Table 2.
Summary of known biomarkers for drug resistance in L. infantum. Summary of locus, gene ID, function, and reported gene copy number variation of the nine genomic regions (22 loci) analyzed related to pathogenicity or drug resistance in L. infantum. Gene ID, Start, and End correspond to the L. infantum reference genome (L. infantum JPCM5 v2/2018) [18]. CNV: Expansion or deletion of gene copy number. R: Resistant; TF: Treatment failure. A reference is provided for studies showing threshold resistance effect by CNVs.
| Biomarker | Gene ID | Start | End | Gene Name | Function | Gene CNVs | Resistance/Pathogenicity | Reference |
|---|---|---|---|---|---|---|---|---|
| Miltefosine sensitivity locus (MSL) | LinJ.31.2370 | 1,181,281 | 1,182,328 | LinJ.31.2370 | 3′-nuclease | Deletion (CN −2) | Miltefosine TF | [27] |
| LinJ.31.2380 | 1,184,204 | 1,185,341 | LinJ.31.2380 | 3′-nuclease | ||||
| LinJ.31.2390 | 1,185,826 | 1,188,553 | LinJ.31.2390 | Helicase-like protein | ||||
| LinJ.31.2400 | 1,191,356 | 1,192,406 | LinJ.31.2400 | 3-2-trans-enoyl-CoA isomerase | ||||
| Miltefosine transporter and associated genes | LinJ.13.1590 | 570,912 | 574,206 | LdMT | Phospholipid transport | Deletion (CN −1, −2) | Miltefosine R | [28] |
| LinJ.13.1600 | 576,108 | 577,572 | Hypot. protein | Unknown | ||||
| LinJ.32.1040 | 392,366 | 393,596 | ldRos3 | Vps23 core domain | ||||
| LACK antigen | LinJ.28.2940 | 1,070,377 | 1,071,316 | LACK1 | Antigenic protein | Expansion | Pathogenicity | [29] |
| LinJ.28.2970 | 1,074,409 | 1,075,348 | LACK2 | |||||
| Paromomycin-resistant locus | LinJ.27.1940 | 942,538 | 944,020 | D-LDH | D-lactate dehydrogenase | Expansion (CN +1) | Paromomycin (PMM) R | [30] |
| LinJ.27.1950 | 946,545 | 947,751 | B-CAT | Branched-chain amino acid aminotransferase | ||||
| MAPK1 | LinJ.36.6760 | 2,564,560 | 2,565,637 | LMPK | Mitogen-activated protein kinase | Conflicting evidence | Trivalent antimonials R | [31] |
| AQP1 | LinJ.31.0030 | 8,742 | 9,687 | AQP1 | Aquaglyceroporin 1 | Deletion (CN −1) | Trivalent antimonials R | [31] |
| H locus | LinJ.23.0280 | 86,372 | 86,942 | YIP1 | Unknown | Expansion (CN +1) MRPA and PTR1 | Trivalent antimonials R | [28] |
| LinJ.23.0290 | 88,619 | 93,329 | MRPA | ABC-thiol transporter | ||||
| LinJ.23.0300 | 94,265 | 95,522 | LinJ.23.0300 | Arginosuccinate synthase | ||||
| LinJ.23.0310 | 101,314 | 102,181 | PTR1 | Pteridine reductase 1 | ||||
| METK locus | LinJ.30.3550 | 1,283,752 | 1,284,865 | Lorien protein | Deletion (CN −1) | Allopurinol R | [10] | |
| LinJ.30.3560 | 1,285,559 | 1,286,738 | METK1 | S-adenosylmethionine synthetase | ||||
| LinJ.30.3570 | 1,288,872 | 1,289,985 | Lorien protein | |||||
| LinJ.30.3580 | 1,290,679 | 1,291,858 | METK2 | S-adenosylmethionine synthetase |