The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate

<p>Abstract</p> <p>Background</p> <p>Secondary metabolism in <it>Serratia </it>sp. ATCC 39006 (<it>Serratia </it>39006) is controlled via a complex network of regulators, including a LuxIR-type (SmaIR) quorum sensing (QS) system. Here we investigate the molecular mechanism by which phosphate limitation controls biosynthesis of two antibiotic secondary metabolites, prodigiosin and carbapenem, in <it>Serratia </it>39006.</p> <p>Results</p> <p>We demonstrate that a mutation in the high affinity phosphate transporter <it>pstSCAB-phoU</it>, believed to mimic low phosphate conditions, causes upregulation of secondary metabolism and QS in <it>Serratia </it>39006, via the PhoBR two-component system. Phosphate limitation also activated secondary metabolism and QS in <it>Serratia </it>39006. In addition, a <it>pstS </it>mutation resulted in upregulation of <it>rap</it>. Rap, a putative SlyA/MarR-family transcriptional regulator, shares similarity with the global regulator RovA (regulator of virulence) from <it>Yersina </it>spp. and is an activator of secondary metabolism in <it>Serratia </it>39006. We demonstrate that expression of <it>rap</it>, <it>pigA-O </it>(encoding the prodigiosin biosynthetic operon) and <it>smaI </it>are controlled via PhoBR in <it>Serratia </it>39006.</p> <p>Conclusion</p> <p>Phosphate limitation regulates secondary metabolism in <it>Serratia </it>39006 via multiple inter-linked pathways, incorporating transcriptional control mediated by three important global regulators, PhoB, SmaR and Rap.</p

Analysis of long-term hearing gains after stapes surgery with piston reconstruction for otosclerosis

ObjectivesWe sought to assess the postoperative hearing gains at individual frequencies after stapes surgery with piston reconstruction for clinical otosclerosis.MethodsWe analyzed the air conduction (AC) hearing gains at various audiometric frequencies in a sample of 1,168 stapes procedures with piston reconstruction performed on 911 strictly consecutive patients by one surgeon between 1963 and 1979. Assiduous follow-up of patients was attempted for at least 10 years. The audiometric results over time were stored for computer analysis.ResultsThe mean AC gain over the speech frequencies (0.5, 1,2, and 3 kHz) was 35.5 dB at 1 year after operation, and the rate of deterioration over the next 19 years was 0.58 dB/y.ConclusionsThe picture to emerge from the analysis is clear. The mean AC gain is maximal at nearly 40 dB for the audiometric frequencies of 0.25, 0.5, and 1 kHz. The mean AC gain at any given time after operation decreases with increasing frequency, at least for frequencies of > or = 1 kHz. For any frequency there is, with few exceptions, a significant decrease in the AC gain from one time period to the next.Ronald Edward Gristwood, William Norman Venable