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Nat Microbiol. 2018 May;3(5):563-569. doi: 10.1038/s41564-018-0151-5. Epub 2018 Apr 23.

A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii.

Chin CY1,2,3,4, Tipton KA5, Farokhyfar M6, Burd EM3,4,7, Weiss DS8,9,10,11,12, Rather PN13,14,15.

Author information

1
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
2
Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA, USA.
3
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
4
Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA, USA.
5
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
6
Research Service, Atlanta VA Medical Center, Decatur, GA, USA.
7
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
8
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. david.weiss@emory.edu.
9
Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA, USA. david.weiss@emory.edu.
10
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. david.weiss@emory.edu.
11
Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA, USA. david.weiss@emory.edu.
12
Research Service, Atlanta VA Medical Center, Decatur, GA, USA. david.weiss@emory.edu.
13
Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA, USA. prather@emory.edu.
14
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA. prather@emory.edu.
15
Research Service, Atlanta VA Medical Center, Decatur, GA, USA. prather@emory.edu.

Abstract

Antibiotic-resistant infections lead to 700,000 deaths per year worldwide 1 . The roles of phenotypically diverse subpopulations of clonal bacteria in the progression of diseases are unclear. We found that the increasingly pathogenic and antibiotic-resistant pathogen Acinetobacter baumannii harbours a highly virulent subpopulation of cells responsible for disease. This virulent subpopulation possesses a thicker capsule and is resistant to host antimicrobials, which drive its enrichment during infection. Importantly, bacteria harvested from the bloodstream of human patients belong exclusively to this virulent subpopulation. Furthermore, the virulent form exhibits increased resistance to hospital disinfectants and desiccation, indicating a role in environmental persistence and the epidemic spread of disease. We identified a transcriptional 'master regulator' of the switch between avirulent and virulent cells, the overexpression of which abrogates virulence. Furthermore, the overexpression strain is capable of vaccinating mice against lethal challenge. This work highlights a phenotypic subpopulation of bacteria that drastically alters the outcome of infection, and illustrates how knowledge of the regulatory mechanisms controlling such phenotypic switches can be harnessed to attenuate bacteria and develop translational interventions.

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