BACKGROUND: Severe Acinetobacter baumannii infections in immunocompetent patients are uncommon, and the virulence mechanisms of this organism are not fully understood. METHODS: Following an outbreak of fatal A. baumannii infections in a cohort of relatively immunocompetent patients (low comorbidity and illness severity scores), isolates were investigated with comparative genomics and in animal models. RESULTS: Two unrelated A. baumannii clades were associated with the outbreak. The clone associated with the majority of patient deaths, clade B, is evolutionarily distinct from the 3 international clonal complexes, belongs to multilocus sequence type (MLST) 10, and is most closely related to strains isolated from the Czech Republic, California, and Germany in 1994, 1997, and 2003, respectively. In 2 different murine models, clade B isolates were more virulent than comparator strains, including the highly virulent reference strain AB5075. The most virulent clade B derivative, MRSN 16897, was isolated from the patient with the lowest combined comorbidity/illness severity score. Clade B isolates possess a unique combination of putative virulence genes involved in iron metabolism, protein secretion, and glycosylation, which was leveraged to develop a rapid and specific clinical assay to detect this clade that cannot be distinguished by MLST. CONCLUSIONS: Clade B warrants continued surveillance and investigation. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Severe Acinetobacter baumannii infections in immunocompetent patients are uncommon, and the virulence mechanisms of this organism are not fully understood. METHODS: Following an outbreak of fatal A. baumannii infections in a cohort of relatively immunocompetent patients (low comorbidity and illness severity scores), isolates were investigated with comparative genomics and in animal models. RESULTS: Two unrelated A. baumannii clades were associated with the outbreak. The clone associated with the majority of patient deaths, clade B, is evolutionarily distinct from the 3 international clonal complexes, belongs to multilocus sequence type (MLST) 10, and is most closely related to strains isolated from the Czech Republic, California, and Germany in 1994, 1997, and 2003, respectively. In 2 different murine models, clade B isolates were more virulent than comparator strains, including the highly virulent reference strain AB5075. The most virulent clade B derivative, MRSN 16897, was isolated from the patient with the lowest combined comorbidity/illness severity score. Clade B isolates possess a unique combination of putative virulence genes involved in iron metabolism, protein secretion, and glycosylation, which was leveraged to develop a rapid and specific clinical assay to detect this clade that cannot be distinguished by MLST. CONCLUSIONS: Clade B warrants continued surveillance and investigation. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Entities:
Keywords:
Acinetobacter baumannii; extensively drug resistant; outbreak; virulence
Authors: Hajime Kanamori; Christian M Parobek; David J Weber; David van Duin; William A Rutala; Bruce A Cairns; Jonathan J Juliano Journal: Antimicrob Agents Chemother Date: 2015-12-07 Impact factor: 5.191
Authors: Kurt H Piepenbrink; Erik Lillehoj; Christian M Harding; Jason W Labonte; Xiaotong Zuo; Chelsea A Rapp; Robert S Munson; Simeon E Goldblum; Mario F Feldman; Jeffrey J Gray; Eric J Sundberg Journal: J Biol Chem Date: 2016-09-15 Impact factor: 5.157
Authors: Darren Wong; Travis B Nielsen; Robert A Bonomo; Paul Pantapalangkoor; Brian Luna; Brad Spellberg Journal: Clin Microbiol Rev Date: 2017-01 Impact factor: 26.132
Authors: Carl Wepking; Bethany Avera; Brian Badgley; John E Barrett; Josh Franklin; Katharine F Knowlton; Partha P Ray; Crystal Smitherman; Michael S Strickland Journal: Proc Biol Sci Date: 2017-03-29 Impact factor: 5.349
Authors: Guillermo D Repizo; Stéphanie Gagné; Marie-Laure Foucault-Grunenwald; Vitor Borges; Xavier Charpentier; Adriana S Limansky; João Paulo Gomes; Alejandro M Viale; Suzana P Salcedo Journal: PLoS One Date: 2015-09-24 Impact factor: 3.240