Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: A biophysical approach to disease

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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (217 K)Download as PowerPoint slideHighlights► A biophysical approach to TB was established by Langmuir isotherms, BAM and PM-IRRAS. ► High quantities of MAs enhanced the permeability of the PS model. ► The antimycobacterial compounds (RFB and RFB2) seem to be membrane ordering agents. ► In the MAs' presence, RFB and RFB2 improve the order of the PS model.