Paradoxical Bactericidal Effects of Hydrophobic Lung Surfactant Proteins and Their Peptide Mimics Using Liposome Molecular Trojan

Abstract

Lung surfactant, besides alveolar stability, also provides defence against pathogens by surfactant proteins (SP), SP-A and SP-D. The hydrophobic proteins SP-B and SP-C enhance surface activity. An unusual and paradoxical effect of bovine LS and synthetic model LS with SP-B/-C was bactericidal to Staphylococcus aureus and Escherichia coli. Bacterial proliferation were investigated with bovine lung surfactant extract (BLES), dipalmitoylphosphatdylcholine, palmitooleylglycerol, in combination with SP-B/-C using standard microbiological colony forming unit (CFU) counts and structural imaging. BLES and other surfactant-SP-B/-C mixtures inhibit bacterial growth in the concentration range of 0 -7.5 mg/mL, at > 10 mg/mL paradoxical growth of both the bacterial species suggest antibiotic resistance. The lipid only LS have no effect on bacterial proliferation. Smaller peptide mimics of SP-B or SP-B, were less efficient than SP-C. Ultra structural studies of the bacterial CFU using electron and atomic force microscopy suggest some membrane damage of S. aereus at inhibitory concentration of BLES, and some structural alteration of E. coli at dividing zones, suggesting utilization and incorporation of surfactant lipid species by both bacteria. The results depicted from in vitro studies are also in agreement with protein-protein interactions obtained from PatchDock, FireDock and ClasPro algorithm. The MD-simulation decipher a small range fluctuation of gyration radius of the LS proteins and their peptide mimics. The studies have alarming implications in the use of high dosages (100 mg/mL/kg body weight) of exogenous surfactant for treatment of respiratory distress syndrome, genetic knock-out abnormalities associated with these proteins, and the novel roles played by SP-B/C as bactericidal agents.

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

“…The amino acid sequence of the viral RdRp was scanned for identification of known functional domains/motifs using InterPro Scanner (Hunter, Apweiler et al 2009). Homology modeling of the RdRp was carried out using SwissModel and quality was checked using PROCHECK (Dutta, Nag et al 2018). Rigid-body molecular docking between several established antiviral drugs and RdRp from SARS-CoV-2 was carried out using AutoDock (v4.2), (Dutta, Shityakov et al 2018).…”

Physical properties of phospholipids and integral proteins and their biofunctional roles in pulmonary surfactant from molecular dynamics simulation

“…This model is adopted in several recent reports. 13,[27][28][29] In the MARTINI model, each amino acid is represented by a single bead that can be polar (sL), non-polar (sH) or neutral (tN). The sL and sH beads are mutually repulsive and differ only in the parameterization of their respective dihedral potentials.…”

“…Their simulation results revealed that, when brought into contact with pulmonary surfactant, silver and polystyrene nanoparticles are immediately covered with a biomolecular corona composed of both lipids and proteins. In another recently published paper, K. Dutta et al 29 studied the paradoxical bactericidal effects of hydrophobic lung surfactant proteins and their peptide mimics using a molecular Trojan horse liposome. This study has alarming implications in using high dosage exogenous surfactant for treatment of respiratory distress syndrome, genetic knock-out abnormalities associated with these proteins, and the novel roles played by SP-B/C as bactericidal agents.…”

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

“…Homology modeling of the RdRp was carried out using SwissModel and quality was checked using PROCHECK [16]. Rigid-body molecular docking between several established antiviral drugs and RdRpSARS-CoV-2 was carried out using AutoDock (v4.2), [14].…”