Abundance of Colistin-Resistant, OXA-23-and ArmA-Producing Acinetobacter baumannii Belonging to International Clone 2 in Greece
Abundance of Colistin-Resistant, OXA-23-and ArmA-Producing Acinetobacter baumannii Belonging to International Clone 2 in Greece
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DOI：
10.3389/fmicb.2020.00668
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发表时间：
2020-04-15
影响因子：
5.2
通讯作者：
van Belkum, Alex
中科院分区：
文献类型：
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作者：
Palmieri, Mattia;D'Andrea, Marco Maria;van Belkum, Alex
碳青霉烯类耐药鲍曼不动杆菌（CRAB）是临床环境中最具挑战性的病原体之一。粘菌素通常用于治疗该病原体的感染，但已报道粘菌素耐药性增加。我们在2015年至2017年期间从9家希腊医院获得了122株CRAB分离株，对其中的粘菌素耐药株（ColR; N = 40，32.8%）进行了全基因组测序，还包括两株粘菌素敏感株（ColS）进行了比较。所有ColR分离株的特征在于先前描述的突变，PmrB（A226 V），这是与低水平的粘菌素耐药。一些分离株的特征在于PmrB（E140 V或L178 F）或PmrA（K172 I或D10 N）中的额外突变，本文首次描述，以及更高的粘菌素最低抑制浓度（MIC），高达64 mg/L。脂质A的质谱分析显示脂质A上存在磷酸乙醇胺（pEtN）部分，可能是由PmrA/B诱导的pmrC过表达引起的。有趣的是，两种ColS分离株也具有相同的脂质A修饰，表明并非所有脂质A修饰都会导致粘菌素抗性，或者其他因素可能有助于抗性表型。大多数分离株（N = 37，92.5%）属于全球分布的国际克隆（IC）2，并包含4种不同的序列类型（ST），如使用牛津方案（ST 425，208，451和436）定义的。3个菌株属于IC 1和ST 1567。所有基因组均含有一个内源性bla（OXA-51）组碳青霉烯酶基因，其中bla（OXA-66）和bla（OXA-69）分别与IC 2和IC 1相关。碳青霉烯耐药是由于最常报告的获得性碳青霉烯酶基因bla（OXA-23），ISAba 1位于该基因上游，可能增加其表达。在87.5%的分离株中检测到与氨基糖苷类高水平耐药相关的阿尔马基因。总的来说，这些结果揭示了不同克隆谱系朝向相同的粘菌素抗性机制的趋同进化，从而限制了用于治疗CRAB感染的有效治疗选择。
Carbapenem resistant Acinetobacter baumannii (CRAB) represents one of the most challenging pathogens in clinical settings. Colistin is routinely used for treatment of infections by this pathogen, but increasing colistin resistance has been reported. We obtained 122 CRAB isolates from nine Greek hospitals between 2015 and 2017, and those colistin resistant (ColR; N = 40, 32.8%) were whole genome sequenced, also by including two colistin susceptible (ColS) isolates for comparison. All ColR isolates were characterized by a previously described mutation, PmrB(A226V), which was associated with low-level colistin resistance. Some isolates were characterized by additional mutations in PmrB (E140V or L178F) or PmrA (K172I or D10N), first described here, and higher colistin minimum inhibitory concentrations (MICs), up to 64 mg/L. Mass spectrometry analysis of lipid A showed the presence of a phosphoethanolamine (pEtN) moiety on lipid A, likely resulting from the PmrA/B-induced pmrC overexpression. Interestingly, also the two ColS isolates had the same lipid A modification, suggesting that not all lipid A modifications lead to colistin resistance or that other factors could contribute to the resistance phenotype. Most of the isolates (N = 37, 92.5%) belonged to the globally distributed international clone (IC) 2 and comprised four different sequence types (STs) as defined by using the Oxford scheme (ST 425, 208, 451, and 436). Three isolates belonged to IC1 and ST1567. All the genomes harbored an intrinsic bla(OXA-51) group carbapenemase gene, where bla(OXA-66) and bla(OXA-69) were associated with IC2 and IC1, respectively. Carbapenem resistance was due to the most commonly reported acquired carbapenemase gene bla(OXA-23), with ISAba1 located upstream of the gene and likely increasing its expression. The armA gene, associated with high-level resistance to aminoglycosides, was detected in 87.5% of isolates. Collectively, these results revealed a convergent evolution of different clonal lineages toward the same colistin resistance mechanism, thus limiting the effective therapeutic options for the treatment of CRAB infections.