Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections.

The continuous rise of antimicrobial resistance urgently demands new therapeutic agents for human health. Drug repurposing is an attractive strategy that could significantly save time delivering new antibiotics to clinics. We screened 182 US Food and Drug Administration (FDA)-approved drugs to identify potential antibiotic candidates against Staphylococcus aureus, a major pathogenic bacterium. This screening revealed the significant antibacterial activity of three small molecule drugs against S. aureus: (1) LDK378 (Ceritinib), an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of lung cancer, (2) dronedarone HCl, an antiarrhythmic drug for the treatment of atrial fibrillation, and (3) eltrombopag, a thrombopoietin receptor agonist for the treatment of thrombocytopenia. Among these, eltrombopag showed the highest potency against not only a drug-sensitive S. aureus strain but also 55 clinical isolates including 35 methicillin-resistant S. aureus (Minimum inhibitory concentration, MIC, to inhibit 50% growth [MIC50] = 1.4-3.2 mg/L). Furthermore, we showed that eltrombopag inhibited bacterial growth in a cell infection model and reduced bacterial loads in infected mice, demonstrating its potential as a new antibiotic agent against S. aureus that can overcome current antibiotic resistance.

Leeia aquatica sp. nov., isolated from freshwater.

A Gram-stain-negative, rod-shaped, obligately aerobic, motile by a single polar flagellum, chemoheterotrophic bacterium, designated strain IMCC25680T, was isolated from surface water in Chungju Lake, Republic of Korea. 16S rRNA gene sequence analysis revealed that strain IMCC25680T was most closely related to Leeia oryzae HW7T with 95.5% sequence similarity and formed a robust clade with L. oryzae HW7T. Whole genome sequencing showed that strain IMCC25680T had a genome 3.6 Mbp long with 60.7 mol% DNA G+C content. Average nucleotide identity and digital DNA-DNA hybridization values between strain IMCC25680T and L. oryzae HW7T were 72.4% and 18.5%, respectively, indicating that the novel strain represents a novel species of the genus Leeia. The major cellular fatty acids of strain IMCC25680T were iso-C16:0 and summed feature 3 (comprising C16:1 ω6c and/or C16:1 ω7c). The respiratory quinone detected in the strain was ubiquinone-8. The major polar lipids were found to be phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified polar lipids. On the basis of the phylogenetic and phenotypic characterization, strain IMCC25680T was considered to represent a novel species within the genus Leeia, for which the name Leeia aquatica sp. nov. is proposed. The type strain is IMCC25680T (=KACC 19487T =NBRC 113132T).

Ferrimonas sediminicola sp. nov. and Ferrimonas aestuarii sp. nov., Fe(III)-reducing bacteria isolated from marine environments.

Two Gram-stain-negative, Fe(III)-reducing, facultatively anaerobic, motile via a single polar flagellum, rod-shaped bacterial strains, designated IMCC35001T and IMCC35002T, were isolated from tidal flat sediment and seawater, respectively. Results of 16S rRNA gene sequence analysis showed that IMCC35001T and IMCC35002T shared 96.6 % sequence similarity and were most closely related to Ferrimonas futtsuensis FUT3661T (98.6 %) and Ferrimonas kyonanensis Asr22-7T (96.8 %), respectively. Draft genome sequences of IMCC35001T and IMCC35002T revealed 4.0 and 4.8 Mbp of genome size with 61.0 and 51.8 mol% of DNA G+C content, respectively. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 73.1 and 19.8 %, respectively, indicating that they are separate species. The two genomes showed ≤84.4 % ANI and ≤27.8 % dDDH to other species of the genus Ferrimonas, suggesting that the two strains each represent novel species. The two strains contained both menaquinone (MK-7) and ubiquinones (Q-7 and Q-8). Major fatty acids of strain IMCC35001T were iso-C15 : 0, C18 : 1 ω9c, C17 : 1 ω8c and C16 : 0 and those of strain IMCC35002 T were C18 : 1 ω9c, C16 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Major polar lipids in both strains were phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipid, unidentified aminophospholipid and unidentified lipids. The two strains reduced Fe(III) citrate, Fe(III) oxyhydroxide, Mn(IV) oxide and sodium selenate but did not reduce sodium sulfate. They were also differentiated by several phenotypic characteristics. Based on the polyphasic taxonomic data, IMCC35001T and IMCC35002T were considered to represent each novel species in the genus Ferrimonas, for which the names Ferrimonas sediminicola sp. nov. (IMCC35001T=KACC 21161T=NBRC 113699T) and Ferrimonas aestuarii (IMCC35002T=KACC 21162T=NBRC 113700T) sp. nov. are proposed.