关键词: blaIMP-19 chromosomal encoded carbapenemase integron phage whole-genome sequencing

Mesh : Acinetobacter baumannii / genetics drug effects enzymology Plasmids / genetics Integrons / genetics Humans Acinetobacter Infections / microbiology beta-Lactamases / genetics metabolism Anti-Bacterial Agents / pharmacology Bacterial Proteins / genetics metabolism Drug Resistance, Multiple, Bacterial / genetics Taiwan Microbial Sensitivity Tests Whole Genome Sequencing Bacteriophages / genetics enzymology Chromosomes, Bacterial / genetics Carbapenems / pharmacology Multilocus Sequence Typing Bacteremia / microbiology

来  源:   DOI:10.1128/spectrum.00382-24

Abstract:
Integration of carbapenemase gene blaIMP into the chromosome of carbapenem-resistant Acinetobacter baumannii (CRAB) has not been reported. The aim of this study was to explore the genomic characteristics of CRAB AB322 isolated from a Taiwanese patient diagnosed with bacteremia in 2011, whose chromosome harbors blaIMP-19. Disk diffusion and broth microdilution were employed to analyze the antimicrobial susceptibility of AB322 to 14 antimicrobials. Nanopore whole-genome sequencing platform was utilized for AB322 genome sequencing, and conjugation was further performed to investigate the transferability of blaIMP-19 to amikacin-resistant A. baumannii 218 (AB218) and Acinetobacter nosocomialis 254 (AN254). The results showed that AB322 was classified as multidrug-resistant A. baumannii but remained susceptible to ampicillin/sulbactam, colistin, and tigecycline. Whole-genome sequencing revealed the AB322 genome, consisting of a 4,098,985-bp chromosome, a 71,590-bp conjugative plasmid named pAB322-1, and an 8,726-bp plasmid named pAB322-2. Multilocus sequence typing analysis indicated that AB322 belonged to sequence type 1. AB322 chromosome harbored numerous acquired antimicrobial resistance genes, including aph(3\')-Ia, aadA1b, aadA1, aac(6\')-Ib3, aac (3)-Ia, blaADC-25, blaOXA-69, blaIMP-19, catA1, sul1, and tet(A), conferring resistance to β-lactams, aminoglycosides, chloramphenicol, sulfamethoxazole, and tetracyclines. Moreover, blaIMP-19 was identified to be situated within class 1 integron In240 and an incomplete PHAGE_Salmon_SJ46_NC_031129 on AB322 chromosome. However, conjugation experiments revealed that blaIMP-19 could not be transferred to AB218 and AN254 in our testing conditions. In conclusion, we first report the presence of chromosomal-integrated blaIMP-19 in CRAB, possibly mediated by integron. The future dissemination of blaIMP-19 among different species, leading to carbapenem resistance dissemination, requires close monitoring.
OBJECTIVE: The horizontal transfer of antimicrobial-resistant genes is crucial for the dissemination of resistance, especially as Acinetobacter baumannii has emerged as a clinically significant pathogen. However, in this study, we first report the integration of the blaIMP-19 gene into the chromosome of A. baumannii, and such horizontal transfer may be associated with integron-phage elements. Additionally, it is possible that these DNA fragments carrying antimicrobial-resistant genes could further spread to other pathogens by moving horizontally onto conjugative plasmids.
摘要:
碳青霉烯酶基因blaIMP整合到碳青霉烯耐药鲍曼不动杆菌(CRAB)的染色体中尚未见报道。这项研究的目的是探索从2011年诊断为菌血症的台湾患者中分离出的CRABAB322的基因组特征,该患者的染色体带有blaIMP-19。采用圆盘扩散和肉汤微量稀释来分析AB322对14种抗菌剂的抗菌敏感性。利用纳米孔全基因组测序平台进行AB322基因组测序,并进一步进行结合以研究blaIMP-19对阿米卡星耐药的鲍曼不动杆菌218(AB218)和医院不动杆菌254(AN254)的转移性。结果表明,AB322被归类为多重耐药鲍曼不动杆菌,但对氨苄西林/舒巴坦仍然敏感。粘菌素,还有替加环素.全基因组测序揭示了AB322基因组,由4,098,985bp的染色体组成,一个名为pAB322-1的71,590-bp接合质粒和一个名为pAB322-2的8,726-bp质粒。多位点序列分型分析表明,AB322属于1型序列。AB322染色体包含许多获得性抗菌素抗性基因,包括aph(3')-Ia,aadA1b,aadA1,aac(6')-Ib3,aac(3)-Ia,blaADC-25、blaOXA-69、blaIMP-19、catA1、sul1和tet(A),赋予β-内酰胺抗性,氨基糖苷类,氯霉素,磺胺甲恶唑,还有四环素.此外,blaIMP-19被鉴定为位于AB322染色体上的1类整合子In240和不完整的PHAGE_Salmon_SJ46_NC_031129内。然而,结合实验表明,在我们的测试条件下,blaIMP-19不能转移到AB218和AN254中。总之,我们首先报道了CRAB中染色体整合的blaIMP-19的存在,可能由整合子介导。blaIMP-19在不同物种中的未来传播,导致碳青霉烯耐药性传播,需要密切监测。
目的:抗菌素耐药基因的水平转移对于耐药性的传播至关重要,特别是鲍曼不动杆菌已成为临床上重要的病原体。然而,在这项研究中,我们首先报道了blaIMP-19基因整合到鲍曼不动杆菌的染色体中,这种水平转移可能与整合子-噬菌体元件有关。此外,这些携带抗微生物药物抗性基因的DNA片段可能通过水平移动到接合质粒上而进一步传播到其他病原体。
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