Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Buenos Aires, Argentina.
J Med Microbiol. 2021 Jan;70(1). doi: 10.1099/jmm.0.001281. Epub 2020 Nov 27.
has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Sequential isolates of from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. The antibiotic resistance of 11 S. isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC-RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Seven isolates were resistant to trimethoprim-sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC-RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified and genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. The present study shows the long-time persistence of two related clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.
已成为从囊性纤维化 (CF) 患者中分离出的最常见的多药耐药病原体之一。然而,其随时间适应 CF 肺部的情况尚未完全确定。来自巴西成年患者的连续分离株具有克隆相关性,并表现出通过丧失毒力因子而适应的模式。为了研究抗菌药物敏感性、克隆相关性、突变频率、群体感应 (QS) 和选择的毒力因子在 2014 年 5 月至 2018 年 5 月期间,来自阿根廷布宜诺斯艾利斯 CF 转诊中心的巴西成年患者的连续分离株中,11 株 S. aureus 分离株的抗生素耐药性。从一名患有 CF 的成年女性的痰液中回收的 11 株 S. aureus 分离株的抗生素耐药性。在 8 株有活力的分离株中研究了克隆相关性、突变频率、QS 变体 (RpfC-RpfF)、QS 自动诱导物 (DSF) 和毒力因子。7 株 分离株对甲氧苄啶-磺胺甲恶唑耐药,5 株对左氧氟沙星耐药。所有分离株均对米诺环素敏感。检测到强、弱和正常突变体,且随时间推移突变率呈下降趋势。PFGE 显示 7 株分离株属于两个相关克隆。所有分离株均为 RpfC-RpfF1 变体和 DSF 产生菌。只有两个分离株产生弱生物膜,但均无游泳或蠕动运动。4 株分离株表现出蛋白酶活性,并扩增了 基因和 基因。只有前三株分离株是铁载体产生菌。4 株分离株对氧化应激具有高抗性,而最后 4 株分离株对氧化应激具有中度抗性。本研究显示,在一名成年女性 CF 患者中,两个相关的 克隆长期存在。在随时间推移,流行克隆适应 CF 肺部的过程中,我们发现毒力因子逐渐丧失,这可能与进化分离株产生的大量 DSF 有关。此外,在晚期分离株中观察到突变率降低。随着时间的推移,所有这些适应的作用仍有待从临床角度阐明,可能侧重于它们对 CF 肺部造成的损害。