Pathogenicity of Ocular Isolates of Acinetobacter baumannii in a Mouse Model of Bacterial Endophthalmitis

摘要

Purpose.: To determine the virulence properties of ocular isolates of Acinetobacter baumannii in causing endophthalmitis in a mouse model. Methods.: Endophthalmitis was induced by intravitreal injections of the bacteria into C57BL/6 (B6) mouse eyes. The disease progression was monitored by ophthalmoscopic, electroretinography (ERG), histologic, cell death (TUNEL labeling), and microbiological parameters. The expression of cytokines/chemokines was checked by quantitative RT-PCR (qRT-PCR) and ELISA. Flow cytometry was used to determine cellular infiltration. The role of neutrophils was determined using neutropenic mice. The virulence traits (biofilm formation, adherence, and cytotoxicity) of the ocular isolates were tested using corneal epithelial cells. Results.: Among the three clinical isolates and a standard ATCC 19606 strain tested, a biofilm producing multidrug resistant (MDR) strain of A. baumannii AB12 caused severe endophthalmitis (100% destruction of the eyes) leading to the loss of retinal function as assessed by ERG analysis. Elevated levels of inflammatory mediators (TNF-?±, IL-1?2, CXCL2, and IL-6) were detected in AB12-infected eyes. Histologic and TUNEL staining revealed increased retinal cell death and the flow cytometry data showed the presence of inflammatory cells, primarily neutrophils (CD45+/Ly6G+). Neutropenic mice showed an increased bacterial burden, reduced inflammatory response, and severe tissue destruction. Conclusions.: These results indicate that A. baumannii causes severe intraocular inflammation and retinal damage. Furthermore, neutrophils play an important role in the pathogenesis of A. baumannii endophthalmitis.