Uz Zaman Taher, Albladi Maha, Siddique Mohammed Ismail, Aljohani Sameera M, Balkhy Hanan H
Infectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia,
Deccan College of Medical Sciences, Hyderabad, India.
Infect Drug Resist. 2018 Aug 15;11:1183-1187. doi: 10.2147/IDR.S161146. eCollection 2018.
In and components of pmrHFIJKLM operon play a major role in colistin resistance.
We analyzed 23 nonduplicating colistin-resistant isolates, collected during the years 2011-2015, for the possible mechanism underlying their nonsusceptibility to colistin. Isolates were tested for their minimum inhibitory concentrations and antibiotic resistance determinants and genotyped by multilocus sequence typing (MLST). The MLST genes, antibiotic-resistant genes, and the genes of two component system (TCS), including , and , were investigated by PCR amplification and Sanger sequencing.
All isolates were distributed in eight sequence types (STs) and showed mutations either in B or PhoP genes. ISKpn14 was found in 10, ISKpn28 in four, and IS903 in three isolates. One isolate showed deletion of a single nucleotide in B open reading frame causing premature stop codon. L26Q substitution in PhoP was found in five isolates.
The mutations in B were mostly mediated by insertion elements (IS). ISKpn14 is the major IS while ISKpn28 is reported for the first time in mediating B disruption. IS903, an IS5 family member, involved in B disruption in three ST-152 NDM-1-positive isolates, was previously responsible for -36 disruption in our carbapenem-resistant and appears to contribute to transform the isolates into a pan-drug ones. Also, the abundance of insertion sites in B indicates the plasticity of this gene. In our isolates, IS-mediated colistin resistance appears to be a later phenomenon than mutation in gene.
pmrHFIJKLM操纵子的基因和元件在多粘菌素耐药性中起主要作用。
我们分析了2011年至2015年期间收集的23株非重复的耐多粘菌素分离株，以探究其对多粘菌素不敏感的潜在机制。对分离株进行最低抑菌浓度和抗生素耐药决定因素检测，并通过多位点序列分型（MLST）进行基因分型。通过PCR扩增和桑格测序研究MLST基因、抗生素耐药基因以及双组分系统（TCS）的基因，包括 和 。
所有分离株分布在8种序列类型（STs）中，并且在B或PhoP基因中显示出突变。在10株分离株中发现了ISKpn14，4株中发现了ISKpn28，3株中发现了IS903。一株分离株在B开放阅读框中显示单核苷酸缺失，导致提前终止密码子。在5株分离株中发现PhoP中的L26Q替换。
B中的突变大多由插入元件（IS）介导。ISKpn14是主要的IS，而ISKpn28首次被报道介导B破坏。IS903是IS5家族成员，在3株ST-152 NDM-1阳性分离株中参与B破坏，此前在我们的耐碳青霉烯类 中导致 -36破坏，似乎有助于将分离株转变为泛耐药株。此外，B中插入位点的丰富表明该基因的可塑性。在我们的分离株中，IS介导的多粘菌素耐药性似乎是比 基因突变更晚出现的现象。
