Response of Methicillin-Resistant Staphylococcus aureus to Amicoumacin A

Amicoumacin A exhibits strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in transcription of genes specifying several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which is induced in cells undergoing a collapse of Δψ. Consistent with the notion that LrgA modulates murein hydrolase activity, COL grown in the presence of amicoumacin A showed reduced autolysis, which was primarily caused by lower hydrolase activity. To gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by a serial passage method was carried out. Single point mutations generating codon substitutions were uncovered in ksgA (encoding RNA dimethyltransferase), fusA (elongation factor G), dnaG (primase), lacD (tagatose 1,6-bisphosphate aldolase), and SACOL0611 (a putative glycosyl transferase). The codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance reside in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability

Management of intramedullary tumours in children

Clinical presentation, diagnosis, surgical technique and results of 25 cases of intramedullary tumours in patients under 16 years of age are analyzed. Pre-operative spinal deformity was present in 9 patients. Surgery was performed in all. After multilaminectomy with preservation of the intervertebral joints, total removal of the lesion was achieved in 11 patients and subtotal removal in 14 others. After surgery, external immobilization lasting an average period of 5 years was instituted in all patients. Postoperative radiation therapy was performed in 11 cases (5 "high grade" astrocytomas, 5 ependymomas, 1 glioblastoma). There were 11 recurrences: 4 of which (2 ependymomas and 2 "low grade" astrocytomas) were treated surgically, 7 (5 "high grade" astrocytomas, 1 glioblastoma, 1 oligodendroglioma) with palliative radiation treatment. Six patients eventually developed postlaminectomy spinal deformities as diagnosed roentgenographically 6 to 50 months postoperatively. Of the 16 patients still alive, 7 did not present relevant neurological deficit, 1 presented a monoparesis, while the other 8 presented invalidating deficits. Surgical treatment did not differ from that employed in the intramedullary tumours in the adult: radical resection is indeed the optimal therapeutic origin. The risk of radiation therapy are greater in children: it is crucial to limit radiation therapy to only some histotypes. The incidence of spinal column deformity after multilevel laminectomy is greater in young patients. It is advisable to implement prevention of spinal deformities by postoperative external immobilization and constant follow-up so as to detect early changes of spinal stability