Antimicriobial Activity Of Novel Polymyxin Against Multi-drug-resistant Bacteria And Taxonomy And Mechanisms Of Antimicriobial Resistance In Marine Bacteria NH1~T

The extensive use of antibiotics has led to the emergence of a growing number of resistant bacteria, which threatens the effective prevention and treatment of bacterial infections. It is an increasingly serious threat to the public health and there is an urgent need to understand the bacterial resistance mechanisms and to develop novel antibiotics to treat drug-resistant bacteria. Polymyxin is a multicomponent, cationic polypeptide and Polymyxin B and colistin are active against Gram-negative pathogens only and have been used in the clinic as the last-line therapy. A novel polymyxin FADDI-019 exhibited activity against Gram-positives. In this study, we analysed the antimicrobial activity of FADDI-019 against vancomycin-resistant Staphylococcus aureus (VRSA). The antibiotic sensitivity tests show that although Vancomycin-resistant Staphylococcus aureus is resistant to polymyxin B, E, both strains were sensitive to FADDI-019 and no regrowth was observed after 24 h. The absence of morphological changes in scanning electron microscopy indicated that action of FADDI-019 against VRSA was not a direct effect of the membrane damage. The transcriptomic data show that after treated with FADDI-019, a total of 208 differentially regulated genes were identified. Of the 208 differentially regulated genes,140 were significantly up-regulated which include vancomycin resistance regulon, genes involved in the metabolism of amino acids, energy, folate and 68 significantly down-regulated, including key virulence factors which indicates that in addition to killing VRSA ATCC 700699, FADDI-019 can also reduce infection virulence. Our pathway analysis indicated that amino acid metabolism is dependent on folate metabolism and that the tetrahydrofolate synthesis pathway is a suitable chokepoint to inhibit both processes; we finally tested the MICs of combination therapies of sulfamethoxazole with FADDI-019 against VRSA. These results demonstrated synergy between sulfamethoxazole and FADDI-019. Synergistic therapies provide viable alternative means of treating infections using combinations of existing therapies that show greater antimicrobial activity together than individually.We also analysed the antibiotics susceptibility and drug-resistance genes of NH1T, which was isolated from the ocean. Antibiotic susceptibility tests showed that the strain is resistant to all tested antibiotics except fluorine quinolones. Genomic sequence information indicates total length of genomic sequence is 6,131,579bp, G+ C% accounted for 41.94%. Resistance gene analysis predicted 10 antibiotics resistant genes which are strict matching, these genes are associated with drug resistance efflux pump genes and antibiotic target modification enzyme genes.Two novel marine bacteria were isolated, polyphasic taxonomy method was performed in this study to identify the taxonomic status. The results show that FA028T should be classified as representing a novel species of a new genus within the family Alteromonadaceae, for which the name Alkalimarinus sediminis gen. nov. sp. nov. was proposed. The type strain of Alkalimarinus sediminis is FA028T (= CICC 10906T= KCTC 42258T); NH1T should be classified as representing a novel species within the genus Algoriphagus, for which the name Algoriphagus resistens sp. nov. was proposed(Algoriphagus resistens sp. nov.); The type strain of Algoriphagus resistens is NH1T (= KCTC 42258T).