Identification, Characterization, and Regulation of a Cluster of Genes Involved in Carbapenem Biosynthesis in Photorhabdus luminescens

The luminescent entomopathogenic bacterium Photorhabdus luminescens produces several yet-uncharacterized broad-spectrum antibiotics. We report the identification and characterization of a cluster of eight genes (named cpmA to cpmH) responsible for the production of a carbapenem-like antibiotic in strain TT01 of P. luminescens. The cpm cluster differs in several crucial aspects from other car operons. The level of cpm mRNA peaks during exponential phase and is regulated by a Rap/Hor homolog identified in the P. luminescens genome. Marker-exchange mutagenesis of this gene in the entomopathogen decreased antibiotic production. The luxS-like signaling mechanism of quorum sensing also plays a role in the regulation of the cpm operon. Indeed, luxS, which is involved in the production of a newly identified autoinducer, is responsible for repression of cpm gene expression at the end of the exponential growth phase. The importance of this carbapenem production in the ecology of P. luminescens is discussed.

发光昆虫病原细菌发光杆菌（Photorhabdus luminescens）可产生多种尚未被深入表征的广谱抗生素。本研究针对发光杆菌TT01菌株展开研究，成功鉴定并表征了其中负责合成一类碳青霉烯类类似抗生素的八基因簇，该基因簇被命名为cpmA至cpmH。cpm基因簇在多项关键特征上与其他car操纵子存在显著差异。cpm基因的mRNA转录水平在指数生长期达到峰值，其表达受发光杆菌基因组中已鉴定的Rap/Hor同源蛋白调控。对该昆虫病原菌中的该基因进行标记交换诱变后，抗生素的合成量显著降低。群体感应（quorum sensing）的luxS类信号通路同样参与cpm操纵子的调控：事实上，参与新型自诱导物合成的luxS基因，可在指数生长末期抑制cpm基因的表达。本研究还探讨了该碳青霉烯类抗生素的合成在发光杆菌生态中的重要意义。