Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.
Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.
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DOI：
10.3390/antibiotics10091033
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发表时间：
2021-08-25
期刊：
影响因子：
--
通讯作者：
Shanks RMQ
中科院分区：
文献类型：
--
作者：
Harshaw NS;Stella NA;Lehner KM;Romanowski EG;Kowalski RP;Shanks RMQ
Rcs磷酸化继电器是细菌应激反应系统，其响应于包膜应激，并进而控制许多细菌物种的几种毒力相关途径，包括荚膜、鞭毛和毒素生物合成。Rcs系统还影响抗生素耐受性、生物膜形成和水平基因转移。最近证明眼部细菌病原体粘质沙雷氏菌的Rcs系统影响角膜炎兔模型中的眼部发病机制，Rcs缺陷突变体引起更大的病理学，Rcs激活的菌株表现出减少的炎症。Rcs系统可被多种刺激激活，包括β-内酰胺抗生素和多粘菌素B。在这项研究中，我们开发了三种基于发光的Rcs系统活性的转录报告基因，并使用它们来测试用于经验性治疗眼部感染的抗生素是否会影响角膜炎分离株S. marcescens。这些包括细菌敏感和耐药的抗生素。结果表明，头孢唑林，头孢他啶，多粘菌素B，万古霉素激活Rcs系统不同程度的RcsB依赖的方式，而环丙沙星和妥布霉素激活启动子融合，但在一个Rcs独立的方式。尽管最小抑菌浓度（MIC）分析表明试验细菌对多粘菌素B和万古霉素具有耐药性，但这些抗生素的亚抑菌浓度可激活Rcs系统。总之，这些数据表明，影响许多致病表型和耐药性的细菌应激系统受到不同类别抗生素的影响，尽管细菌的易感性状态。
The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen Serratia marcescens was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation. The Rcs system is activated by a variety of insults, including β-lactam antibiotics and polymyxin B. In this study, we developed three luminescence-based transcriptional reporters for Rcs system activity and used them to test whether antibiotics used for empiric treatment of ocular infections influence Rcs system activity in a keratitis isolate of S. marcescens. These included antibiotics to which the bacteria were susceptible and resistant. Results indicate that cefazolin, ceftazidime, polymyxin B, and vancomycin activate the Rcs system to varying degrees in an RcsB-dependent manner, whereas ciprofloxacin and tobramycin activated the promoter fusions, but in an Rcs-independent manner. Although minimum inhibitory concentration (MIC) analysis demonstrated resistance of the test bacteria to polymyxin B and vancomycin, the Rcs system was activated by sub-inhibitory concentrations of these antibiotics. Together, these data indicate that a bacterial stress system that influences numerous pathogenic phenotypes and drug-tolerance is influenced by different classes of antibiotics despite the susceptibility status of the bacterium.
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影响因子：
3.4
作者：
Kowalski RP;Romanowski EG;Mah FS;Shanks RM;Gordon YJ
通讯作者：
Gordon YJ
影响因子：
3.2
作者：
Bruna, Roberto E.;Victoria Molino, Maria;Garcia Vescovi, Eleonora
通讯作者：
Garcia Vescovi, Eleonora
影响因子：
3.1
作者：
Di Venanzio, Gisela;Stepanenko, Tatiana M.;Garcia Vescovi, Eleonora
通讯作者：
Garcia Vescovi, Eleonora
影响因子：
3.2
作者：
Farris, Carol;Sanowar, Sarah;Miller, Samuel I.
通讯作者：
Miller, Samuel I.
影响因子：
2.8
作者：
Healy, DP;Holland, EJ;Davis, E
通讯作者：
Davis, E