title: Pathogenicity of ocular isolates of Acinetobacter baumannii in a mouse model of bacterial endophthalmitis.
abstract: OBJECTIVE
  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-α, IL-1β, 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.
authors.affiliation: Kresge Eye Institute, Wayne State University, Detroit, Michigan, United States.
authors.forename: Deepa
authors.initials: D
authors.lastname: Talreja
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.forename: Fu-shin
authors.initials: FS
authors.lastname: Yu
authors.forename: Satish K
authors.initials: SK
authors.lastname: Walia
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000151:Acinetobacter Infections / Q000175:diagnosis / Q000382:microbiology* / Q000503:physiopathology; D040981:Acinetobacter baumannii / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004596:Electroretinography; D009877:Endophthalmitis / Q000175:diagnosis / Q000382:microbiology* / Q000503:physiopathology; D015818:Eye Infections, Bacterial / Q000175:diagnosis / Q000382:microbiology* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D012329:RNA, Bacterial / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D012329:RNA, Bacterial
keywords: bacteria; cell death; endophthalmitis; inflammation; innate response