e-journal
Two routes of MexS‐MexT‐mediated regulation of MexEF‐OprN and MexAB‐OprM efflux pump expression in Pseudomonas aeruginosa
The NfxC‐type mutant of Pseudomonas aeruginosa produces the MexEF‐OprN efflux pump and downregulates
expression of the quorum‐sensing‐dependent efflux pump MexAB‐OprM and production of
virulence factors in the presence of an active transcriptional regulator, MexT. Consequently, these cells
are resistant to chloramphenicol and hypersusceptible to b‐lactam antibiotics. An upper negative
regulator, MexS, has been assumed to inactivate MexT in wild‐type strains, hence shutting down
production of the MexEF‐OprN pump. This observation was, however, reported in only one clinical
strain and not confirmed in well‐characterized laboratory strains. Moreover, it is not known whether
MexS is involved in the quorum‐sensing‐dependent regulation of virulence factor production. To assess
these issues, a plasmid carrying wild‐type mexS was introduced into three NfxC‐type mutants from
laboratory strains, which carry an impaired mexS and unimpaired mexT. Unexpectedly, all the
transformants produced an increased amount of MexEF‐OprN proteins. Three clinical NfxC strains
were similarly transformed and although MexEF‐OprN was undetectable in two of these strains, one
produced an increased amount of these proteins, similar to the laboratory strains. These results were
interpreted to mean that P. aeruginosa takes two separate routes inMexT‐mediated regulation of mexEFoprN
expression: the MexS‐bypassed pathway and MexS‐mediated pathway. On the other hand, the
transformants of both the laboratory and clinically derived NfxC‐type cells produced increased
amounts of MexAB‐OprM and virulence factors, suggesting that production of these proteins occurs via
the MexS‐mediated pathway.
Key words efflux pump, MexS, MexT, Pseudomonas aeruginosa.
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