Choi Yujin, Lee Ji-Young, Lee Haejeong, Park Myungseo, Kang KyeongJin, Lim Suk-Kyung, Shin Dongwoo, Ko Kwan Soo
Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
Division of Antimicrobial Resistance, Korea Centers for Disease Control and Prevention, Cheongju, South Korea.
Front Microbiol. 2020 May 13;11:798. doi: 10.3389/fmicb.2020.00798. eCollection 2020.
Five types of strains were obtained and sequenced: colistin-susceptible (CL-S) strains, induced colistin-resistant (CL-IR) strains, negative colistin-resistant strains from livestock (CL-chrR), -positive colistin-resistant strains (CL-mcrR), and -transferred transconjugants (TC-mcr). Amino acid alterations of PmrAB, PhoPQ, and EptA were identified, and their mRNA expression was measured. Their growth rate was evaluated, and an competition assay was performed. Virulence was compared through serum resistance and survival in macrophages and . CL-IR and CL-chrR strains were colistin-resistant due to amino acid alterations in PmrAB, PhoPQ, or EptA, and their overexpression. All colistin-resistant strains did not show reduced growth rates compared with CL-S strains. CL-IR and CL-chrR strains were less competitive than the susceptible strain, but CL-mcrR strains were not. In addition, TC-mcr strains were also significantly more competitive than their respective parental susceptible strain. CL-IR strains had similar or decreased survival rates in human serum, macrophages, and fruit flies, compared with their parental, susceptible strains. CL-chrR strains were also less virulent than CL-S strains. Although CL-mcrR strains showed similar survival rates in human serum and fruit fly to CL-S strains, the survival rates of TC-mcr strains decreased significantly in human serum, macrophages, and fruit flies, compared with their susceptible recipient strain (J53). Chromosome-mediated, colistin-resistant strains have a fitness cost, but plasmids bearing do not increase the fitness burden of . Along with high usage of polymyxins, the no fitness cost of -positive strains may facilitate rapid spread of colistin resistance.
黏菌素敏感(CL-S)菌株、诱导型黏菌素耐药(CL-IR)菌株、来自家畜的阴性黏菌素耐药菌株(CL-chrR)、阳性黏菌素耐药菌株(CL-mcrR)以及转移接合子(TC-mcr)。鉴定了PmrAB、PhoPQ和EptA的氨基酸改变,并测量了它们的mRNA表达。评估了它们的生长速率,并进行了竞争试验。通过血清抗性以及在巨噬细胞中的存活情况比较了毒力。CL-IR和CL-chrR菌株由于PmrAB、PhoPQ或EptA中的氨基酸改变及其过表达而对黏菌素耐药。与CL-S菌株相比,所有黏菌素耐药菌株的生长速率均未降低。CL-IR和CL-chrR菌株的竞争力低于敏感菌株,但CL-mcrR菌株并非如此。此外,TC-mcr菌株的竞争力也明显高于其各自的亲本敏感菌株。与亲本敏感菌株相比,CL-IR菌株在人血清、巨噬细胞和果蝇中的存活率相似或降低。CL-chrR菌株的毒力也低于CL-S菌株。尽管CL-mcrR菌株在人血清和果蝇中的存活率与CL-S菌株相似,但与敏感受体菌株(J53)相比,TC-mcr菌株在人血清、巨噬细胞和果蝇中的存活率显著降低。染色体介导的黏菌素耐药菌株存在适应性代价,但携带mcr的质粒不会增加其适应性负担。随着多黏菌素的大量使用,mcr阳性菌株无适应性代价可能会促进黏菌素耐药性的快速传播。