title: Prospects of a new antistaphylococcal drug batumin revealed by molecular docking and analysis of the complete genome sequence of the batumin-producer Pseudomonas batumici UCM B-321.
abstract: Meticillin-resistant Staphylococcus aureus (MRSA) is a serious public health threat causing outbreaks of clinical infection around the world. Mupirocin is a promising anti-MRSA drug, however mupirocin-resistant strains of S. aureus are emerging at an increasing rate. The newly discovered antibiotic batumin may contribute to anti-MRSA therapy. The objective of this work was to identify possible molecular targets for batumin as well as mechanisms of its antistaphylococcal activity using computational molecular docking and by analysing the complete genome sequence of the batumin-producer Pseudomonas batumici UCM B-321. It was found that batumin acted very similarly to mupirocin by inhibiting aminoacyl tRNA synthetases. A previous hypothesis considering the trans-enoyl-CoA reductase FabI as a prime molecular target of batumin was rejected. However, indirect inhibition of fatty acid biosynthesis in sensitive bacteria does take place as a part of stringent response repression triggered by accumulation of uncharged tRNA molecules. Paralogues of diverse leucine-tRNA synthetases in the genome of P. batumici indicated that this protein might be the prime target of batumin. A batumin biosynthesis operon comprising 28 genes was found to be acquired through horizontal gene transfer. It was hypothesised that, in contrast to mupirocin, batumin could inhibit a broader range of aminoacyl tRNA synthetases and that acquired resistance to mupirocin might not endow S. aureus strains with resistance against batumin.
authors.affiliation: Department of Antibiotics, D.K. Zabolotny Institute of Microbiology and Virology, Kiev, Ukraine.
authors.forename: Vitalii V
authors.initials: VV
authors.lastname: Klochko
authors.affiliation: Department of Physiology of Industrial Microorganisms, D.K. Zabolotny Institute of Microbiology and Virology, Kiev, Ukraine.
authors.forename: Liubov B
authors.initials: LB
authors.lastname: Zelena
authors.affiliation: Centre for Bioinformatics and Computational Biology, Department of Biochemistry, University of Pretoria, Pretoria, South Africa.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Antibiotics, D.K. Zabolotny Institute of Microbiology and Virology, Kiev, Ukraine.
authors.forename: Lilia V
authors.initials: LV
authors.lastname: Avdeeva
authors.affiliation: Centre for Bioinformatics and Computational Biology, Department of Biochemistry, University of Pretoria, Pretoria, South Africa. Electronic address: oleg.reva@up.ac.za.
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Reva
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics; D016680:Genome, Bacterial; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D011549:Pseudomonas / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D009930:Organic Chemicals; C088306:batumin; D000604:Amino Acyl-tRNA Synthetases
keywords: Antistaphylococcal antibiotic; Batumin; Genome; Molecular docking; Mupirocin; Pseudomonas batumici