The rapid spread of carbapenem-resistant Enterobacteriaceae
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chro...
Source: Drug Resistance Updates - September 18, 2016 Category: Drugs & Pharmacology Authors: Robert F. Potter, Alaric W. D ’souza, Gautam Dantas Tags: Invited review Source Type: research
Plasmid-mediated quinolone resistance: Two decades on
After two decades of the discovery of plasmid-mediated quinolone resistance (PMQR), three different mechanisms have been associated to this phenomenom: target protection (Qnr proteins, including several families with multiple alleles), active efflux pumps (mainly QepA and OqxAB pumps) and drug modification [AAC(6 ′)-Ib-cr acetyltransferase]. PMQR genes are usually associated with mobile or transposable elements on plasmids, and, in the case of qnr genes, are often incorporated into sul1-type integrons. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - September 8, 2016 Category: Drugs & Pharmacology Authors: Jos é Manuel Rodríguez-Martínez, Jesús Machuca, María Eliecer Cano, Jorge Calvo, Luis Martínez-Martínez, Alvaro Pascual Source Type: research
The semaphorins and their receptors as modulators of tumor progression
The semaphorins were initially characterized as repulsive axon guidance factors. However, they are currently also recognized as important regulators of diverse biological processes which include regulation of immune responses, angiogenesis, organogenesis, and a variety of additional physiological and developmental functions. The semaphorin family consists of more than 20 genes divided into seven subfamilies, all of which contain the sema domain signature. They usually transduce signals by activation of receptors belonging to the plexin family, either directly, or indirectly following the binding of some semaphorins to rece...
Source: Drug Resistance Updates - August 27, 2016 Category: Drugs & Pharmacology Authors: Gera Neufeld, Yelena Mumblat, Tanya Smolkin, Shira Toledano, Inbal Nir-Zvi, Keren Ziv, Ofra Kessler Source Type: research
Renew or Die: The molecular mechanisms of peptidoglycan recycling and antibiotic resistance in Gram-negative pathogens
Antimicrobial resistance is one of the most serious health threats. Cell-wall remodeling processes are tightly regulated to warrant bacterial survival and in some cases are directly linked to antibiotic resistance. Remodeling produces cell-wall fragments that are recycled but can also act as messengers for bacterial communication, as effector molecules in immune response and as signaling molecules triggering antibiotic resistance. This review is intended to provide state-of-the-art information about the molecular mechanisms governing this process and gather structural information of the different macromolecular machineries...
Source: Drug Resistance Updates - July 28, 2016 Category: Drugs & Pharmacology Authors: Teresa Dom ínguez-Gil, Rafael Molina, Martín Alcorlo, Juan A. Hermoso Source Type: research
Antibiotic Resistance in Burkholderia Species
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include B. mallei and B. pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. B. cenocepacia, B. multivorans, and B. vietnamiensis belong to the B. cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - July 28, 2016 Category: Drugs & Pharmacology Authors: Katherine A. Rhodes, Herbert P. Schweizer Source Type: research
Old drugs, novel ways out: Drug resistance toward cytotoxic chemotherapeutics
Efficacy of chemotherapy in the treatment of distinct malignancies is often hampered by drug resistance arising in the tumor. Understanding the molecular basis of drug resistance and translating this knowledge into personalized treatment decisions can enhance therapeutic efficacy and even curative outcome. Over the years, multiple drug resistance mechanisms have been identified that enable tumors to cope with the damage instigated by a specific drug or group of anti-tumor agents. Here we provide an overview of the molecular pathways leading to resistance against conventional anti-cancer drugs, with emphasis on the utility ...
Source: Drug Resistance Updates - July 14, 2016 Category: Drugs & Pharmacology Authors: Ruud H. Wijdeven, Baoxu Pang, Yehuda G. Assaraf, Jacques Neefjes Source Type: research
Old drugs, novel ways out: drug resistance towards cytotoxic chemotherapeutics
Efficacy of chemotherapy in the treatment of distinct malignancies is often hampered by drug resistance arising in the tumor. Understanding the molecular basis of drug resistance and translating this knowledge into personalized treatment decisions can enhance therapeutic efficacy and even curative outcome. Over the years, multiple drug resistance mechanisms have been identified that enable tumors to cope with the damage instigated by a specific drug or group of anti-tumor agents. Here we provide an overview of the molecular pathways leading to resistance against conventional anti-cancer drugs, with emphasis on the utility ...
Source: Drug Resistance Updates - July 14, 2016 Category: Drugs & Pharmacology Authors: Ruud H Wijdeven, Baoxu Pang, Yehuda G. Assaraf, Jacques Neefjes Source Type: research
The pharmacogenomics of drug resistance to protein kinase inhibitors
Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. (Source...
Source: Drug Resistance Updates - July 4, 2016 Category: Drugs & Pharmacology Authors: Nancy K. Gillis, Howard L. McLeod Source Type: research
Folylpoly- γ-glutamate synthetase: A key determinant of folate homeostasis and antifolate resistance in cancer
Mammalians are devoid of autonomous biosynthesis of folates and hence must obtain them from the diet. Reduced folate cofactors are B9-vitamins which play a key role as donors of one-carbon units in the biosynthesis of purine nucleotides, thymidylate and amino acids as well as in a multitude of methylation reactions including DNA, RNA, histone and non-histone proteins, phospholipids, as well as intermediate metabolites. The products of these S-adenosylmethionine (SAM)-dependent methylations are involved in the regulation of key biological processes including transcription, translation and intracellular signaling. (Source: D...
Source: Drug Resistance Updates - July 3, 2016 Category: Drugs & Pharmacology Authors: Shachar Raz, Michal Stark, Yehuda G. Assaraf Source Type: research
Folylpoly-γ-glutamate synthetase: A key determinant of folate homeostasis and antifolate resistance in cancer
Mammalians are devoid of autonomous biosynthesis of folates and hence must obtain them from the diet. Reduced folate cofactors are B9-vitamins which play a key role as donors of one-carbon units in the biosynthesis of purine nucleotides, thymidylate and amino acids as well as in a multitude of methylation reactions including DNA, RNA, histone and non-histone proteins, phospholipids, as well as intermediate metabolites. The products of these S-adenosylmethionine (SAM)-dependent methylations are involved in the regulation of key biological processes including transcription, translation and intracellular signaling. (Source: D...
Source: Drug Resistance Updates - July 3, 2016 Category: Drugs & Pharmacology Authors: Shachar Raz, Michal Stark, Yehuda G. Assaraf Source Type: research
Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials
Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - June 29, 2016 Category: Drugs & Pharmacology Authors: Sara Hernando-Amado, Paula Blanco, Manuel Alcalde-Rico, Fernando Corona, Jose A. Reales-Calder ón, María B. Sánchez, José L. Martínez Tags: Invited review Source Type: research
