title: Lung surfactant dysfunction in tuberculosis: effect of mycobacterial tubercular lipids on dipalmitoylphosphatidylcholine surface activity.
abstract: In pulmonary tuberculosis, Mycobacterium tuberculosis bacteria reside in the alveoli and are in close proximity with the alveolar surfactant. Mycolic acid in its free form and as cord factor, constitute the major lipids of the mycobacterial cell wall. They can detach from the bacteria easily and are known to be moderately surface active. We hypothesize that these surface-active mycobacterial cell wall lipids could interact with the pulmonary surfactant and result in lung surfactant dysfunction. In this study, the major phospholipid of the lung surfactant, dipalmitoylphosphatidylcholine (DPPC) and binary mixtures of DPPC:phosphatidylglycerol (PG) in 9:1 and 7:3 ratios were modelled as lung surfactant monolayers and the inhibitory potential of mycolic acid and cord factor on the surface activity of DPPC and DPPC:PG mixtures was evaluated using Langmuir monolayers. The mycobacterial lipids caused common profile changes in all the isotherms: increase in minimum surface tension, compressibility and percentage area change required for change in surface tension from 30 to 10 mN/m. Higher minimum surface tension values were achieved in the presence of mycolic acid (18.2+/-0.7 mN/m) and cord factor (13.28+/-1.2 mN/m) as compared to 0 mN/m, achieved by pure DPPC film. Similarly higher values of compressibility (0.375+/-0.005 m/mN for mycolic acid:DPPC and 0.197+/-0.003 m/mN for cord factor:DPPC monolayers) were obtained in presence of mycolic acid and cord factor. Thus, mycolic acid and cord factor were said to be inhibitory towards lung surfactant phospholipids. Higher surface tension and compressibility values in presence of tubercular lipids are suggestive of an unstable and fluid surfactant film, which will fail to achieve low surface tensions and can contribute to alveolar collapse in patients suffering from pulmonary tuberculosis. In conclusion a biophysical inhibition of lung surfactant may play a role in the pathogenesis of tuberculosis and may serve as a target for the development of new drug loaded surfactants for this condition.
authors.affiliation: School of Biosciences & Bioengineering, Indian Institute of Technology, Mumbai 400076, India.
authors.forename: G
authors.initials: G
authors.lastname: Chimote
authors.forename: R
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000502:physiology*; D008055:Lipids / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D009171:Mycolic Acids / Q000737:chemistry* / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000502:physiology; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013500:Surface Tension; D014397:Tuberculosis, Pulmonary / Q000209:etiology* / Q000378:metabolism
chemical_list: D008055:Lipids; D009171:Mycolic Acids; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine