title: Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.
abstract: This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Giner-Casares
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: João M
authors.initials: JM
authors.lastname: Caio
authors.forename: Cristina
authors.initials: C
authors.lastname: Moiteiro
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: Luis
authors.initials: L
authors.lastname: Camacho
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008956:Models, Chemical; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D009171:Mycolic Acids / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry; D010743:Phospholipids / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D011663:Pulmonary Surfactants / Q000737:chemistry*; D017828:Rifabutin / Q000494:pharmacology; D013053:Spectrophotometry / Q000379:methods; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001688:Biological Products; D008055:Lipids; D009171:Mycolic Acids; D010718:Phosphatidylserines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D017828:Rifabutin; D015060:1,2-Dipalmitoylphosphatidylcholine; C068291:poractant alfa