Evolutionary origin of the class A and class C beta-lactamases.

The protein sequences of 18 class A beta-lactamases and 2 class C beta-lactamases were analyzed to produce a rooted phylogenetic tree using the DD peptidase of Streptomyces R61 as an outgroup. This tree supports the penicillin-binding proteins as the most likely candidate for the ancestoral origin of the class A and class C beta-lactamases, these proteins diverging from a common evolutionary origin close to the DD peptidase. The actinomycetes are clearly shown as the origin of the class A beta-lactamases found in other non-actinomycete species. The tree also divides the beta-lactamases from the Streptomyces into two subgroups. One subgroup is closer to the DD peptidase root. The other Streptomyces subgroup shares a common branch point with the rest of the class A beta-lactamases, showing this subgroup as the origin of the non-actinomycete class A beta-lactamases. The non-actinomycete class A beta-lactamase phylogenetic tree suggests a spread of these beta-lactamases by horizontal transfer from the Streptomyces into the non-actinomycete gram-positive bacteria and thence into the gram-negative bacteria. The phylogenetic tree of the Streptomyces class A beta-lactamases supports the possibility that horizontal transfer of class A beta-lactamases occurred within the Streptomyces.