Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain

Abstract

Arr is an ADP-ribosyltransferase enzyme primarily reported in association with rifamycin resistance, which has been used to treat tuberculosis in addition to Gram-positive infections and, recently, pan-resistant Gram-negative bacteria. The arr gene was initially identified on the Mycolicibacterium smegmatis chromosome and later on Proteobacteria plasmids. This scenario raised concerns on the distribution and spread of arr, considering the Bacteria domain. Based on 198,082 bacterial genomes/metagenomes, we performed in silico analysis, including phylogenetic reconstruction of Arr in different genomic contexts. Besides, new arr alleles were evaluated by in vitro analysis to assess their association with rifampin resistance phenotype. The arr gene was prevalent in thousands of chromosomes and in hundreds of plasmids from environmental and clinical bacteria, mainly from the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. Furthermore, this gene was identified in other and new genomic contexts. Interestingly, Arr sequences associated with rifampin resistance were distributed across all phylogeny, indicating that, despite the diversity, their association with rifampin resistance phenotype were maintained. In fact, we found that the key residues were highly conserved. In addition, other analyzes have raised evidence of another Arr function, which is related to guanidine metabolism. Finally, this scenario as a whole also suggested the Actinobacteria phylum as a potential ancestral source of arr within the Bacteria domain.

Whole-genome sequence and resistance determinants of four Elizabethkingia anophelis clinical isolates collected in Hanoi, Vietnam

“…The rifampicin-resistance gene arr , detected in EAV_NVB490, EAV_NNN508 and EAV_NVH72, is a class I ADP-ribosyltransferase that inactivates rifampicin 60 . Arr enzymes are widespread in bacteria and have already been identified in the Bacteroidota phylum 61 . EAV_NVB490, EAV_NNN508 and EAV_NVH72 were resistant to rifampicin but EAV_VTKC53, which lacks arr , was only intermediately resistant.…”

Functional annotation of rhizospheric phageome of the wild plant species Moringa oleifera

“…Rifampin ADP-ribosyltransferase (Arr) is among enzystome serving in antibiotic inactivation due to the action of the encoding gene arr-1 of Mycobacterium smegmatis . Rifampin ADP-ribosyltransferase acts in catalyzing the ADP-ribosylation of rifampicin and other rifamycins, thus, inactivating them ( Figure 10 ) (Morgado et al, 2021 ). Rifampicin mainly acts in binding the B subunit of the RNA polymerase (e.g., RpoB) to inhibit the transcription initiation of bacterial genes and to facilitate the direct blocking of the elongating RNA (Albano et al, 2019 ).…”

Comparative Genomic Analysis of Antimicrobial-Resistant Escherichia coli from South American Camelids in Central Germany

“…The resistance element on contig42 of strain 20E0503 does not contain a plasmid replicon identifier. One strain, 20E0552, contained the rare arr-2 gene (Figure 3), an ADP-ribosyltransferase associated with resistance to rifampicin [48]. The contig encoding arr-2 contained four additional resistance genes, i.e., (i) aad1, mediating resistance against spectinomycin and streptomycin, (ii) blaOXA-10, mediating resistance against several β-lactams, including piperacillin/tazobactam, (iii) cmlA1, mediating resistance against chloramphenicol, and (iv) dfrA14, mediating resistance to trimethoprim (Figure 4).…”