Ogawara Hiroshi
HO Bio Institute, 33-9, Yushima-2, Bunkyo-ku, Tokyo 113-0034, Japan.
Department of Biochemistry, Meiji Pharmaceutical University, 522-1, Noshio-2, Kiyose, Tokyo 204-8588, Japan.
Molecules. 2019 Sep 21;24(19):3430. doi: 10.3390/molecules24193430.
Antibiotic resistance poses a tremendous threat to human health. To overcome this problem, it is essential to know the mechanism of antibiotic resistance in antibiotic-producing and pathogenic bacteria. This paper deals with this problem from four points of view. First, the antibiotic resistance genes in producers are discussed related to their biosynthesis. Most resistance genes are present within the biosynthetic gene clusters, but some genes such as paromomycin acetyltransferases are located far outside the gene cluster. Second, when the antibiotic resistance genes in pathogens are compared with those in the producers, resistance mechanisms have dependency on antibiotic classes, and, in addition, new types of resistance mechanisms such as Eis aminoglycoside acetyltransferase and self-sacrifice proteins in enediyne antibiotics emerge in pathogens. Third, the relationships of the resistance genes between producers and pathogens are reevaluated at their amino acid sequence as well as nucleotide sequence levels. Pathogenic bacteria possess other resistance mechanisms than those in antibiotic producers. In addition, resistance mechanisms are little different between early stage of antibiotic use and the present time, e.g., β-lactam resistance in . Lastly, guanine + cytosine (GC) barrier in gene transfer to pathogenic bacteria is considered. Now, the resistance genes constitute resistome composed of complicated mixture from divergent environments.
抗生素耐药性对人类健康构成了巨大威胁。为克服这一问题,了解抗生素产生菌和病原菌中的抗生素耐药机制至关重要。本文从四个角度探讨了这一问题。首先,讨论了产生菌中与抗生素生物合成相关的耐药基因。大多数耐药基因存在于生物合成基因簇内,但有些基因如巴龙霉素乙酰转移酶位于基因簇之外很远的地方。其次,将病原菌中的抗生素耐药基因与产生菌中的进行比较时,耐药机制因抗生素类别而异,此外,病原菌中还出现了新型耐药机制,如埃希氏菌属氨基糖苷乙酰转移酶和烯二炔类抗生素中的自我牺牲蛋白。第三,在氨基酸序列和核苷酸序列水平上重新评估了产生菌和病原菌中耐药基因之间的关系。病原菌拥有与抗生素产生菌不同的其他耐药机制。此外,抗生素使用早期和目前的耐药机制差异不大,例如,β-内酰胺耐药性在……最后,考虑了基因转移至病原菌过程中的鸟嘌呤+胞嘧啶(GC)屏障。现在,耐药基因构成了由来自不同环境的复杂混合物组成的耐药基因组。