UK; PhD Studentship School of Immunity & Infection
Characterisation of multi-drug and efflux inhibitor-resistance in Streptococcus pneumoniae.
Professor Laura Piddock/Professor Mark Pallen
Streptococcus pneumoniae is an important cause of respiratory and invasive infections. The prevalence of multidrug-resistant (MDR) S. pneumoniae is increasing in many countries. Chromosomally encoded efflux pumps confer innate resistance to multiple antibiotics. In S. pneumoniae two genes encoding ABC transporters (efflux pumps) patA and patB were shown to be over-expressed in a laboratory MDR mutant selected after antibiotic (ciprofloxacin) exposure (1,2).
Our most recent work indicates that increased expression of patA and patB occurs in ~50% of ciprofloxacin and/or MDR S. pneumoniae isolated from people. Use of efflux pump inhibitors provides a promising route to combating multidrug resistance, however we have also selected mutant S. pneumoniae resistant to the inhibitor reserpine (3). However, the cause of the increased expression of these two genes and concomitant enhanced efflux of multiple substrates has not been defined.
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