title: A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain.
abstract: 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 using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection 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 10(8) CFU 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 of A. baumannii 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.
authors.affiliation: Vaccine Program, Human Health Therapeutics, National Research Council Canada, Ottawa, Ontario, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Harris
authors.forename: Rhonda
authors.initials: R
authors.lastname: Kuo Lee
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Lam
authors.forename: Gregory
authors.initials: G
authors.lastname: Kanzaki
authors.forename: Girishchandra B
authors.initials: GB
authors.lastname: Patel
authors.forename: H Howard
authors.initials: HH
authors.lastname: Xu
authors.forename: Wangxue
authors.initials: W
authors.lastname: Chen
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology / Q000517:prevention & control; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000276:immunology / Q000517:prevention & control; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001835:Body Weight / Q000187:drug effects; D001996:Bronchopneumonia / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D015378:Imipenem / Q000494:pharmacology; D007114:Immunization / Q000379:methods; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control*; D015203:Reproducibility of Results; D000078304:Tigecycline; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D000078304:Tigecycline; D015378:Imipenem; D008911:Minocycline