4.4 Article

K+ and its role in virulence of Acinetobacter baumannii

Journal

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.ijmm.2021.151516

Keywords

Pathogen; Osmostress; Virulence; Persistence; Drought

Funding

  1. Deutsche Forschungsgemeinschaft [FOR 2251]

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Acinetobacter baumannii is a global threat to healthcare institutions due to its multiple antibiotic resistances and ability to persist in low water activity environments. Deletion of K+ transporter genes in A. baumannii results in growth defects and metabolic dysfunction, affecting its pathogenicity in the host. The mutants also show reduced resistance to reactive oxygen species and impaired virulence, providing insights into the importance of K+ uptake in pathogenicity.
Acinetobacter baumannii is an opportunistic human pathogen that has become a global threat to healthcare institutions worldwide. The success of A. baumannii is based on the rise of multiple antibiotic resistances and its outstanding potential to persist in the human host and under conditions of low water activity in hospital environments. Combating low water activities involves osmoprotective measures such as uptake of compatible solutes and K+. To address the role of K+ uptake in the physiology of A. baumannii we have identified K+ transporter encoding genes in the genome of A. baumannii ATCC 19606. The corresponding genes (kup, trk, kdp) were deleted and the phenotype of the mutants was studied. The triple mutant was defective in K+ uptake which resulted in a pronounced growth defect at high osmolarities (300 mM NaCl). Additionally, mannitol and glutamate synthesis were strongly reduced in the mutant. To mimic host conditions and to study its role as an uropathogen, we performed growth studies with the K+ transporter deletion mutants in human urine. Both, the double (AkupAtrk) and the triple mutant were significantly impaired in growth. This could be explained by the inability of AkupAtrkAkdp to metabolize various amino acids properly. Moreover, the reactive oxygen species resistance of the triple mutant was significantly reduced in comparison to the wild type, making it susceptible to one essential part of the innate immune response. Finally, the triple and the double mutant were strongly impaired in Galleria mellonella killing giving first insights in the importance of K+ uptake in virulence.

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