Genomic analysis of bifunctional Class C-Class D β-lactamases in environmental bacteria

Abstract

β-lactamases, which are found in several bacterial species and environments, are the main cause of resistance to β-lactams in Gram-negative bacteria. In 2009, a protein (LRA-13) with two β-lactamase domains (one class C domain and one class D domain) was experimentally characterised, and an extended action spectrum against β-lactams consistent with two functional domains was found. Here, we present the results of searches in the non-redundant NCBI protein database that revealed the existence of a group of homologous bifunctional β-lactamases in the genomes of environmental bacteria. These findings suggest that bifunctional β-lactamases are widespread in nature; these findings also raise concern that bifunctional β-lactamases may be transferred to bacteria of clinical importance through lateral gene transfer mechanisms.

Antibiotic Resistance Patterns of Pseudomonas spp. Isolated From Raw Milk Revealed by Whole Genome Sequencing

“…Although the total number of β-lactam resistance genes was high, the prevalence of each gene was low. Of the β-lactam resistance determinants, OCH-8 confers resistance to thirdgeneration cephalosporins (Alonso et al, 2017), whereas LRA-13 confers resistance to amoxicillin, ampicillin, cephalexin, and carbenicillin (Silveira et al, 2018). Penicillin-binding proteins (PBPs) are the physiological targets of β-lactam antibiotics (Spratt and Cromie, 1988), and mutations in the PBPs PBP1a, PBP1b, and PBP2, which were found to confer resistance to β-lactams (Di Guilmi et al, 2003;Stanhope et al, 2008;Unemo et al, 2012), have also been detected in four isolates ( Table 2 and Supplementary Table S3).…”

Quantification of β-lactamase producing bacteria in German surface waters with subsequent MALDI-TOF MS-based identification and β-lactamase activity assay

“…, Janthinobacterium lividum, and Massilia sp. in a study by Silveira et al (2018) [ 93 ]. Functional metallo-β-lactamase genes (type B carbapenemases) have already been described in Janthinobacterium lividum and Massilia oculi [ 94 , 95 ] and were shown to be phylogenetically related to acquired β-lactamases produced by clinical pathogens.…”

Elevating NagZ Improves Resistance to β-Lactam Antibiotics via Promoting AmpC β-Lactamase in Enterobacter cloacae

“…The sequence of AmpC β-lactamase is quite different from penicillin-typed β-lactamase (such as TEM-1), but it has a same amino acid of serine at its active site ( Pimenta et al, 2014 ). For classification, AmpC β-lactamase is classified to be class C based on Ambler method, while it is assigned to be group 1 according to Bush functional classification ( Silveira et al, 2018 ; Mack et al, 2019 ). The chromosomal AmpC β-lactamase is highly inducible in presence of some β-lactams, such as imipenem, cefoxitin, and clavulanate ( Jacoby, 2009 ; Gomez-Simmonds et al, 2018 ), but it is still not clear about underlying genetic regulation in AmpC β-lactamase associated with peptidoglycan recycling in E. cloacae clinical isolates.…”