FMNH2-dependent monooxygenases initiate catabolism of sulfonamides in Microbacterium sp. strain BR1 subsisting on sulfonamide antibiotics

Abstract

We report a cluster of genes encoding two monooxygenases (SadA and SadB) and one FMN reductase (SadC) that enable Microbacterium sp. strain BR1 and other Actinomycetes to inactivate sulfonamide antibiotics. Our results show that SadA and SadC are responsible for the initial attack of sulfonamide molecules resulting in the release of 4-aminophenol. The latter is further transformed into 1,2,4-trihydroxybenzene by SadB and SadC prior to mineralization and concomitant production of biomass. As the degradation products lack antibiotic activity, the presence of SadA will result in an alleviated bacteriostatic effect of sulfonamides. In addition to the relief from antibiotic stress this bacterium gains access to an additional carbon source when this gene cluster is expressed. As degradation of sulfonamides was also observed when Microbacterium sp. strain BR1 was grown on artificial urine medium, colonization with such strains may impede common sulfonamide treatment during co-infections with pathogens of the urinary tract. This case of biodegradation exemplifies the evolving catabolic capacity of bacteria, given that sulfonamide bacteriostatic are purely of synthetic origin. The wide distribution of this cluster in Actinomycetes and the presence of traA encoding a relaxase in its vicinity suggest that this cluster is mobile and that is rather alarming.

Subsistence and complexity of antimicrobial resistance on a community‐wide level

“…This strain was actually the first bacterium for which the genes and enzymes involved in the use of an antibiotic as a carbon and energy source had been characterized. The sad cluster is flanked by sequences encoding for mobile genetic elements (Ricken et al, 2017), as was also the case for Candidatus Leucobacter sulfamidivorax, where multiple copies of sadA were found to be flanked by single IS1380 family transposases (Reis et al, 2019). Moreover, the sulfonamide-resistant gene sul1 is commonly found in class 1 integrons and therefore known to be easily disseminated (Gillings, 2014).…”

“…On the one hand, this strain contains a modified dihydropteroate synthase sul1, a well-characterized sulfonamide resistance gene (Wise Jr. and Abou-Donia, 1975). On the other hand, it also bears the sad cluster, encoding for two monooxygenases (sadA and sadB) and a flavin reductase (sadC) respectively, which are responsible for the partial mineralization of sulfonamides (Ricken et al, 2017). This strain was actually the first bacterium for which the genes and enzymes involved in the use of an antibiotic as a carbon and energy source had been characterized.…”

Isolation of Bacterial Endophytes from Phalaris arundinacea and their Potential in Diclofenac and Sulfamethoxazole Degradation

“…The general potential of different Microbacterium species for the biodegradation of pharmaceuticals has already been highlighted (Kim et al 2011;Ricken et al 2013;Ricken et al 2017).…”

Electrical Characterization of Calcium Oxalate Hydrate in Urine

“…Many studies in the urolithiasis field aim at finding new and more effective treatments to reduce kidney stones formation, which can be done by either controlling the process of crystal formation in urine or by increasing the solubility of existing crystals. Such studies must be conducted on urine samples of known and controlled composition, and thus it is very common to observe the use of synthetic urine or the artificial introduction of crystals to simulate urine samples reflecting a urolithic illness [50][51][52][53][54][55]. Not using a real sample from individuals prone to kidney stone formation should not be a limitation of the study since we do not claim the ability to identify the type of salts forming the crystal, but rather we prove that insoluble calcium oxalate salt can be both detected and quantified.…”