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

Abstract

ABSTRACTAcinetobacter baumanniiis an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models ofA. baumanniipneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model ofA. baumanniipneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonaryA. baumanniiinfection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant 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 108CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical 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 ofA. baumanniipneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines againstA. baumanniipneumonia in humans.