{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:16:44Z","timestamp":1783621004687,"version":"3.55.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PROCIENCIA","award":["106-2021-FONDECYT"],"award-info":[{"award-number":["106-2021-FONDECYT"]}]},{"name":"Universidad Peruana de Ciencias Aplicadas","award":["A-054-2021-2"],"award-info":[{"award-number":["A-054-2021-2"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Tuberculosis (TB) remains a critical public health crisis in Peru, which bears the highest multidrug-resistant TB (MDR-TB) burden in the Americas. The objective of this study was to conduct a nationwide genetic surveillance of first- and second-line drug-resistant\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    isolates in Peru to characterize their structural and geographic distribution using a multilocus genotype approach. We analyzed 38,339 valid results from first- and second-line line probe assays (LPA 1L, GenoType MTBDR\n                    <jats:italic>plus<\/jats:italic>\n                    v2; and LPA 2L, GenoType MTBDR\n                    <jats:italic>sl<\/jats:italic>\n                    v2) routinely collected between 2019 and 2022 by the Peruvian National Institute of Health. First-line (G1) and second-line (G2) multilocus genotypes were generated by concatenating specific hybridization banding patterns across resistance-associated loci. Additionally, targeted next-generation sequencing was performed on a stratified proportional sample of 170 isolates exhibiting \u201cinferred\u201d resistance genotypes, defined by a missing wild-type signal without a corresponding mutant probe, to elucidate their underlying mutational profiles. Resistance genotypes were identified in 13.5% and 11.8% of LPA 1L and LPA 2L results, respectively. The genotypic landscape was highly concentrated: 13 dominant G1 genotypes and 19 dominant G2 genotypes accounted for over 85% of their respective resistant cohorts. Structurally, these dominant genotypes mainly carried globally successful, canonical mutations (e.g.,\n                    <jats:italic>katG<\/jats:italic>\n                    S315T1,\n                    <jats:italic>rpoB<\/jats:italic>\n                    S450L). Geographically, dominant genotypes were heavily consolidated within the hyper-endemic central coastal axis (Lima, Callao, and Ica) and the Amazonian department of Ucayali, maintaining highly stable temporal frequencies. Conversely, heteroresistance and complex multi-mutational patterns were exclusively restricted to low-frequency rare and orphan genotypes. Targeted sequencing of inferred patterns successfully expanded the national catalog of resistance variants, identifying non-canonical determinants (e.g.,\n                    <jats:italic>inhA<\/jats:italic>\n                    g-17t,\n                    <jats:italic>gyrB<\/jats:italic>\n                    T500N) and preventing false-positive resistance calls driven by synonymous mutations. This large-scale mapping demonstrates that Peru\u2019s drug-resistant TB epidemic is characterized by the widespread consolidation of a restricted number of canonical multilocus genotypes. Integrating targeted sequencing with routine molecular screening is essential to resolve unclassified hybridization patterns and optimize epidemiological management in high-burden settings.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352881","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:31:56Z","timestamp":1783618316000},"page":"e0352881","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic surveillance of first- and second-line drug-resistant isolates of Mycobacterium tuberculosis in Peru"],"prefix":"10.1371","volume":"21","author":[{"given":"David","family":"Santos-L\u00e1zaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko N.","family":"Vigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidia V.","family":"Cotrina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Villar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Julcapoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam J.","family":"Alarc\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-0986","authenticated-orcid":true,"given":"Zully M.","family":"Puy\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"pone.0352881.ref001","unstructured":"World Health Organization. Global Tuberculosis Report 2025. 2025. https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2025"},{"key":"pone.0352881.ref002","unstructured":"World Health Organization. Global tuberculosis report 2024. World Health Organization. 2024. https:\/\/iris.who.int\/bitstream\/handle\/10665\/379339\/9789240101531-eng.pdf?sequence=1"},{"key":"pone.0352881.ref003","unstructured":"WHO announces updated definitions of extensively drug-resistant tuberculosis. https:\/\/www.who.int\/news\/item\/27-01-2021-who-announces-updated-definitions-of-extensively-drug-resistant-tuberculosis 2023 December 4."},{"key":"pone.0352881.ref004","unstructured":"Geneva: World Health Organization. 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