Inhibition of Filamentous Thermosensitive Mutant-Z Protein in Bacillus subtilis by Cyanobacterial Bioactive Compounds

Molecules

Svetlana Sushkova¹  Evgenya V. Prazdnova¹  Tatiana Minkina¹  Anuj Ranjan¹  Vishnu D. Rajput¹  Abhishek Chauhan²  Tanu Jindal²  Prangya Rath³  Manisha Gurnani³  Nada H. Aljarba⁴  Arabinda Ghosh⁵  Nobendu Mukerjee⁶  Saad Alkahtani⁷  Rup Lal⁸ 

[1] Academy of Biology and Biotechnology, Southern Federal University, 344006 Rostov-on-Don, Russia;Amity Institute of Environment Toxicology and Safety Management, Amity University, Noida 201303, India;Amity Institute of Environmental Sciences, Amity University, Noida 201301, India;Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia;Department of Botany, Microbiology Division, Guwahati University, Guwahati 781014, India;Department of Microbiology, Ramakrishna Mission Vivekananda Centenary College, Kolkata 700118, India;Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;Department of Zoology, University of Delhi, New Delhi 110007, India;

关键词: alpha-dimorphecolic acid;    docking;    Z-ring;    antibacterial drugs;    agar well diffusion assay;    molecular dynamics;   

DOI  :  10.3390/molecules27061907

来源: DOAJ

【 摘 要 】

Antibiotic resistance is one of the major growing concerns for public health. Conventional antibiotics act on a few predefined targets and, with time, several bacteria have developed resistance against a large number of antibiotics. The WHO has suggested that antibiotic resistance is at a crisis stage and identification of new antibiotics and targets could be the only approach to bridge the gap. Filamentous Temperature Sensitive-Mutant Z (Fts-Z) is one of the promising and less explored antibiotic targets. It is a highly conserved protein and plays a key role in bacterial cell division by introducing a cytokinetic Z-ring formation. In the present article, the potential of over 165 cyanobacterial compounds with reported antibiotic activity against the catalytic core domain in the Fts-Z protein of the Bacillus subtilis was studied. The identified cyanobacterial compounds were screened using the GLIDE module of Maestro v-2019-2 followed by 100-ns molecular dynamics (MD) simulation. Ranking of the potential compound was performed using dock score and MMGBSA based free energy. The study reported that the docking score of aphanorphine (−6.010 Kcalmol⁻¹) and alpha-dimorphecolic acid (ADMA) (−6.574 Kcalmol⁻¹) showed significant role with respect to the reported potential inhibitor PC190723 (−4.135 Kcalmol⁻¹). A 100 ns MD simulation infers that Fts-Z ADMA complex has a stable conformation throughout the progress of the simulation. Both the compounds, i.e., ADMA and Aphanorphine, were further considered for In-vitro validation by performing anti-bacterial studies against B. subtilis by agar well diffusion method. The results obtained through In-vitro studies confirm that ADMA, a small molecule of cyanobacterial origin, is a potential compound with an antibacterial activity that may act by inhibiting the novel target Fts-Z and could be a great drug candidate for antibiotic development.

【 授权许可】

Unknown