Plasmid-mediated quinolone resistance (PMQR) and mutations in the topoisomerase genes of Salmonella enterica strains from Brazil

The objective of this study was to identify mutations in the Quinolone Resistance Determining sources Regions (QRDR) of the gyrA, gyrB, parC, and parE genes and to determine if any of the qnr variants or the aac(6')-Ib-cr variant were present in strains of Salmonella spp. isolated in Brazil. A total of 126 Salmonella spp. strains from epidemic (n = 114) and poultry (n = 12) origin were evaluated. One hundred and twelve strains (88.8%) were resistant to nalidixic acid (NAL) and 29 (23.01%) showed a reduced susceptibility to ciprofloxacin (Cip). The mutations identified were substitutions limited to the QRDR of the gyrA gene in the codons for Serine 83, Aspartate 87 and Alanine 131. The sensitivity to NAL seems to be a good phenotypic indication of distinguishing mutated and nonmutated strains in the QRDR, however the double mutation in gyrA did not cause resistance to ciprofloxacin. The qnrA1 and qnrB19 genes were detected, respectively, in one epidemic strain of S. Enteritidis and one strain of S. Corvallis of poultry origin. Despite previous detection of qnr genes in Brazil, this is the first report of qnr gene detection in Salmonella, and also the first detection of qnrB19 gene in this country. The results alert for the continuous monitoring of quinolone resistance determinants in order to minimize the emergence and selection of Salmonella spp. strains showing reduced susceptibility or resistance to quinolones.

Expression of DNA topoisomerase II alpha in melanocytic skin tumors

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcripion. These enzymes are also the cellular targets of new classes of chemotherapy agents termed topoisomerase poisons. These drugs are showing activity against a wide variety of solid human neoplasms. However, malignant melanoma [MM] is considered to be a chemotherapy refractory tumor and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. Because of the challenges in treating MM, we performed an immunohistochemical study of this group of neoplasms to search for the presence of molecular marker that might indicate tumor response to topo II alpha active drugs. Forty- five patients with melanocytic skin tumors were the subjects of this study. They included 29 patients suffering from benign nevi, 4 dysplastic nevi and 12 MM. Topoisomerase II alpha expression showed significantly higher expression in MM cases than benign melanocytic nevi. Dysplastic nevi showed topo II alpha expression midway between the two extremities. The difference between the 3 groups was statistically highly significant p<0.0001. In MM cases, topo II alpha expression was significantly correlated with lymph node metastasis [p=0.001], tumor ulceration [p=0.001], tumor thickness [p=0.0001], Clark's level [p=0.008], and nodular type melanoma [p=0.003] In conclusion, expression of topo II alpha provides a useful marker for proliferation and can differentiate between benign and malignant melanocytic skin tumors. While in MM cases, it is considered as a poor prognostic marker. As the enzyme topo II alpha is the target of a group of cytotoxic drugs. its expression might serve to predict the success of adjuvant cytotoxic therapy especially in advanced MM cases