Molecular mechanisms related to colistin resistance in enterobacteriaceae

Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance. © 2019 Aghapour et al

Molecular mechanisms related to colistin resistance in Enterobacteriaceae

Zahra Aghapour,1,2 Pourya Gholizadeh,3 Khudaverdi Ganbarov,4 Abed Zahedi Bialvaei,5 Suhad Saad Mahmood,6 Asghar Tanomand,7 Mehdi Yousefi,8 Mohammad Asgharzadeh,9 Bahman Yousefi,9 Hossein Samadi Kafil11Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Microbiology, Baku State University, Baku, Azerbaijan; 5Department of Microbiology, Iran University of Medical Sciences, Tehran, Iran; 6Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq; 7Department of Microbiology, Maragheh University of Medical Sciences, Maragheh, Iran; 8Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 9Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAbstract: Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.Keywords: colistin, Enterobacteriaceae, two-component system, lipid A, mcr gene

Oral Immunotherapy in Patients with IgE Mediated Reactions to Egg White: A Clinical Trial Study

Background: Oral immunotherapy (OIT) is under consideration as a promising treatment for desensitization of egg-allergic patients. The objective of this study was to assess the effectiveness of egg-white OIT in patients with IgE-mediated allergy to egg white and to compare the clinical and laboratory findings before and after OIT. Methods: This clinical trial was performed from February to August 2018 in Rasool e Akram Hospital, Tehran, Iran. Patients� selection criteria included a history of allergic symptoms, skin prick test (SPT) reactivity to egg white, and the inability to pass the Oral Food Challenge (OFC). Egg-white OIT was done for eight patients in the OIT group for 6 months while egg-white-free products were administrated for controls. The SPT reactivity, specific IgE, and IgG4 for egg white and ovomucoid were evaluated before and after OIT. Results: Hundred percent of the subjects in OIT group were desensitized and tolerated 40 cc raw egg white following 6-month maintenance whereas none of the controls was able to pass the OFC. The findings obtained from the evaluations indicated a significant decrease in the wheal size and specific IgE to egg white after OIT (P = .001). Furthermore, a significant decrease of IgE/IgG4 ratio to egg white was found in OIT group (P = .01). Conclusion: This OIT protocol was successful as all OIT patients were able to continue 6-month OIT process and the reaction threshold to egg white increased in the OIT group. Therefore, it could be regarded as an effective and safe protocol to treat egg-allergic patients. © 2020 Taylor & Francis Group, LLC

Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer � A comprehensive review from chemotherapy to immunotherapy

Breast cancer is the most frequently occurring cancer in women. Chemotherapy in combination with immunotherapy has been used to treat breast cancer. Atezolizumab targeting the protein programmed cell death-ligand (PD-L1) in combination with paclitaxel was recently approved by the Food and Drug Administration (FDA) for Triple-Negative Breast Cancer (TNBC), the most incurable type of breast cancer. However, the use of such drugs is restricted by genotype and is effective only for those TNBC patients expressing PD-L1. In addition, resistance to chemotherapy with drugs such as lapatinib, geftinib, and tamoxifen can develop. In this review, we address chemoresistance in breast cancer and discuss Akt as the master regulator of drug resistance and several oncogenic mechanisms in breast cancer. Akt not only directly interacts with the mitogen-activated protein (MAP) kinase signaling pathway to affect PD-L1 expression, but also has crosstalk with Notch and Wnt/β-catenin signaling pathways involved in cell migration and breast cancer stem cell integrity. In this review, we discuss the effects of tyrosine kinase inhibitors on Akt activation as well as the mechanism of Akt signaling in drug resistance. Akt also has a crucial role in mitochondrial metabolism and migrates into mitochondria to remodel breast cancer cell metabolism while also functioning in responses to hypoxic conditions. The Akt inhibitors ipatasertib, capivasertib, uprosertib, and MK-2206 not only suppress cancer cell proliferation and metastasis, but may also inhibit cytokine regulation and PD-L1 expression. Ipatasertib and uprosertib are undergoing clinical investigation to treat TNBC. Inhibition of Akt and its regulators can be used to control breast cancer progression and also immunosuppression, while discovery of additional compounds that target Akt and its modulators could provide solutions to resistance to chemotherapy and immunotherapy. © 2020 Elsevier Lt