The carnitine degradation pathway ofAcinetobacter baumanniiand its role in virulence

Abstract

Summary 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.

Choline degradation inParacoccus denitrificans: identification of sources of formaldehyde

“…It was therefore unexpected that our mutant lacking both GbcAB and HpbC2B2 (which cannot grow on glycine betaine) retains some ability to grow on carnitine, albeit significantly less well than wild type. One possible explanation is that P. denitrificans has an alternative pathway for carnitine degradation that does not generate glycine betaine, as described in Acinetobacter baumanii (35). Some of the enzymes of this pathway appear to be conserved in P. denitrificans , however there is no indication that this strain can catabolize the trimethylamine by-product of carnitine metabolism by the A. baumanii pathway (10, 35).…”

“…One possible explanation is that P. denitrificans has an alternative pathway for carnitine degradation that does not generate glycine betaine, as described in Acinetobacter baumanii (35). Some of the enzymes of this pathway appear to be conserved in P. denitrificans, however there is no indication that this strain can catabolize the trimethylamine by-product of carnitine metabolism by the A. baumanii pathway (10,35).…”

Identification and characterization of a novel pathway for aldopentose degradation in Acinetobacter baumannii

“…Extraction of RNA and transcriptome analyses was done as described by Breisch, Schumm, et al (2022). Genes with a log 2 ‐fold change (FC) of +2/−2 and a p ‐adjust value <0.05 were considered differentially expressed.…”

Domain-architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogenAcinetobacter baumannii

“…The world-wide spread of multi-or even pan-resistant A. baumannii isolates [4][5][6] is accompanied by a surge in virulence [6][7][8][9][10], and thus novel therapeutic treatments are necessary for a sustainable infection management. Over the past years, experimental studies integrated with comparative genomics analyses have therefore sought to identify genetic determinants of A. baumannii virulence [11][12][13][14][15][16][17][18][19][20][21][22][23]. The identified factors are involved into a broad spectrum of biological processes including NOS and ROS resistance and metabolic adaptation, but some also indicate changes in the way how the pathogen interacts with its environment [17,20].…”