{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:51:13Z","timestamp":1790290273561,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Convocatoria de Proyectos de Investigaci\u00f3n SUE Distrito Capital","award":["60896"],"award-info":[{"award-number":["60896"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major cause of morbidity and mortality worldwide, particularly due to the emergence of drug-resistant strains. Membrane-active antimicrobial peptides (AMPs) represent attractive therapeutic candidates because they target bacterial envelope integrity and disrupt essential cellular processes. We evaluated two rationally designed LL-37-derived peptides: a truncated C-terminally amidated analog (LL37-1) and a modified variant incorporating N-terminal acetylation and a single D-amino acid substitution (D-LL37). Dose\u2013response analysis demonstrated that D-LL37 exhibited greater antimycobacterial potency, with lower inhibitory concentrations of 90% (IC90) and 50% (IC50) values (18.40 \u00b1 0.39 \u03bcM and 10.11 \u00b1 0.60 \u03bcM, respectively) compared with LL37-1 (25.44 \u00b1 0.36 \u03bcM and 15.45 \u00b1 1.40 \u03bcM). Fluorescence-based permeability assays revealed partial membrane disruption (36% and 44% at IC90 for LL37-1 and D-LL37, respectively), which was supported by ultrastructural alterations observed by scanning electron microscopy, including bacillary shortening, rough surface formation, cell clusters, and the presence of cellular debris, all of which are consistent with membrane damage. RT-qPCR analysis demonstrated significant upregulation of the P-type ATPase genes ctpF, ctpA, and ctpH following D-LL37 exposure. Collectively, these findings indicate that optimized LL-37-derived peptides exert antitubercular activity associated with envelope perturbation and coordinated activation of ion transport-related stress responses.<\/jats:p>","DOI":"10.3390\/biom16050665","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:35:53Z","timestamp":1777559753000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimized LL-37-Derived Peptides Exhibit Antitubercular Activity, Induce Membrane Disruption, and P-Type ATPase Transcriptional Responses in Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7356-083X","authenticated-orcid":false,"given":"Paola A.","family":"Santos","sequence":"first","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"},{"name":"Relaciones Microbianas y Epidemiol\u00f3gicas Aplicadas al Laboratorio Cl\u00ednico y Molecular\u2014REMA, Facultad de Ciencias de la Salud, Universidad Colegio Mayor de Cundinamarca, Calle 28 N\u00b0 5B-02, Bogot\u00e1 110311, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7752-4636","authenticated-orcid":false,"given":"Milena","family":"Maya-Hoyos","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz Mary","family":"Salazar","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Andrea","family":"Cruz","sequence":"additional","affiliation":[{"name":"Relaciones Microbianas y Epidemiol\u00f3gicas Aplicadas al Laboratorio Cl\u00ednico y Molecular\u2014REMA, Facultad de Ciencias de la Salud, Universidad Colegio Mayor de Cundinamarca, Calle 28 N\u00b0 5B-02, Bogot\u00e1 110311, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-863X","authenticated-orcid":false,"given":"Alver","family":"Cruz-Cacais","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9694-3958","authenticated-orcid":false,"given":"Mayerly","family":"Giraldo-Avila","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"G\u00f3mez-Manchego","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lineth Valentina","family":"Triana","sequence":"additional","affiliation":[{"name":"Relaciones Microbianas y Epidemiol\u00f3gicas Aplicadas al Laboratorio Cl\u00ednico y Molecular\u2014REMA, Facultad de Ciencias de la Salud, Universidad Colegio Mayor de Cundinamarca, Calle 28 N\u00b0 5B-02, Bogot\u00e1 110311, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8694-7489","authenticated-orcid":false,"given":"Carlos Y.","family":"Soto","sequence":"additional","affiliation":[{"name":"Bioqu\u00edmica y Biolog\u00eda Molecular de las Micobacterias\u2015BBMM, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 N\u00b0 45-03, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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