Intercellular Transfer of Chromosomal Antimicrobial Resistance Genes between Acinetobacter baumannii Strains Mediated by Prophages
Intercellular Transfer of Chromosomal Antimicrobial Resistance Genes between Acinetobacter baumannii Strains Mediated by Prophages
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DOI：
10.1128/aac.00334-19
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发表时间：
2019-05
影响因子：
4.9
通讯作者：
J. Wachino;Wanchun Jin;K. Kimura;Y. Arakawa
中科院分区：
文献类型：
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作者：
J. Wachino;Wanchun Jin;K. Kimura;Y. Arakawa
抗微生物药物耐药性基因（ARGs）在包括鲍曼不动杆菌在内的革兰氏阴性病原体中的传播主要是由可转移质粒介导的；然而，ARGs经常被整合到染色体中。ARG如何横向整合到鲍曼不动杆菌的染色体中，以及它是否作为ARG进一步传播的原因，目前仍不清楚。在这里，我们证明了鲍曼不动杆菌中染色体ARGs的细胞间噬菌体介导的转移没有直接的细胞间相互作用。抗微生物药物耐药性基因（ARGs）在包括鲍曼不动杆菌在内的革兰氏阴性病原体中的传播主要是通过可转移质粒介导的；然而，ARGs经常被整合到染色体中。ARG如何横向整合到鲍曼不动杆菌的染色体中，以及它是否作为ARG进一步传播的原因，目前仍不清楚。在这里，我们证明了鲍曼不动杆菌中染色体ARGs的细胞间噬菌体介导的转移没有直接的细胞间相互作用。我们从多药耐药（MDR）鲍曼不动杆菌NU-60培养上清中制备了含有arg的细胞外DNA （eDNA）组分，并将抗菌敏感（AS）鲍曼不动杆菌ATCC 17978暴露于eDNA组分中。抗菌素耐药（AR）鲍曼不动杆菌ATCC 17978衍生物似乎通过同源重组获得了多种ARGs，这些ARGs来自MDR鲍曼不动杆菌染色体的分散位点及其周围区域，包括armA（氨基糖苷抗性）、blatem1 （β-内酰胺抗性）、tet(B)（四环素抗性）和gyrA-81L（萘啶酸抗性）基因。值得注意的是，赋予抗菌素耐药性的edna被包裹在由噬菌体颗粒组成的特定衣壳蛋白中，从而保护edna免受洗涤剂和dna酶的处理。含有ARGs的噬菌体可能从耐多药鲍曼不动杆菌释放到细胞外空间，从而将ARGs转导为鲍曼不动杆菌，导致受体获得AR特性。我们的结论是，噬菌体能够携带随机片段鲍曼不动杆菌基因组dna的广义转导，使鲍曼不动杆菌菌株之间的染色体ARGs在细胞间有效转移，而无需直接的细胞间相互作用。
The spread of antimicrobial resistance genes (ARGs) among Gram-negative pathogens, including Acinetobacter baumannii, is primarily mediated by transferable plasmids; however, ARGs are frequently integrated into its chromosome. How ARG gets horizontally incorporated into the chromosome of A. baumannii, and whether it functions as a cause for further spread of ARG, remains unknown. Here, we demonstrated intercellular prophage-mediated transfer of chromosomal ARGs without direct cell-cell interaction in A. baumannii. ABSTRACT The spread of antimicrobial resistance genes (ARGs) among Gram-negative pathogens, including Acinetobacter baumannii, is primarily mediated by transferable plasmids; however, ARGs are frequently integrated into its chromosome. How ARG gets horizontally incorporated into the chromosome of A. baumannii, and whether it functions as a cause for further spread of ARG, remains unknown. Here, we demonstrated intercellular prophage-mediated transfer of chromosomal ARGs without direct cell-cell interaction in A. baumannii. We prepared ARG-harboring extracellular DNA (eDNA) components from the culture supernatant of a multidrug-resistant (MDR) A. baumannii NU-60 strain and exposed an antimicrobial-susceptible (AS) A. baumannii ATCC 17978 strain to the eDNA components. The antimicrobial-resistant (AR) A. baumannii ATCC 17978 derivatives appeared to acquire various ARGs, originating from dispersed loci of the MDR A. baumannii chromosome, along with their surrounding regions, by homologous recombination, with the ARGs including armA (aminoglycoside resistance), blaTEM-1 (β-lactam resistance), tet(B) (tetracycline resistance), and gyrA-81L (nalidixic acid resistance) genes. Notably, the eDNAs conferring antimicrobial resistance were enveloped in specific capsid proteins consisting of phage particles, thereby protecting the eDNAs from detergent and DNase treatments. The phages containing ARGs were likely released into the extracellular space from MDR A. baumannii, thereby transducing ARGs into AS A. baumannii, resulting in the acquisition of AR properties by the recipient. We concluded that the generalized transduction, in which phages were capable of carrying random pieces of A. baumannii genomic DNAs, enabled efficacious intercellular transfer of chromosomal ARGs between A. baumannii strains without direct cell-cell interaction.