Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

Contains fulltext : 97744.pdf (publisher's version ) (Open Access)BACKGROUND: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. RESULTS: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. CONCLUSIONS: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens

Visual field loss associated with vigabatrin: Quantification and relation to dosage

Purpose: To describe the correlation between visual field loss and the duration, dosage. and total amount of vigabatrin (VGB) medication in a group of patients with epilepsy. Co-medication of antiepileptic drugs (AEDs) and compliance were also studied. Methods: Ninety-two patients (53 male and 39 female) taking VGB medication in the past or the present, attending the Outpatient Epilepsy Clinic in Utrecht, were examined with the Goldmann perimeter. The amount of visual field loss was calculated by the Esterman grid method and by a new method, with which the percentage surface loss of the visual field is measured. A complete drug history was compiled, specifying the amount and duration of VGB medication. Concomitant AED medication was noted. Serum levels of AEDs were determined. Results: Linear regression showed the total amount of VGB as the most significant parameter to predict visual field loss (p <0.001). Further, men were more affected than women (p = 0.026). Compliance was good, and other AEDs did not influence the results. Conclusions: Because prolonged use of VGB medication is correlated with the amount of visual field loss, VGB should be prescribed only when there are no alternatives. In such cases, we recommend an examination of the peripheral visual field before starting therapy and a repeated examination every 6 months