An uncharacterized FMAG_01619 protein from Fusobacterium mortiferum ATCC 9817 demonstrates that some bacterial macrodomains can also act as poly-ADP-ribosylhydrolases

Abstract

Macrodomains constitute a conserved fold widely distributed that is not only able to bind ADP-ribose in its free and protein-linked forms but also can catalyse the hydrolysis of the latter. They are involved in the regulation of important cellular processes, such as signalling, differentiation, proliferation and apoptosis, and in host-virus response, and for this, they are considered as promising therapeutic targets to slow tumour progression and viral pathogenesis. Although extensive work has been carried out with them, including their classification into six distinct phylogenetically clades, little is known on bacterial macrodomains, especially if these latter are able to remove poly(ADP-ribose) polymer (PAR) from PARylated proteins, activity that only has been confirmed in human TARG1 (C6orf130) protein. To extend this limited knowledge, we demonstrate, after a comprehensive bioinformatic and phylogenetic analysis, that Fusobacterium mortiferum ATCC 9817 TARG1 (FmTARG1) is the first bacterial macrodomain shown to have high catalytic efficiency towards O-acyl-ADP-ribose, even more than hTARG1, and towards mono- and poly(ADPribosyl)ated proteins. Surprisingly, FmTARG1 gene is also inserted into a unique operonic context, only shared by the distantly related Fusobacterium perfoetens ATCC 29250 macrodomain, which include an immunity protein 51 domain, typical of bacterial polymorphic toxin systems.

Effects of Short-Chain Fatty Acid Modulation on Potentially Diarrhea-Causing Pathogens in Yaks Through Metagenomic Sequencing

“…The infection of T. orientalis may be the main reason for bloody diarrhea in yaks ( Supplementary Figure S1 ). Fusobacterium mortiferum was usually isolated from Crohn’s and Behcet’s patients ( Garcia-Saura et al., 2019 ). Also, Ruminococcus gnavus is a Crohn’s disease-associated pathobiont ( Yu et al., 2020 ), which was in line with the diarrhea symptoms in yaks.…”

Effects of Short Chain Fatty Acids (SCFAs) Modulation on Potentially Diarrhea Causing Pathogens in Yaks Through Metagenomics Sequencing

“…1). Fusobacterium mortiferum was usually isolated from Crohn's and Behcet's disease patients [47], also Ruminococcus gnavus is a Crohn's disease-associated pathobiont [48], which was in line with the diarrhea symptom in yaks. Anaplasma phagocytophilum is a commonly reported emerging tick-borne zoonotic pathogen causing anaplasmosis [49].…”

Expanding the Substrate Specificity of Macro Domains toward 3″-Isomer of O-Acetyl-ADP-ribose

“…Moreover, the F152A mutant was deficient in de-mono-ADP-ribosylation (Figure D,E). These observations implied its role in stabilizing O AADPR distal ribose similar to MacroD-like macro domains regardless of the different phylogenetic origins. , …”

“…The six-clade tree of macro domain proteins has been phylogenetically determined as previously described. , In S. cerevisiae , there are only two macro domains, named Poa1p (YBR022W) and Ymx7 (YML087W), distributed over two branches: ALC1-type and Macro2-type, respectively. In the ALC1-type clade, the Poa1p macro domain belongs to the unique POA1-like subclass, which is mostly restricted to pathogenic fungi and yeasts (Figure S1).…”