華中農(nóng)業(yè)大學(xué)揭示水產(chǎn)養(yǎng)殖中抗生素誘導(dǎo)的多重耐藥基因轉(zhuǎn)移模式

　　近日，華中農(nóng)業(yè)大學(xué)生命科學(xué)技術(shù)學(xué)院益生菌智造創(chuàng)新團(tuán)隊(duì)聯(lián)合信息學(xué)院鄭金水副教授在抗性基因傳播方面的研究成果以“Enrofloxacin-induced transfer of multiple-antibiotic resistance genes and emergence of novel resistant bacteria in red swamp crayfish guts and pond sediments ”為題在Journal of Hazardous Materials上發(fā)表。本研究揭示了在抗生素壓力下抗性基因（ARGs）的選擇性擴(kuò)增和傳遞以及ARGs與宿主細(xì)菌的相關(guān)性，并基于腸道和沉積物中的微生物群的宏基因組序列重建了新的多重耐藥細(xì)菌基因組。

 

　　抗生素耐藥基因（ARGs）可以從環(huán)境微生物轉(zhuǎn)移到人類病原微生物，從而導(dǎo)致細(xì)菌感染治療失敗，特別是對(duì)多種抗生素具有耐藥性的致病菌感染是死亡率的重要原因。水產(chǎn)養(yǎng)殖系統(tǒng)因?yàn)榕c水、沉積物和其他生態(tài)系統(tǒng)有著廣泛的聯(lián)系，抗生素在其的應(yīng)用為耐藥性的傳播提供了一個(gè)廣泛的環(huán)境途徑。然而，在抗生素暴露的水產(chǎn)養(yǎng)殖系統(tǒng)中，ARGs的來源、歷時(shí)變化和流動(dòng)性仍然不清楚。本研究以小龍蝦養(yǎng)殖為模型，分析了人工給藥后（第三代喹諾酮類藥物恩諾沙星）（1）小龍蝦腸道和底泥各種ARG的時(shí)間變化，（2）小龍蝦腸道和沉積物中細(xì)菌之間ARG轉(zhuǎn)移的機(jī)制，（3）ARG與宿主細(xì)菌之間的相互作用，以確定耐藥基因偏愛的細(xì)菌。

 

　　研究結(jié)果表明，恩諾沙星的應(yīng)用不僅增加了喹諾酮類耐藥ARGs的相對(duì)豐度，而且促進(jìn)了對(duì)其他抗生素耐藥ARGs的出現(xiàn)。此外，抗生素的應(yīng)用誘導(dǎo)ARGs通過水平基因轉(zhuǎn)移（HGT）在小龍蝦腸道細(xì)菌和沉積物細(xì)菌中傳播。值得注意的是，在抗生素壓力下，轉(zhuǎn)座酶介導(dǎo)的重組是ARGs轉(zhuǎn)移的主要驅(qū)動(dòng)因素。腸桿菌科可能是自然界中一個(gè)流動(dòng)的ARG庫，匯集了不同來源的ARG。研究還表明，恩諾沙星的應(yīng)用誘導(dǎo)了一些攜帶多種ARGs的新型抗生素耐藥物種。這些攜帶ARGs的細(xì)菌對(duì)水生動(dòng)物和環(huán)境的污染值得高度關(guān)注。該研究強(qiáng)調(diào)了抗生素應(yīng)用引起的ARG通過HGT在養(yǎng)殖環(huán)境中傳播的風(fēng)險(xiǎn)。研究結(jié)果可為抗生素耐藥性管理提供參考。

 

　　生命科學(xué)技術(shù)學(xué)院博士研究生金雪霞為論文第一作者，彭楠教授、鄭金水教授為通訊作者。同時(shí)課題組劉思真、劉通等研究生參與了研究。本研究得到了湖北洪山實(shí)驗(yàn)室重大項(xiàng)目和生科院龍?jiān)朴?jì)劃等支持。

 

　　【英文摘要】

 

　　Antibiotic resistance genes （ARGs） can be transferred from environmental microbes to human pathogens, thus leading to bacterial infection treatment failures. The aquaculture polluted by over-used antibiotics is considered as a notorious reservoir of ARGs. However, the origin, diachronic changes, and mobility of ARGs under antibiotic exposure in aquaculture systems remain elusive. Our findings showed that enrofloxacin application also increased the relative abundance of various ARGs in addition to quinolone-resistance genes and induced ARG dissemination in crayfish gut and sediment bacteria. Further investigation indicated that the transposase-mediated recombination was the major driver of horizontal gene transfer （HGT） of ARGs under antibiotic stress. Notably, enrofloxacin application also induced the generation of some metagenome-assembled genomes （MAGs） carrying multiple ARGs, which were identified as novel species. Additionally, Enterobacteriaceae constituted a mobile ARG pool in aquaculture. Therefore, aquaculture provides potential wide environmental pathways for generation and spread of antibiotic resistance. Our findings of ARG temporal variations and dissemination pattern in aquaculture with artificial use of antibiotics are critical to the management of antibiotic resistance, which is of great ecosystem and health implications.

 

　　論文連接：https://doi.org/10.1016/j.jhazmat.2022.130261