A PHEROMONE-INDEPENDENT CARR PROTEIN CONTROLS CARBAPENEM ANTIBIOTIC-SYNTHESIS OPPORTUNISTIC HUMAN PATHOGEN SERRATIA-MARCESCENS

Strain ATCC 39006 of Serratia marcescens makes the same carbapenem, (5 R)-carbapen-2-em-3-carboxylic acid (Car), as the Erwinia carotovora st rain GS101. Unlike E. carotovora, where the onset of production occurs in the late-exponential phase of growth in response to the accumulati on of the small diffusible pheromone N-(3-oxohexanoyl)-L-homoserine la ctone (OHHL), in S. marcescens carbapenem is produced throughout the g rowth phase and does not appear to involve any diffusible pheromone mo lecule. Two cosmids capable of restoring antibiotic production in E. c arotovora group I carbapenem mutants were isolated from an S. marcesce ns gene library. These cosmids were shown to contain a homologue of th e E. carotovora carR gene, encoding a CarR protein with homology to th e LuxR family of transcriptional regulators. The S. marcescens carR wa s subcloned and shown to be capable of complementing in trans, in the absence of OHHL, an E. carotovora carR carl double mutant, releasing t he heterologous E. carotovora host from pheromone dependence for carba penem production. The apparent OHHL-independence of the S. marcescens CarR explains the constitutive nature of carbapenem production in this strain of S. marcescens.