Farshadzadeh Zahra, Khoshnood Saeed, Akrami Sousan, Abbasi Montazeri Effat, Moradi Melika, Masihzadeh Sara, Daneshfar Sara, Navidifar Tahereh
Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Arch Microbiol. 2025 May 25;207(7):153. doi: 10.1007/s00203-025-04347-7.
This study investigated the gene expression pattern of resistance-nodulation-division (RND) efflux pumps, in Acinetobacter baumannii isolates with a focus on their association with carbapenem resistance and biofilm formation ability. A collection of 102 A. baumannii isolates was evaluated for antibiotic susceptibility testing using an automated broth microdilution technique. The ability of these isolates to form biofilms was evaluated using a standardized protocol. The isolates were genotyped using the Multiple-Locus Variable number tandem repeat Analysis-8 (MLVA-8) method and the gene expression levels of the RND efflux pump genes were quantified by real-time PCR. Results showed widespread antibiotic resistance, with 85% of isolates classified as multidrug resistant. Genotyping results identified 32 different MLVA types organized into six clusters (A-F) and 17 unique genotypes. The majority of isolates demonstrated the ability to form biofilms, and an inverse relationship was observed between biofilm formation and carbapenem resistance. The expression of the adeB gene was significantly increased in carbapenem-non-susceptible A. baumannii isolates. In addition, the expression of the adeG gene was 2.08 times higher in isolates capable of forming moderate to strong biofilms compared to those forming weak biofilms. The novelty of this study is a new insight into the relationship between efflux pump expression, antibiotic resistance and biofilm formation in A. baumannii, as well as AdeABC overexpression in carbapenem-resistant isolates and AdeFGH overexpression in biofilm-forming strains, providing potential therapeutic targets. These findings suggest that targeting RND efflux pumps may be a promising strategy to control survival and antibiotic resistance of A. baumannii isolates through biofilm inhibition.
本研究调查了鲍曼不动杆菌分离株中耐药-固氮-细胞分裂（RND）外排泵的基因表达模式，重点关注其与碳青霉烯类耐药性及生物膜形成能力的关联。使用自动肉汤微量稀释技术对102株鲍曼不动杆菌分离株进行了抗生素敏感性测试评估。采用标准化方案评估这些分离株形成生物膜的能力。使用多位点可变数目串联重复分析-8（MLVA-8）方法对分离株进行基因分型，并通过实时PCR定量RND外排泵基因的表达水平。结果显示广泛存在抗生素耐药性，85%的分离株被归类为多重耐药。基因分型结果确定了32种不同的MLVA类型，分为六个簇（A-F）和17种独特基因型。大多数分离株表现出形成生物膜的能力，并且观察到生物膜形成与碳青霉烯类耐药性之间呈负相关。在对碳青霉烯类不敏感的鲍曼不动杆菌分离株中，adeB基因的表达显著增加。此外，与形成弱生物膜的分离株相比，能够形成中度至强生物膜的分离株中adeG基因的表达高2.08倍。本研究的新颖之处在于对鲍曼不动杆菌中外排泵表达、抗生素耐药性和生物膜形成之间的关系有了新的认识，以及碳青霉烯类耐药分离株中AdeABC的过表达和生物膜形成菌株中AdeFGH的过表达，提供了潜在的治疗靶点。这些发现表明，靶向RND外排泵可能是一种有前景的策略，通过抑制生物膜来控制鲍曼不动杆菌分离株的存活和抗生素耐药性。
