Adaptation to Potassium-Limitation Is Essential for Acinetobacter baumannii Pneumonia Pathogenesis

Background. Acinetobacter baumannii is challenging the healthcare community as the cause of a wide range of untreatable infections. New targets need to be explored for the development of therapeutics. Methods. The potassium-dependent protein (Kdp) system was investigated via bioinformatics and genet...

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Bibliographic Details
Published in:The Journal of infectious diseases 2016-12, Vol.214 (12), p.2006-2013
Main Authors: Samir, Reham, Hussein, Salma H., Elhosseiny, Noha M., Khattab, Marwa S., Shawky, Alaa E., Attia, Ahmed S.
Format: Article
Language:English
Subjects:
Acinetobacter baumannii - isolation & purification
Acinetobacter baumannii - metabolism
Acinetobacter baumannii - physiology
Acinetobacter Infections - microbiology
Adaptation, Physiological
Animals
BACTERIA
Bacterial Proteins - genetics
Disease Models, Animal
Gene Deletion
Genetic Complementation Test
Male
Mice, Inbred C57BL
Pneumonia, Bacterial - microbiology
Potassium - metabolism
Transcription Factors - genetics
Virulence
Virulence Factors - genetics
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Summary:Background. Acinetobacter baumannii is challenging the healthcare community as the cause of a wide range of untreatable infections. New targets need to be explored for the development of therapeutics. Methods. The potassium-dependent protein (Kdp) system was investigated via bioinformatics and genetic tools. An isogenic mutant was constructed in kdpE and complemented in trans. Gene expression and the ability to grow under potassium-limited conditions were investigated. Finally, the role of KdpE in virulence was examined in the murine pneumonia model. Results. The A. baumannii Kdp system has a distinct arrangement and is well conserved among A. baumannii strains. The genes encoding the 5 members of the system are transcriptionally linked. kdpE is upregulated >70-fold under potassium-limited conditions. The ΔkdpE mutant showed a significant growth defect under potassium-limited conditions and in the colonization of mice lungs. These defects could be restored upon introducing kdpE on a multiple-copy plasmid. Proteomic analyses indicated that KdpE could be regulating several proteins with potential involvement in pathogenesis. Conclusions. For the first time, A. baumannii KdpE is shown to be crucial to pneumonia onset, and targeting this system can be a viable approach to treating these fatal infections.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiw476