Exploring the Inhibitory Effects of Some Detergents on Mycobacterium avium subspecies paratuberculosis with Specific Focus on Zwitterionic Sulfobetaines
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) infects ruminants with Johne's disease and is also involved in human inflammatory bowel syndrome, such as Crohn's disease. With increasing drug resistance and zoonosis, there is a critical need for novel antimicrobial compounds having the potential to inhibit disease-causing bacteria. The present work examines the antimycobacterial activity of six detergent-like compounds, among which four are sulfobetaine-based zwitterionic detergents: amidosulfobetaine-14 (ASB-14), lauryl sulfobetaine (DDAPS), caprylyl sulfobetaine (D4266), and sulfobetaine 3-14 (SB3-14). Molecular docking and molecular dynamics (MD) simulations demonstrated higher binding affinities of ASB-14 and SB3-14 towards the carveol dehydrogenase (CD), catalase-related peroxidase (CRP), and dephospho-CoA kinase (DPCK) of MAP than the other compounds. MD simulation analysis showed less ligand root mean square deviation (RMSD) values for ASB-14 than SB3-14. MD simulations also revealed that certain regions in CRP and DPCK are perturbed to a greater extent upon binding to SB3-14 than ASB-14. Further, ADME studies and PASS predictions suggest good oral bioavailability and broad-spectrum bioactivity of both sulfobetaines, with minimal predicted toxicity for ASB-14, highlighting their efficacy as drug targets. Resazurin Microtiter Assay (REMA) indicates that SB3-14 exhibits inhibitory activity with a low MIC50 value of 0.0937 mg/mL, whereas ASB-14 inhibits MAP at 0.75…
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