The carnitine degradation pathway of Acinetobacter baumannii and its role in virulence

  • The opportunistic human pathogen Acinetobacter baumannii can grow with carnitine but its metabolism, regulation and role in virulence remained elusive. Recently, we identified a carnitine transporter encoded by a gene closely associated with potential carnitine degradation genes. Among those is a gene coding for a putative d-malate dehydrogenase (Mdh). Deletion of the mdh gene led to a loss of growth with carnitine but not l-malate; growth with d-malate was strongly reduced. Therefore, it is hypothesized that d-malate is formed during carnitine oxidation and further oxidized to CO2 and pyruvate and, that not, as previously suggested, l-malate is the product and funnelled directly into the TCA cycle. Mutant analyses revealed that the hydrolase in this cluster funnels acetylcarnitine into the degradation pathway by deacetylation. A transcriptional regulator CarR bound in a concentration-dependent manner to the intergenic region between the mdh gene, the first gene of the carnitine catabolic operon and the carR gene in the presence and absence of carnitine. Both carnitine and d-malate induced CarR-dependent expression of the carnitine operon. Infection studies with Galleria mellonella larvae demonstrated a strong increase in virulence by addition of carnitine indicating that carnitine degradation plays a pivotal role in virulence of A. baumannii.
Author:Jennifer Maria BreischGND, Clemens Schumm, Anja PoehleinORCiDGND, Rolf DanielORCiDGND, Beate AverhoffORCiD
Parent Title (English):Environmental microbiology
Place of publication:Oxford [u.a.]
Document Type:Article
Date of Publication (online):2022/06/02
Date of first Publication:2022/06/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/10/23
Page Number:12
First Page:4437
Last Page:4448
This study was supported by a grant from the Deutsche Forschungsgemeinschaft through DFG Research Unit FOR2251.
Transcriptome data have been deposited in the National Center for Biotechnology Information’s (NCBI) Sequence Read Archive (SRA) as BioProject PRJNA821016. All other data of this study are available from the corresponding author upon reasonable request.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International