Identification of osmo‐dependent and osmo‐independent betaine‐choline‐carnitine transporters in Acinetobacter baumannii: role in osmostress protection and metabolic adaptation

Abstract

Acinetobacter baumannii is outstanding for its ability to cope with low water activities and therefore its adaptation mechanism to osmotic stress. Here we report on the identification and characterization of five different secondary active compatible solute transporters, belonging to the betaine-choline-carnitine transporter (BCCT) family. Our studies revealed two choline-specific and three glycine betaine-specific BCCTs. Activity of the BCCTs was differentially dependent to the osmolality: one choline and one betaine transporter were osmostress-independent. Addition of choline to resting cells of Acinetobacter grown in the presence of the co-substrate choline or with phosphatidylcholine as sole carbon source led to ATP synthesis in the wild type but not in the BCCT quadruple mutant. This indicates that the BCCTs are essential to transport the energy substrate choline. The role of the different BCCTs in osmostress resistance and in metabolic adaptation of A. baumannii to the human host is discussed.

CsrA Coordinates Compatible Solute Synthesis in Acinetobacter baumannii and Facilitates Growth in Human Urine

“…The response to hyperosmotic stress, as encountered in urine, has been studied in A. baumannii in recent years ( 16 , 31 – 41 ). A. baumannii accumulates so-called compatible solutes ( 36 , 39 ). An increase in the cytoplasmic solute content causes a decrease of the concentration gradient between the intra- and the extracellular medium; thereby, the loss of cellular water is reduced, and cell-shrinking and death are prevented ( 42 ).…”

“…An increase in the cytoplasmic solute content causes a decrease of the concentration gradient between the intra- and the extracellular medium; thereby, the loss of cellular water is reduced, and cell-shrinking and death are prevented ( 42 ). In the presence of the compatible solute glycine betaine—or its precursor choline—solutes are taken up by the action of different betaine-choline-carnitine transporters (BCCTs) ( 39 ). In the absence of compatible solutes in the medium, A. baumannii synthesizes the compatible solutes glutamate, mannitol, and trehalose de novo ( 36 ).…”

The choline dehydrogenase BetA of Acinetobacter baumannii: a flavoprotein responsible for osmotic stress protection

“…The corresponding genes are organized in an operon and are under the regulation of a TetR-type transcriptional regulator (BetI) (Scholz et al, 2016). A betIBA operon was also found in A. baumannii, located upstream of the two transporter genes (betT1 and betT2), which are essential for osmostress-dependent and -independent choline uptake (Breisch and Averhoff, 2020).…”

“…The opportunistic human pathogen Acinetobacter baumannii is known for its outstanding resistance to low water activities (Jawad et al ., 1996; Wendt et al ., 1997; Zeidler et al ., 2017; Breisch et al ., 2018; Zeidler et al ., 2018; Zeidler and Müller, 2018; Zeidler and Müller, 2019; Breisch and Averhoff, 2020). It synthesizes glutamate and mannitol as the main compatible solutes but also trehalose in minor amounts (Zeidler et al ., 2017; Zeidler et al ., 2018).…”

“…A betIBA operon was also found in A . baumannii , located upstream of the two transporter genes ( betT1 and betT2 ), which are essential for osmostress‐dependent and ‐independent choline uptake (Breisch and Averhoff, 2020).…”