”

“…The three earliest migration events to America were inferred to have occurred between 1466 and 1593 to South America and between 1566 and 1658 to North America ( Brynildsrud et al., 2018 ). Most of our SIT 53 isolates belonged to lineage 4.8, which is not commonly found in America, where 4.3.3 dominates ( Hadi et al., 2021 ). This might be explained by groups of people from Spain, where Lineage 4 is predominant ( Madrazo Moya et al., 2021 ), or Portugal who migrated to Mexico or South America carrying different sub-lineages, or to the adaptation through the years to the local hosts, as has been observed in in vivo experiments ( Reiling et al., 2013 ).…”

“…These Chiapas isolates belong to the group sharing mutations at the gyrA gene at nucleotides 7362, 7585, 8040, and 9304. CH2 (SIT42) and CH24 (ORF) were other 4.3.3 isolates that shared the gyrA mutations but clustered close to isolates of When comparing the genomes of SIT42 or orphan isolates belonging to lineage 4.3.3 with the genomes of MTB isolates from Amazonic Amerindian populations of Brazil (Hadi et al, 2021), the Mexican genomes, except for CH2, clustered together, with two Amazonic isolates (SAMN16448874 and SAMN16448910) intercalated among them (Figure 6).…”