Project Details
Projekt
Metabolic adaptation of Acinetobacter baumannii - role of phospholipids in nutrition and infection
Applicant
Professorin Dr. Beate Averhoff
Subject Area
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 258351992
Membranous environments are colonized by various strains of A. baumannii, which raises the question on how A. baumannii manages to adapt its metabolism to the host environment. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids found in human cell membranes and make them good candidates as carbon and energy source. The degradation of phosphoglycerolipids is facilitated by a set of different phospholipases. Phospholipases also modulate the phospholipid composition of bacterial membranes, which is crucial to survive the immune defence system of eukaryotic host cells. Therefore, phospholipases play a key role in pathobiology. In our preceding studies we have identified three phospholipases D (PLDs) and two phospholipases C (PLCs) in A. baumannii acting in concerted manner in invasion of G. mellonella caterpillars and lung epithelial cells. Next, we will purify and biochemically characterize the PLDs to unravel their mode of action. Moreover, we will address the subcellular localization and regulation of the PLDs. We identified multiple osmo-independent BCC transporter for choline and glycine betaine which suggests an additional role of the BCCTs other than osmostress protection. One could be a role of choline as energy source as we have found in A. baylyi. We will address the role of choline and glycine betaine uptake in host adaptation by mutant studies in G. mellonella and in lung epithelial cell cultures. The role of choline and glycine betaine as potential carbon or nitrogen source will also be analyzed. Moreover, a role of choline and glycine betaine as regulatory metabolites triggering the "sensing" of choline rich host environments thereby leading to transcriptional modulation of virulence factors will be addressed. We have also identified a broad variety of cardiolipins (CL) and monolysocardiolipins (MLCL) in A. baumannii. The latter has been very rarely detected in bacteria. CLs are known to play important roles in virulence of pathogenic bacteria whereas the function of MLCLs is unclear. We found that PLD2 and PLD3 are both essential for CL and MLCL production. Next, we will investigate the PLD2- and PLD3-mediated synthesis of CL and MLCL. Moreover, we aim to elucidate the distribution of CL and MLCL in both membranes of A. baumannii. Membrane lipid composition of bacteria changes in response to environmental changes. We will analyze the effect of host infection on pld expression and PLD production. Moreover, the effect of PLD2 and PLD3 overproduction on virulence will be addressed. Our working hypothesis is that the large variety of CLs and MLCLs plays a role of lipid A modulation thereby contributing to adaptation and persistence in the human host. We will analyze the role of CL and MLCL in lipid A modulation by comparison of fatty acids linked to lipid A in A. baumannii pld2/pld3 mutants and in wildtype cells.
DFG Programme
Research Units
