M. Brandenberger et al., Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus, BBA-GEN SUB, 1523(2-3), 2000, pp. 135-139
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.