Transcriptome analysis of extended-spectrum ß-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus exposed to cefotaxime

Previous studies on bacterial response to antibiotics mainly focused on susceptible strains. Here we characterized the transcriptional responses of distinct cephalosporin-resistant bacteria of public health relevance to cefotaxime (CTX), a cephalosporin widely used in clinical practice. Adaptation to therapeutic concentrations of CTX (30 µg/ml) was investigated by RNA sequencing in mid-exponential phase cultures of a methicillin-resistant Staphylococcus aureus (MRSA) and two genetically diverse E. coli producing CTX-M-15 or CMY-2 β-lactamase following genome sequencing and annotation for each strain. MRSA showed the most notable adaptive changes in the transcriptome after exposure to CTX, mainly associated with cell envelope functions. This reprogramming coincided with a transient reduction in cell growth, which also occurred in the CMY-2-producing E. coli but not in the CTX-M-15-producing strain. Re-establishment of growth in the CMY-2 producer proceeded without any notable adaptive transcriptional response, while limited reprogramming of gene transcription was observed in the CTX-M-15 producer. Our data show that the transcriptional response of CTX-resistant bacteria to CTX depends on the bacterial species, level of resistance and resistance determinant involved. Gene products induced in the presence of CTX may play an essential role for bacterial survival during therapy and merit further investigation as possible targets for potentiating CTX

Outcomes of Ethnic Minority Groups with Node-Positive, Non-Metastatic Breast Cancer in Two Tertiary Referral Canters in Sydney, Australia

PURPOSE: There is a lack of information in ethnic minority groups with regard to presentation and treatment of early node-positive breast cancer. We carried out a retrospective study of patients referred to two tertiary cancer centers in South Western Sydney, both of which serve a high proportion of this ethnic minority population. PATIENTS AND METHODS: Women who had pathologically node-positive non-metastatic breast cancer (T1-3, N1-3, M0) diagnosed between 2003 and 2006 were studied, with variables of interest being tumor size, number of positive nodes, histological grade, hormone receptor status, age at diagnosis, country of birth and treatment. We compared the Asian and Western subgroups with regard to tumor characteristics, treatment and clinical outcomes. RESULTS: A total of 652 eligible patients were identified, with a median follow-up of 6.1 years. Women with Asian backgrounds (n = 125, 20%) were significantly younger at presentation (48 years versus 55 years, p-value <0.0001) and more likely to undergo mastectomy (53% versus 39%, p-value 0.0009) and chemotherapy (86% versus 72%, p-value 0.0063) than their non-Asian counterparts. Tumor stage, grade and receptor status were not statistically different between these two groups. There were also no differences in disease-free survival and overall survival, with medians of 12.7 and 14.8 years respectively. CONCLUSION: Women of Asian background are younger at diagnosis, which may reflect population epidemiology and likely results in higher uptake of chemotherapy. Higher mastectomy rates may be influenced by cultural factors. Future research is warranted to investigate potential differences in tumor biology, psychosocial, economic and cultural factors