RESUMO
ABSTRACT: Staphylococcus spp. are bacteria involved in human and animal infections. They are resistant to antimicrobials and have become a major public health concern. In recent years, there has been a significant increase in methicillin-resistant Staphylococcus strains and vancomycin is the drug of choice for the treatment of such isolates. However, the minimum inhibitory concentration (MIC) of vancomycin necessary to combat this microorganism has been showing an increase. The aim of the present study was to determine the susceptibility profile of the Staphylococcus spp. of domestic and wild animals to vancomycin, using the microdilution in broth and E-test® techniques, as well as comparing the results of both tests. Of the 50 isolates tested, 47 (94 %) were sensitive to vancomycin in the microdilution and 43 (86 %) were sensitive to vancomycin in the E-test®. Seven (14 %) isolates had an intermediate result showing a risk to public health since the detection of these isolates may precede the occurrence of isolates resistant to vancomycin. In addition, the mecA gene was detected in 78 % of the tested samples. Six of the seven isolates with intermediate resistance to vancomycin were carriers of the mecA gene, showing that these isolates had a potential risk of becoming resistant. Thus, control measures must be taken to prevent the spread of these isolates with intermediate resistance and preserve the effectiveness of this antimicrobial for the treatment of infections caused by multiresistant Staphylococcus spp.
RESUMO: Staphylococcus spp. são bactérias envolvidas em infecções de humanos e animais, resistentes a antimicrobianos e tem se tornado uma grande preocupação em saúde pública. Nos últimos anos houve um aumento significativo de Staphylococcus resistentes à meticilina e a vancomicina é a droga de escolha para o tratamento desses isolados, porém vem apresentando elevação nos valores de Concentração Inibitória Mínima (CIM) necessários para combater este microrganismo. O objetivo do presente trabalho foi determinar o perfil de suscetibilidade à vancomicina para isolados de Staphylococcus spp. de animais domésticos e silvestres pelas técnicas de Microdiluição em caldo e E-test®, bem como comparar os resultados de ambos os testes. Dos 50 isolados testados 47 (94%) foram sensíveis à vancomicina na Microdiluição e 43 (86%) foram sensíveis à vancomicina no E-test®. Sete (14%) isolados tiveram resultado intermediário demonstrando um risco à saúde pública visto que a detecção destes isolados pode preceder a ocorrência de isolados resistentes à vancomicina. Ademais o gene mecA foi detectado em 78% das amostras testadas, sendo que dos sete isolados com resistência intermediária à vancomicina, seis eram portadores do gene mecA, evidenciando que esses isolados possuem potencial risco de se tornarem resistentes. Dessa forma medidas de controle devem ser tomadas para evitar a propagação destes isolados com resistência intermediária e preservar a eficácia deste antimicrobiano para o tratamento de infecções causadas por Staphylococcus multirresitentes.
RESUMO
The relationship between human cytomegalovirus (HCMV) and tumours has been extensively investigated, mainly in glioblastoma multiforme (GBM), a malignant tumour of the central nervous system with low overall survival rates. Several reports have demonstrated the presence of HCMV in GBM, although typically restricted to a low number of cells, and studies have indicated that viral proteins have the ability to dysregulate cellular processes and increase tumour malignancy. Treatment of GBM involves the use of the chemotherapeutic agents temozolomide (TMZ) and carmustine (bis-chloroethylnitrosourea, BCNU), which lead to the attachment of adducts to the DNA backbone, causing errors during replication and consequent cell death. It is known that HCMV infection can modulate DNA repair pathways, but what effects the virus may exhibit during chemotherapy are unknown. Here we approach this question by analysing HCMV infection and viral protein accumulation in GBM cell lines with different genotypes and their response to TMZ and BCNU in the presence of the virus. We demonstrate that A172, TP365MG and U251MG GBM cells are efficiently infected by both low-passage (TB40E) and high-passage (AD169) HCMV strains. However, the GBM cell lines vary widely in their permissiveness to viral gene expression and exhibit very different patterns of immediate early, early and late protein accumulation. HCMV reduces the viability of permissive GBM cells in a multiplicity-dependent manner in both the absence and presence of TMZ or BNCU. In sum, we demonstrate that GBM cell lines are equally susceptible but differentially permissive to infection by both low- and high-passage strains of HCMV. This observation not only indicates that viral replication is largely controlled by cellular factors in this system, but also provides a possible explanation for why viral gene products are only found in a subset of cells in GBM tumours. Furthermore, we conclude that the virus does not confer increased resistance to chemotherapeutic drugs in various GBM cell lines, but instead reduces tumour cell viability. These results highlight that the oncomodulatory potential of HCMV is not limited to cancer-promoting activities, but also includes adverse effects on tumour cell proliferation or survival.
