title: Adaptation to Potassium-Limitation Is Essential for Acinetobacter baumannii Pneumonia Pathogenesis.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy.
authors.forename: Reham
authors.initials: R
authors.lastname: Samir
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy.
authors.forename: Salma H
authors.initials: SH
authors.lastname: Hussein
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy.
authors.forename: Noha M
authors.initials: NM
authors.lastname: Elhosseiny
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
authors.forename: Marwa S
authors.initials: MS
authors.lastname: Khattab
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy.
authors.forename: Alaa E
authors.initials: AE
authors.lastname: Shawky
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008297:Male; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D011188:Potassium / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D037521:Virulence Factors; D011188:Potassium
keywords: A. baumannii; KdpE; drug targets; pathogenesis; pneumonia; potassium; virulence