BMS Faculty Feature: Keith Derbyshire

Portrait of Keith Derbyshire

As a graduate student, Keith Derbyshire studied plasmid conjugation in E. coli, a mechanism of horizontal gene transfer used by bacteria. Typical bacteria have both chromosomal DNA, which carry essential genes, and smaller circular plasmid DNAs, which carry genes for their own replication and often accessory genes, including those mediating conjugation and antibiotic resistance. Conjugation allows bacteria to transfer plasmid DNA to adjacent bacteria, and can therefore result in the spread of antibiotic resistance.

In his faculty position at the Wadsworth Center, Derbyshire intended to develop conjugation as a molecular biology tool to study the Mycobacterium species. DNA transfer had already been shown in Mycobacterium smegmatis. Derbyshire applied his previous experience with E. coli to M. smegmatis to determine the mechanism of transfer. His lab set out to identify the plasmid that allowed conjugative DNA transfer in Mycobacteria. There was one hitch: M. smegmatis had no plasmid DNA! Unexpected results like this are “what makes science fun,” says Derbyshire.

What followed were experiments showing that M. smegmatis could transfer chromosomal DNA without plasmids, and the discovery of distributive conjugal transfer. This mechanism transfers small and large pieces of chromosomal DNA from one M. smegmatis strain to another, and the newly acquired DNA is recombined into the recipient bacterial genome. The Derbyshire group had found an entirely new conjugation system.

In 2019, Derbyshire was named a fellow of both the American Association for the Advancement of Science and the American Academy of Microbiology. The awards recognize his scientific contributions to the fields of bacterial conjugation and transposition. Derbyshire says, “It’s all thanks to the people in my lab who have contributed all along.” Derbyshire also cites the amazing scientific community formed by the Wadsworth Center, where research and diagnostic labs can collaborate to focus on human health.