P-216CM

WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. Exploitation of this process allowed the synthesis of eleven alanine-scanning analogues and eight lysine-scanning analogues. The antimicrobial activity of these analogues was evaluated in vitro against Gram-positive bacteria. Based on the MIC results, a primary systematic structure-activity relationship has been established.

A multidrug-resistant Morganella morganii strain (CQ-M7), isolated from the kidney of a diseased Chinese giant salamander in China, was examined with whole genome sequencing to better understand drug tolerance and its pathogenicity.

The draft genome of the investigated strain was assembled using HGA assembler and annotated using Rapid Annotations Subsystems Technology (RAST) server. The contigs were annotated by the appropriate bioinformatics tools available on the National Center for Biotechnology Information (NCBI) website. Antibiotic resistance genes were detected by PCR. Pathogenicity of the isolate was performed on 30 healthy Chinese giant salamanders with different infection dosages.

The CQ-M7 strain showed resistance to multiple antimicrobials, especially to aminoglycoside and β-lactam antibiotics. Seventeen drug-resistance genes were detected, which were related to β-lactams, aminoglycosides, fluoroquinolones, tetracyclines, peptide antibiotic, and fosfomycin resistance. Sequence analysis showed the assembled genome size to be 4 966 326bp with 51.16% of GC content, containing 4587 protein-coding genes, 71 pseudogenes, five rRNAs, 80 tRNAs, and five noncoding RNAs. The genome sequence was deposited in GenBank under accession number RQIJ00000000. Artificial infection results indicated that the CQ-M7 strain was a low-virulence strain for the Chinese giant salamander.

It is believed that this is the first draft genome of Chinese giant salamander original Morganella morganii strain harbouring multiple antibiotic resistance genes in China. The reported genome sequence could provide insights into antibiotic resistance mechanisms and control strategies of Morganella morganii.