Diversity, epidemiology, and genetics of class D beta-lactamases

Abstract

Class D beta-lactamase-mediated resistance to beta-lactams has been increasingly reported during the last decade. Those enzymes also known as oxacillinases or OXAs are widely distributed among Gram negatives. Genes encoding class D beta-lactamases are known to be intrinsic in many Gram-negative rods, including Acinetobacter baumannii and Pseudomonas aeruginosa, but play a minor role in natural resistance phenotypes. The OXAs (ca. 150 variants reported so far) are characterized by an important genetic diversity and a great heterogeneity in terms of beta-lactam hydrolysis spectrum. The acquired OXAs possess either a narrow spectrum or an expanded spectrum of hydrolysis, including carbapenems in several instances. Acquired class D beta-lactamase genes are mostly associated to class 1 integron or to insertion sequences.

FIG. 1.

Amino acid alignment of 13 representative class D β-lactamases from the different groups. Stars indicate residues identical among all the amino acid sequences. Amino acid motifs which are well conserved (even if possibly variable) among class D β-lactamases are indicated by gray shading. Numbering is according to DBL numbering (32).

FIG. 2.

Dendrogram obtained for 73 class D β-lactamases by using Phylip (ClustalW). Branch lengths are to scale and proportional to the number of amino acid changes. The distance along the vertical axis has no significance. The different clusters identified allowed the identification of nine main groups, considering that proteins from the same group have more than 80% amino acid identity.