Author Correction: Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis

The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis

“…MDR-TB can be classified as resistance to first-line drugs isoniazid and rifampicin, and ultimately, extensive drug resistance (XDR) is resistance to first-line drugs and at least one second-line drug, i.e., amikacin, kanamycin, capreomycin or one of the fluoroquinolones [3,4]. Treatment for patients with MDR and XDR is often accompanied by prolonged and costly antibiotic courses and poor outcomes that result in high rates of mortality and treatment failure [5,6]. Countries that have a high burden of total cases of TB including DR-TB are often resource-limited.…”

“…DR-TB can be acquired during treatment through the acquisition of chromosomal mutations in drug target genes (secondary resistance) or can be transmitted from one individual to another (primary resistance) [6,8]. The development of acquired resistance is common as a result of single-nucleotide polymorphisms (SNPs), insertions and deletions [5,7]. Apart from chromosomal mutations, the intrinsic resistance due to the bacterium's lipid-rich Antibiotics 2021, 10, 857 2 of 14 cell wall and efflux pumps has limited the number of drugs that can treat TB [5,9].…”

“…The development of acquired resistance is common as a result of single-nucleotide polymorphisms (SNPs), insertions and deletions [5,7]. Apart from chromosomal mutations, the intrinsic resistance due to the bacterium's lipid-rich Antibiotics 2021, 10, 857 2 of 14 cell wall and efflux pumps has limited the number of drugs that can treat TB [5,9]. Rapid molecular diagnostic assays have been developed to tackle the challenge of early diagnosis and treatment.…”

“…For this reason, research has mostly focused on identifying multivariate associations between SNPs in the Mtb genome and the resistant phenotype. The application of mathematical methods in tandem with WGS and other related TB data has also proved to be vital in exploring the associations between TB variants [5,[14][15][16].…”

“…Newer work conducted by Zimic et al [24] identified 35 additional putatively novel compensatory mutations in rpoC genes from isolates that were rifampicin resistant in Peru. Another study conducted by Coll et al [5] identified a pnaB2 mutation that may compensate for pyrazinamide resistance conferred by pncA and mutations in the thyX-hsdS.1 promoter that compensates for para-aminosalicylic acid resistance conferred by mutations in thyA. The stated examples suggest that these strains may have undergone compensatory evolution modulating the fitness of the strains, which either precedes or follows the drug resistance acquisition by these strains [3,25,26].…”