Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus

A novel teicoplanin-associated operon termed tcaR-tcaA-tcaB was identified by Tn917-mediated insertional mutagenesis. Resistance to teicoplanin rose 4 -fold by insertional inactivation of tcaA or by deletion of the entire oper on. tcaA encodes a hypothetical transmembrane protein with a metal-binding motif, possibly a sensor-transducer. tcaB codes for a membrane-associated p rotein, which has sequence homologies to a bicyclomycin resistance protein. The two genes are preceded by tcaR encoding a putative regulator with sequ ence homologies to the transcriptional regulator MarR. The fact that tcaA i nactivation as well as deletion of tcaRAB produced the same increase in tei coplanin resistance confirmed the association of tcaRAB with teicoplanin su sceptibility. Cotransductional crosses showed that the level of teicoplanin resistance produced by these insertions was strain-dependent and that in t he methicillin-resistant strain COL, it was paired with a remarkable decrea se in methicillin resistance. This allowed to postulate that tcaRAB may be involved in some way in cell wall biosynthesis, and that teicoplanin may in teract with TcaA and/or TcaB either directly or indirectly. (C) 2000 Elsevi er Science B.V. All rights reserved.