Phylogenomic Analysis of β-Lactamase in Archaea and Bacteria Enables the Identification of Putative New Members

Abstract

Abstractβ-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI’s nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A–D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes.

Amoxicillin Administration Regimen and Resistance Mechanisms of Staphylococcus aureus Established in Tissue Cage Infection Model

“…It has also been widely used to treat infections caused by various bacteria in veterinary medicine. β-lactam antibiotic resistance exhibited by S. aureus is mainly due to the production of β-lactamase, which is mediated by plasmids to inhibit or hydrolyze the unique bactericidal structure of β-lactams and reduce the activity of antibacterial drugs (Keshri et al, 2018). β-lactamase confers resistance by facilitating the acquisition and stabilization of the mecA gene (Cohen and Sweeney, 1973; Katayama et al, 2003).…”

Promiscuous Enzyme Activity as a Driver of Allo and Iso Convergent Evolution, Lessons from the β-Lactamases

“…This pre-classification can be obtained via the similarity network [ 14 ] that is the most comprehensive clustering on the β-lactamases fold described so far ( Figure 1 ). This analysis, as well as other analyses [ 15 ], including ours [ 16 , 17 , 18 ], helped us to define several subfamilies of the metallo-β-lactamases, allowing us to perform precise analysis on some of them. We redefine the subfamily metallo-β-lactamase B3, glyoxalase 2, sulfur dioxygenase, metallo-β-lactamase B1/B2, TNP dehalogenase, and the archaea metallo-β-lactamase-like [ 13 , 15 , 16 , 17 ].…”

“…This analysis, as well as other analyses [ 15 ], including ours [ 16 , 17 , 18 ], helped us to define several subfamilies of the metallo-β-lactamases, allowing us to perform precise analysis on some of them. We redefine the subfamily metallo-β-lactamase B3, glyoxalase 2, sulfur dioxygenase, metallo-β-lactamase B1/B2, TNP dehalogenase, and the archaea metallo-β-lactamase-like [ 13 , 15 , 16 , 17 ]. To perform a robust phylogenetic analysis, we used a distance-based phylogenetic analysis since very few positions are conserved ( Figure 2 ).…”

Resistance to antibiotics of bacteria in tropical countries

“…10 Thus, β-lactam resistance genes are detected in all vertebrates, including humans, but also in archaea, which are not sensitive to β-lactams. 11 Hassell and colleagues' work 6 shows that in Nairobi, a city where antibiotic prescribing is extremely low, 5 the level of resistance of E coli is particularly high, not only in humans, but also in wildlife. This study must put into perspective a much less anthropocentric approach, integrating the fact that antibiotics are probably more than 3 billion years old, as are antibiotic-resistance enzymes, and that we can only understand, and therefore combat antibiotic resistance, if we have a more scientific vision of this world.…”