Sheikhalizadeh Vajihe, Hasani Alka, Ahangarzadeh Rezaee Mohammad, Rahmati-Yamchi Mohammad, Hasani Akbar, Ghotaslou Reza, Goli Hamid Reza
Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
J Infect Chemother. 2017 Feb;23(2):74-79. doi: 10.1016/j.jiac.2016.09.012. Epub 2016 Nov 23.
Therapeutic resistance towards most of the current treatment regime by Acinetobacter baumannii has reduced the prescribing antibiotic pattern and option is being re-shifted towards more toxic agents including aminoglycosides. The present investigation aimed at to study various mechanisms towards aminoglycoside non-susceptibility in clinical isolates of A. baumannii. The bacteria were subjected to genetic basis assessment for the presence of aminoglycoside modifying enzymes (AME), 16S rRNA methylase encoding genes and relative expression of AdeABC and AbeM efflux pumps in relation to their susceptibility to five aminoglycosides. When isolates were subjected to typing by repetitive extragenic palindromic (REP) PCR, isolates could be separated into thirteen definite clones. The majority of isolates (94%) were positive for AME encoding genes. Possession of ant(2')-Ia correlated with non-susceptibility towards gentamicin, amikacin, kanamycin, tobramycin; while, presence of aph(3')-VIa attributed to resistance towards amikacin, kanamycin; possession of aac(3')-Ia allied with non-susceptibility to amikacin, tobramycin and presence of aac(3')IIa correlated with kanamycin non-susceptibility. Presence of armA was detected in 34.4%, 34.2%, 29.2%, 40.3%, and 64.2% of isolates showing non-susceptibility to gentamicin, amikacin, kanamycin, tobramycin and netilmicin, respectively. No isolates were found to carry rmtB or rmtC. Amikacin non-susceptibility in comparison to other aminoglycosides correlated with over production of adeB. Overall, the results represented a definitive correlation between presence of AME encoding genes as well as armA and resistance of A. baumannii towards aminoglycosides. On the other hand, the up-regulation of AdeABC and AbeM systems was found to have only the partial role in development of aminoglycoside resistance.
鲍曼不动杆菌对当前大多数治疗方案产生的治疗抗性，已经改变了抗生素的处方模式，并且选择正再次转向包括氨基糖苷类在内的毒性更强的药物。本研究旨在探究鲍曼不动杆菌临床分离株对氨基糖苷类不敏感的各种机制。对这些细菌进行了遗传基础评估，检测氨基糖苷类修饰酶（AME）、16S rRNA甲基化酶编码基因的存在情况，以及AdeABC和AbeM外排泵相对于它们对五种氨基糖苷类药物敏感性的相对表达。当通过重复外显子回文序列（REP）PCR对分离株进行分型时，分离株可被分为13个明确的克隆。大多数分离株（94%）的AME编码基因呈阳性。携带ant(2')-Ia与对庆大霉素、阿米卡星、卡那霉素、妥布霉素不敏感相关；而aph(3')-VIa的存在导致对阿米卡星、卡那霉素耐药；携带aac(3')-Ia与对阿米卡星、妥布霉素不敏感相关，aac(3')IIa的存在与对卡那霉素不敏感相关。在对庆大霉素、阿米卡星、卡那霉素、妥布霉素和奈替米星不敏感的分离株中，分别检测到34.4%、34.2%、29.2%、40.3%和64.2%的armA。未发现分离株携带rmtB或rmtC。与其他氨基糖苷类药物相比，阿米卡星不敏感与adeB的过量产生相关。总体而言，结果表明AME编码基因以及armA的存在与鲍曼不动杆菌对氨基糖苷类药物的耐药性之间存在明确的相关性。另一方面，发现AdeABC和AbeM系统的上调在氨基糖苷类耐药性的发展中仅起部分作用。
