Malate-Dependent Carbon Utilization Enhances Central Metabolism and Contributes to Biological Fitness of Laribacter hongkongensis via CRP Regulation

Abstract

Metabolic adaptation in various environmental niches is crucial for bacterial extracellular survival and intracellular replication during infection. However, the metabolism of carbon/nitrogen sources and related regulatory mechanisms in Laribacter hongkongensis , an asaccharolytic bacterium associated with invasive infections and gastroenteritis, are still unknown. In the present study, we demonstrated that malate can be exploited as a preferred carbon source of L. hongkongensis . Using RNA-sequencing, we compared the transcription profiles of L. hongkongensis cultivated with or without malate supplementation, and observed that malate utilization significantly inhibits the use of alternative carbon sources while enhancing respiratory chain as well as central carbon, sulfur, and urease-mediated nitrogen metabolisms. The tight connection among these important metabolic pathways indicates that L. hongkongensis is capable of integrating information from different metabolism branches to coordinate the expression of metabolic genes and thereby adapt to environmental changing. Furthermore, we identified that a transcription factor, CRP, is repressed by malate-mediated metabolism while negatively regulating the effect of malate on these central metabolic pathways. Remarkably, CRP also responds to various environmental stresses, influences the expression of other transcription factors, and contributes to the biological fitness of L. hongkongensis . The regulatory network and cross-regulation enables the bacteria to make the appropriate metabolic responses and environmental adaptation.

Cross-feeding options define eco-evolutionary dynamics of deep oligotrophic groundwater microbiome

“…2OG and OAA interconnect carbon and nitrogen metabolism 22,23 with 2OG being the main precursor for amino acid biosynthesis (glutamate/glutamine) and nitrogen assimilation 23 . Glutamate is generated via either the glutamine synthetase-glutamine oxoglutarate aminotransferase (GS-GOGAT) pathway (P43, P44, and P46) or the glutamate dehydrogenase (GDH) pathway (P45), both of which assimilate ammonium while using 2OG as a carbon backbone 23,24 . The GDH pathway does not require ATP, but the GS-GOGAT pathway does 25 .…”

“…The GDH pathway does not require ATP, but the GS-GOGAT pathway does 25 . However, GS-GOGAT is known to be more efficient under low concentrations of 2OG or ammonium and produces two molecules of glutamate 23,24 . Both ammonium assimilation pathways were prevalent among high GC-content lineages (Supplementary Fig.…”

“…S12). Furthermore, malate as a regulator of the central carbon metabolism 24 , can be compensated for by the glyoxylate cycle as an anaplerotic pathway.…”

Pan-Genome Analysis of Laribacter hongkongensis: Virulence Gene Profiles, Carbohydrate-Active Enzyme Prediction, and Antimicrobial Resistance Characterization

“…The serological detection methods were established ( Tse et al, 2014 ; Wang et al, 2017 ). The adaptive response and transcriptional regulation patterns of L. hongkongensis coupled with different nutritional sources, aerobic or anaerobic conditions, and different temperatures were also studied ( Xiong L. et al, 2015 ; Kong et al, 2016 , 2017 ; Xiong et al, 2017 , 2019 ). Researchers also discussed the pathogenicity factors of L. hongkongensis ( Xie et al, 2014 ).…”