Cholera remains a formidable disease, and reports of multidrug-resistant strains of the causative agent Vibrio cholerae have become common during the last 3 decades. The pervasiveness of resistance determinants has largely been ascribed to mobile genetic elements, including SXT/R391 integrative conjugative elements, IncC plasmids, and genomic islands (GIs). Conjugative transfer of IncC plasmids is activated by the master activator AcaCD whose regulatory network extends to chromosomally integrated GIs. MGIVchHai6 is a multidrug resistance GI integrated at the 3′ end of trmE (mnmE or thdF) in chromosome 1 of non-O1/non-O139 V. cholerae clinical isolates from the 2010 Haitian cholera outbreak. In the presence of an IncC plasmid expressing AcaCD, MGIVchHai6 excises from the chromosome and transfers at high frequency. Herein, the mechanism of mobilization of MGIVchHai6 GIs by IncC plasmids was dissected. Our results show that AcaCD drives expression of GI-borne genes, including xis and mobI_M, involved in excision and mobilization. A 49-bp fragment upstream of mobI_M was found to serve as the minimal origin of transfer (oriT) of MGIVchHai6. The direction of transfer initiated at oriT was determined using IncC plasmid-driven mobilization of chromosomal markers via MGIVchHai6. In addition, IncC plasmid-encoded factors, including the relaxase TraI, were found to be required for GI transfer. Finally, in silico exploration of Gammaproteobacteria genomes identified 47 novel related and potentially AcaCD-responsive GIs in 13 different genera. Despite sharing conserved features, these GIs integrate at trmE, yicC, or dusA and carry a diverse cargo of genes involved in phage resistance.

中文翻译：

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霍乱弧菌的抗生素耐药性：来自 IncC 质粒介导的在 trmE 插入的新基因组岛家族的传播的机制见解。

霍乱仍然是一种可怕的疾病，在过去的 30 年中，关于病原体霍乱弧菌的多重耐药菌株的报道变得普遍。抗性决定因素的普遍性在很大程度上归因于可移动的遗传元件，包括 SXT/R391 整合结合元件、IncC 质粒和基因组岛 (GI)。IncC 质粒的接合转移由主激活剂 AcaCD 激活，其调节网络扩展到染色体整合的 GI。MGI Vch Hai6 是一种多药耐药 GI，整合在非 O1/非 O139霍乱弧菌1 号染色体trmE（mnmE或thdF）的 3' 末端2010 年海地霍乱爆发的临床分离株。在表达 AcaCD 的 IncC 质粒存在的情况下，MGI Vch Hai6 从染色体上切除并高频转移。在此，剖析了 IncC 质粒对 MGI Vch Hai6 GIs的动员机制。我们的研究结果表明，GI-源性基因，包括AcaCD驱动表达XIS和摩比_中号，涉及切除和动员。发现mobI _M上游的 49 bp 片段作为MGI Vch Hai6的最小转移起点 ( oriT ) 。在oriT发起的转移方向通过 MGI Vch Hai6使用 IncC 质粒驱动的染色体标记动员确定。此外，发现 GI 转移需要 IncC 质粒编码因子，包括松弛酶 TraI。最后，对Gammaproteobacteria基因组的计算机探索在 13 个不同属中鉴定了 47 个新的相关和潜在的 AcaCD 响应 GI。尽管共享保守特征，但这些 GI 在trmE、yicC或dusA处整合，并携带多种参与噬菌体抗性的基因。