Acute Infection with a Tobramycin-Induced Small Colony Variant of Staphylococcus aureus Causes Increased Inflammation in the Cystic Fibrosis Rat Lung.
Acute Infection with a Tobramycin-Induced Small Colony Variant of Staphylococcus aureus Causes Increased Inflammation in the Cystic Fibrosis Rat Lung.
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妥布霉素诱导的金黄色葡萄球菌小菌落变种的急性感染会导致囊性纤维化大鼠肺部炎症增加。
DOI：
10.1128/iai.00237-22
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发表时间：
2022
影响因子：
3.1
通讯作者：
Birket,SusanE
中科院分区：
文献类型：
--
作者：
Bollar,GretchenE;Keith,JohnathanD;Oden,AshleyM;Kiedrowski,MeganR;Birket,SusanE
囊性纤维化（CF）疾病的特点是终身感染金黄色葡萄球菌等病原体，最终导致呼吸衰竭。金黄色葡萄球菌的小菌落变异 (SCV) 与 CF 患者较差的临床结果有关。目前对 SCV 体内病理学的研究有限，目前尚不清楚 SCV 是否直接影响患者的预后，还是晚期 CF 疾病的结果。为了研究这一点，我们通过用妥布霉素连续传代金黄色葡萄球菌的 CF 分离株，产生了稳定的甲萘醌营养缺陷型 SCV 菌株。妥布霉素是一种氨基糖苷类抗生素，通常用于同时感染铜绿假单胞菌。该 SCV 对妥布霉素具有耐药性，并且对抗葡萄球菌联合疗法磺胺甲恶唑-甲氧苄啶显示出更高的耐受性。为了更好地了解 SCV 体内感染的动态，我们用该菌株感染 CF 大鼠，并与其正常菌落变体 (NCV) 进行比较。感染后 3 天的细菌负荷分析表明，NCV 和 SCV 在肺部同样持续存在，但 SCV 感染最终导致体重减轻和中性粒细胞炎症增加。此外，细胞和组织病理学分析表明，在 CF 大鼠中，SCV 感染产生较低的巨噬细胞反应。总体而言，这些发现表明 SCV 感染可能直接导致 CF 患者肺部疾病的进展。
Cystic fibrosis (CF) disease is characterized by lifelong infections with pathogens such as Staphylococcus aureus, leading to eventual respiratory failure. Small colony variants (SCVs) of S. aureus have been linked to worse clinical outcomes for people with CF. Current studies of SCV pathology in vivo are limited, and it remains unclear whether SCVs directly impact patient outcomes or are a result of late-stage CF disease. To investigate this, we generated a stable menadione-auxotrophic SCV strain by serially passaging a CF isolate of S. aureus with tobramycin, an aminoglycoside antibiotic commonly administered for coinfecting Pseudomonas aeruginosa. This SCV was tobramycin resistant and showed increased tolerance to the anti-staphylococcal combination therapy sulfamethoxazole-trimethoprim. To better understand the dynamics of SCV infections in vivo, we infected CF rats with this strain compared with its normal colony variant (NCV). Analysis of bacterial burden at 3 days postinfection indicated that NCVs and SCVs persisted equally well in the lungs, but SCV infections ultimately led to increased weight loss and neutrophilic inflammation. Additionally, cellular and histopathological analyses showed that in CF rats, SCV infections yielded a lower macrophage response. Overall, these findings indicate that SCV infections may directly contribute to lung disease progression in people with CF.