The adaptation of Corynebacterium glutamicum to acetate as a carbon and energy source involves transcriptional regulation of the pta-ack operon coding for the acetate-activating enzymes phosphotransacetylase and acetate kinase and of the aceA and aceB genes coding for the glyoxylate cycle enzymes isocitrate lyase and malate synthase, respectively. Deletion and mutation analysis of the respective promoter regions led to the identification of highly conserved 13-bp motifs (AA/GAACTTTGCAAA) as cis-regulatory elements for expression of the pta-ack operon and the aceA and aceB genes. By use of DNA affinity chromatography, a 53-kDa protein specifically binding to the promoter/operator region of the pta-ack operon was purified. Mass spectrometry and peptide mass fingerprinting identified the protein as a putative transcriptional regulator (which was designated RamB). Purified His-tagged RamB protein was shown to bind specifically to both the pta-ack and the aceA/aceB promoter/operator regions. Directed deletion of the ramB gene in the genome of C. glutamicum resulted in mutant strain RG1. Whereas the wild type of C. glutamicum showed high-level specific activities of acetate kinase, phosphotransacetylase, isocitrate lyase, and malate synthase when grown on acetate and low-level specific activities when grown on glucose as sole carbon and energy sources, mutant RG1 showed high-level specific activities with all four enzymes irrespective of the substrate. Comparative transcriptional cat fusion experiments revealed that this deregulation takes place at the level of transcription. The results indicate that RamB is a negative transcriptional regulator of genes involved in acetate metabolism of C. glutamicum.

AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.

Expression profiling of Corynebacterium glutamicum in comparison to a derivative deficient in the transcriptional regulator AtlR (previously known as SucR or MtlR) revealed eight genes showing more than 4-fold higher mRNA levels in the mutant. Four of these genes are located in the direct vicinity of the atlR gene, i.e., xylB, rbtT, mtlD, and sixA, annotated as encoding xylulokinase, the ribitol transporter, mannitol 2-dehydrogenase, and phosphohistidine phosphatase, respectively. Transcriptional analysis indicated that atlR and the four genes are organized as atlR-xylB and rbtT-mtlD-sixA operons. Growth experiments with C. glutamicum and C. glutamicum ⌬atlR, ⌬xylB, ⌬rbtT, ⌬mtlD, and ⌬sixA derivatives with sugar alcohols revealed that (

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In order to investigate the effects of 193nm excimer laser radiation on comeal wound healing 5bovine comeas were treated with subablative and ablative 193nm Excimer laser radiation, by simple light exposure and mechanial ablation of the corneal tissue or not treated. The comeas were metabolically labelled with a [35S]-labelling reagent. The proteoglycans were then extracted and radioactivity was measured with a liquid scintillation spectrometer. Corneas after ablative 193nm excimer laser radiation and after mechanical ablation had less radioactivity incorporated but had also less comeal tissue.

Eosinophilia-Myalgia-Syndrome (EMS), a newly recognized illness, was described first in October 1989, when it formed an epidemic in the USA and later also in Europe. In the meantime, ingestion of L-tryptophan containing products has been recognized to trigger this syndrome, but the pathophysiological basics are still subject to speculation. Often starting with a flu-like period, the disease is dominated by dermatologic (fasciitis) and neurologic (neuropathy, myopathy) symptoms in the subsequent stages. Reporting on an own case and reviewing the literature, clinicopathological aspects and the problems of treatment are discussed. In contrast with the majority of published cases, which showed predominance of axonal damage, our patient displayed the clinical and electro-physiologic characteristics of demyelinating neuropathy.