SummaryA novel growth phase-associated two-componenttype regulator, Fas (fibronectin/fibrinogen binding/ haemolytic activity/streptokinase regulator), of Streptococcus pyogenes was identified in the M1 genome sequence, based on homologies to the histidine protein kinase (HPK) and response regulator (RR) part of the Staphylococcus aureus Agr and Streptococcus pneumoniae Com quorum-sensing systems. The fas operon, present in all 12 tested M serotypes, was transcribed as polycystronic message (fasBCA) and contained genes encoding two potential HPKs (FasB and FasC) and one RR (FasA). Downstream of fasBCA, we identified a small 300 nucleotide monocistronic transcript, designated fasX, that did not appear to encode true peptide sequences. Measurements of luciferase promoter fusions revealed a growth phase-associated transcription of fasBCA and fasX, with peak activities during the late exponential phase. Insertional mutagenesis disrupting fasBCA and fasA led to a phenotype similar to agrnull mutations in S. aureus, with prolonged expression of extracellular matrix protein-binding adhesins and reduced expression of secreted virulence factors such as streptokinase and streptolysin S. In addition, fasX transcription was dependent on the RR FasA; however, deletion mutagenesis of fasX resulted in a similar phenotype to that of the fasBCA or fasA mutants. Complementation of the fasX deletion mutant, with the fasX gene expressed in trans from a plasmid, restored the wild-type fasBCA regulation pattern. This strongly suggested that fasX, a putative non-translated RNA, is the main effector molecule of the fas regulon. However, using spent culture supernatants from wild-type and fas mutant strains, we were not able to show an influence on the logarithmic growth phase expression of fas and dependent genes. Thus, despite structural and functional similarities between fas and agr, to date the fas operon appears not to be involved in group A streptococcal (GAS) quorum-sensing regulation.
In complex aortic coarctation or hypoplasia extraanatomic bypass grafts are expedient and effective procedures, especially for reoperation. Their use in the treatment of aneurysmal lesions remains an exception.
Bradyarrhythmias developing after Fontan-type operations impair the function of the univentricular heart causing fatigue, headaches, ascites, and protein-losing enteropathy (PLE). Transvenous inaccessibility, requiring epicardial implantation, accounts for the reluctance to implant a pacemaker (PM). Between 1997 and 2000, 24 patients (mean age 9.5 years, range 6 months to 19 years) with Fontan-type operations received DDD pacing systems with atrial steroid-eluting stitch-on electrodes (mean capture threshold 1.9 V/0.5 ms, range 0.4-3.5 V) and ventricular screw-in electrodes (mean capture threshold 1.7 V/0.5 ms, range 0.1-3 V). The systems were implanted at the time of conversion from atrio- to cavopulmonary connections in 5 patients, at the time of a total cavopulmonary Fontan operation in 6, and 1-50 months thereafter (mean = 18) in 13 patients. A right ventricular anatomy was present in 13 (54%) of 24 of PM recipients, versus 35% of the overall population. After a mean follow-up of 3.5 years, the PM were functioning in DDD mode in 23 of the 24 patients. Length of hospital stay in the ten patients who underwent repeat sternotomy was 5 days, without procedure related complications. In three children a repeat sternotomy was avoided by implanting the atrial electrodes during the Fontan operation. All patients improved clinically, including resolution of PLE in four patients. Bradyarrhythmias may lead to significant morbidity after Fontan-type operations. Electrophysiological evaluation is advised at follow-up. The indication for implantation of a DDD pacemaker system should be liberal. Placing atrial electrodes during the Fontan operation, especially in the presence of a right ventricular anatomy, avoids repeat sternotomy.
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