A Mouse Model of Acinetobacter baumannii-Associated Pneumonia Using a Clinically Isolated Hypervirulent Strain

Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia us-ing a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infec-tion and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, sig-nificant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100 % of C57BL/6 and BALB/c mice succumbed to 108 CFU of LAC-4 inoculation within 48 h.When this model was used to assess the effi-cacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clini-cal signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40 % of mice from a lethal (100 100 % lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. bau-mannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans. Acinetobacter baumannii infection has recently emerged as amajor cause of health care-associated (hospital- and commu-nity-acquired) infections worldwide (1). The overall 30-day mor-tality of Acinetobacter infection can be as high as 49%, with the respiratory tract being an important portal of entry (2). Indeed