Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
Department of Biomolecular Science sect. Biotechnology, University of Urbino "Carlo Bo", Urbino, Italy.
Adv Exp Med Biol. 2021;1323:71-80. doi: 10.1007/5584_2020_570.
Extensively-drug-resistant Pseudomonas aeruginosa constitutes a serious threat to patients suffering from Cystic Fibrosis (CF). In these patients, P. aeruginosa lung infection is commonly treated with aminoglycosides, but treatments are largely unsuccessful due a variety of resistance mechanisms. Here we investigate the prevalence of resistance to gentamicin, amikacin and tobramycin and the main aminoglycoside resistance genes found in P. aeruginosa strains isolated at a regional CF centre.
A total number of 147 randomly selected P. aeruginosa strains isolated from respiratory samples sent by the Marche regional Cystic Fibrosis Centre to the Microbiology lab, were included in this study. Of these, 78 (53%) were resistant to at least one of the three aminoglycosides tested and 27% were resistant to all three antibiotics, suggesting a major involvement of a chromosome-encoded mechanism, likely MexXY-OprM efflux pump overexpression. A specific pathogenic clone (found in 7/78 of the aminoglycoside resistant strains) carrying ant(2″)-Ia was isolated over time from the same patient, suggesting a role for this additional resistance gene in the antibiotic unresponsiveness of CF patients.
The MexXY-OprM efflux pump is confirmed as the resistance determinant involved most frequently in P. aeruginosa aminoglycoside resistance of CF lung infections, followed by the ant(2″)-Ia-encoded adenylyltransferase. The latter may prove to be a novel target for new antimicrobial combinations against P. aeruginosa.
广泛耐药的铜绿假单胞菌对患有囊性纤维化 (CF) 的患者构成严重威胁。在这些患者中,铜绿假单胞菌肺部感染通常用氨基糖苷类药物治疗,但由于多种耐药机制,治疗效果大多不理想。在这里,我们调查了在区域 CF 中心分离的铜绿假单胞菌菌株对庆大霉素、阿米卡星和妥布霉素的耐药率以及主要氨基糖苷类耐药基因的流行情况。
本研究共纳入了从马尔凯地区囊性纤维化中心呼吸样本中随机选择的 147 株铜绿假单胞菌。其中,78 株(53%)对至少一种三种氨基糖苷类药物中的一种耐药,27%对三种抗生素均耐药,这表明可能涉及染色体编码机制,可能是 MexXY-OprM 外排泵过度表达。随着时间的推移,从同一患者中分离出一种特定的致病性克隆(在 78 株氨基糖苷类耐药株中的 7 株中发现),携带 ant(2″)-Ia,表明该额外的耐药基因在 CF 患者对抗生素无反应中起作用。
MexXY-OprM 外排泵被确认为 CF 肺部感染中铜绿假单胞菌氨基糖苷类耐药最常涉及的耐药决定因素,其次是编码腺苷酰转移酶的 ant(2″)-Ia。后者可能成为针对铜绿假单胞菌的新型抗菌组合的新靶标。