title: The synthetic cathelicidin HHC-10 inhibits Mycobacterium bovis BCG in vitro and in C57BL/6 mice.
abstract: Tuberculosis causes close to 1.5 million deaths in the world, with new cases exceeding 9 million in recent years. Coinfection with HIV further worsens the global situation. New molecules that overcome the limitations of currently used drugs are needed. We aimed to determine whether HHC-10 is active against the Mycobacterium tuberculosis complex bacteria Mycobacterium bovis bacille calmette guerin (BCG) in vitro and in vivo. For this, HHC-10 was tested in vitro using different peptide concentrations, and in vivo, in C57BL/6 mice infected intratracheally, at two doses (1.25 and 2.5 mg kg(-1), once a week, 4 weeks). Interferon (IFN)-γ, TNF-α, interleukin (IL)-4, and IL-10 mRNA transcript levels were compared between treated and nontreated mice. In vitro, HHC-10 decreased 69% and 88% the number of colony-forming units (CFU) per millileter recovered after 24-hr treatment at 50 and 100 μg/ml, respectively. In vivo, BCG CFUs in mouse lungs were reduced 77.8% and 95.8% at 1.25 and 2.5 mg kg(-1), respectively. IFN-γ expression was lower in the HHC-10-treated group than that of nontreated animals. Considering genomic conservation between BCG and M. tuberculosis, the in vitro and in vivo activities of HHC-10 observed in this study suggest that the use of this peptide may be useful as therapeutic agent against tuberculosis.
authors.affiliation: Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, A.C., Guadalajara, Jalisco, México.
authors.forename: Yessica Yadira
authors.initials: YY
authors.lastname: Llamas-González
authors.forename: César
authors.initials: C
authors.lastname: Pedroza-Roldán
authors.forename: Marissa Beatriz
authors.initials: MB
authors.lastname: Cortés-Serna
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Márquez-Aguirre
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Gálvez-Gastélum
authors.forename: Mario Alberto
authors.initials: MA
authors.lastname: Flores-Valdez
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000254:growth & development; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents; C556062:IL10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D054804:Cathelicidins