Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii
| Autor: | Louis de Léséleuc, Rhonda KuoLee, H. Howard Xu, Wangxue Chen, Greg Harris |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Acinetobacter baumannii
Serum Microbiology (medical) Blood Bactericidal Activity Virulence Bacteremia Gallium Heme Biology Microbiology chemistry.chemical_compound Drug Resistance Bacterial Pneumonia Bacterial medicine Animals Humans chemistry.chemical_classification Gallium nitrate Lactoferrin General Medicine biology.organism_classification Mice Inbred C57BL Heme oxygenase Disease Models Animal Infectious Diseases chemistry Transferrin biology.protein Cattle Female Fetal bovine serum Acinetobacter Infections medicine.drug |
| Zdroj: | International Journal of Medical Microbiology. 304:360-369 |
| ISSN: | 1438-4221 |
| Popis: | Bacteremia caused by Acinetobacter baumannii is a highly lethal complication of hospital-acquired pneumonia. In the present study, we investigated the serum resistance, gallium nitrate tolerance and heme consumption of A. baumannii strain LAC-4 which was recently reported to display high virulence in a mouse pneumonia model with extrapulmonary dissemination leading to fatal bacteremia. This strain showed enhanced growth in mouse and fetal bovine serum that was independent of complement and was not observed with regular growth media. The LAC-4 strain was found to possess a high tolerance to gallium nitrate (GaN), whereas serum synergized with GaN in inhibiting A. baumannii strain ATCC 17978. We found that LAC-4 contains a heme oxygenase gene and expresses a highly efficient heme consumption system. This system can be fully blocked in vitro and in vivo by gallium protoporphyrin IX (GaPPIX). Inhibition of heme consumption by GaPPIX completely abrogated the growth advantage of LAC-4 in serum as well as its tolerance to GaN. More importantly, GaPPIX treatment of mice intranasally infected with LAC-4 prevented extrapulmonary dissemination and death. Thus, we propose that heme provides an additional source of iron for LAC-4 to bypass iron restriction caused by serum transferrin, lactoferrin or free gallium salts. Heme consumption systems in A. baumannii may constitute major virulence factors for lethal bacteremic isolates. © 2014. |
| Databáze: | OpenAIRE |
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