Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Microb Genom. 2021 Mar;7(3). doi: 10.1099/mgen.0.000510. Epub 2021 Feb 18.
chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant (MRSA) infections in Argentina - ST5 and ST30 - are also frequently isolated from the sputum of patients with CF, but in these patients they usually display multi-drug antimicrobial resistance. In this study, we sequenced the genomes of MRSA from four paediatric CF patients with the goal of identifying mutations among sequential isolates, especially those possibly related to antimicrobial resistance and virulence, which might contribute to the adaptation of the pathogen in the airways of patients with CF. Our results revealed genetic differences in sequential MRSA strains isolated from patients with CF in both their core and accessory genomes. Although the genetic adaptation of was distinct in different hosts, we detected independent mutations in and - which are known to have crucial roles in virulence and antimicrobial resistance - in isolates recovered from multiple patients. Moreover, we identified allelic variants that were detected in all of the isolates recovered after a certain time point; these non-synonymous mutations were in genes associated with antimicrobial resistance, virulence, iron scavenging and oxidative stress resistance. In conclusion, our results provide evidence of genetic variability among sequential MRSA isolates that could be implicated in the adaptation of these strains during chronic CF airway infection.
囊性纤维化（CF）患者的慢性气道感染使这种病原体能够随着时间的推移适应不同的选择压力。我们之前曾表明，与阿根廷社区获得性耐甲氧西林金黄色葡萄球菌（MRSA）感染相关的主要序列类型 - ST5 和 ST30 - 也经常从 CF 患者的痰中分离出来，但在这些患者中，它们通常表现出多药抗微生物药物耐药性。在这项研究中，我们对来自四名儿科 CF 患者的 MRSA 基因组进行了测序，目的是鉴定连续分离株中的突变，特别是那些可能与抗微生物药物耐药性和毒力相关的突变，这些突变可能有助于病原体在 CF 患者的气道中适应。我们的研究结果揭示了从 CF 患者中分离出的连续 MRSA 菌株在其核心和辅助基因组中存在遗传差异。尽管在不同的宿主中，的遗传适应是不同的，但我们在从多个患者中回收的分离株中检测到了 和 中的独立突变，这两个基因已知在毒力和抗微生物药物耐药性中发挥着关键作用。此外，我们还鉴定了在某个时间点之后回收的所有分离株中都检测到的等位基因变异体；这些非同义突变与抗微生物药物耐药性、毒力、铁摄取和氧化应激抗性相关的基因有关。总之，我们的研究结果提供了证据，表明连续的 MRSA 分离株之间存在遗传变异性，这可能与这些菌株在慢性 CF 气道感染期间的适应性有关。
