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Molecular Biology Reports Oct 2021Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality... (Review)
Review
Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality rate because strains resistant to antimicrobial agents are a major challenge for physicians and healthcare workers regarding the eradication of either hospital or community-based infections. These strains with emerging resistance are a serious issue for patients in the intensive care unit (ICU). Antibiotic resistance has increased because of the acquirement of mobile genetic elements such as transposons, plasmids, and integrons and causes the prevalence of multidrug resistance strains (MDR). In addition, an increase in carbapenem resistance, which is used as last line antibiotic treatment to eliminate infections with multidrug-resistant Gram-negative bacteria, is a major concern. Carbapenems resistant A. baumannii (CR-Ab) is a worldwide problem. Because these strains are often resistant to all other commonly used antibiotics. Therefore, pathogenic multi-drug resistance A. baumannii (MDR-Ab) associated infections become hard to eradicate. Plasmid-mediated resistance causes outbreaks of extensive drug-resistant. A. baumannii (XDR-Ab). In addition, recent outbreaks relating to livestock and community settings illustrate the existence of large MDR-Ab strain reservoirs within and outside hospital settings. The purpose of this review, proper monitoring, prevention, and treatment are required to control (XDR-Ab) infections. Attachment, the formation of biofilms and the secretion of toxins, and low activation of inflammatory responses are mechanisms used by pathogenic A. baumannii strain. This review will discuss some aspects associated with antibiotics resistance in A. baumannii as well as cover briefly phage therapy as an alternative therapeutic treatment.
Topics: Acinetobacter baumannii; Biofilms; Drug Resistance, Multiple, Bacterial; Hospitals; Host-Pathogen Interactions; Humans; Quorum Sensing; Virulence
PubMed: 34460060
DOI: 10.1007/s11033-021-06690-6 -
Current Drug Targets 2020The existence of the multi-drug resistant (MDR) pathogenic fungus, Candida auris came to light in 2009. This particular organism is capable of causing nosocomial... (Review)
Review
The existence of the multi-drug resistant (MDR) pathogenic fungus, Candida auris came to light in 2009. This particular organism is capable of causing nosocomial infections in immunecompromised persons. This pathogen is associated with consistent candidemia with high mortality rate and presents a serious global health threat. Whole genome sequence (WGS) investigation detected powerful phylogeographic Candida auris genotypes which are specialized to particular geological areas indicating dissemination of particular genotype among provinces. Furthermore, this organism frequently exhibits multidrug-resistance and displays an unusual sensitivity profile. Identification techniques that are commercialized to test Candida auris often show inconsistent results and this misidentification leads to treatment failure which complicates the management of candidiasis. Till date, Candida auris has been progressively recorded from several countries and therefore its preventive control measures are paramount to interrupt its transmission. In this review, we discussed prevalence, biology, drug-resistance phenomena, virulence factors and management of Candida auris infections.
Topics: Adolescent; Adult; Aged; Antifungal Agents; Candida; Candidiasis; Child; Child, Preschool; Cross Infection; Drug Resistance, Multiple, Fungal; Female; Global Health; Humans; Infant; Infant, Newborn; Infection Control; Male; Middle Aged; Prevalence; Risk Factors; Virulence Factors; Young Adult
PubMed: 31549952
DOI: 10.2174/1389450120666190924155631 -
Accounts of Chemical Research May 2021""Antimicrobial resistance (AMR), is one of the most paramount health perils that has emerged in the 21st century. The global increase in drug-resistant strains of... (Review)
Review
""Antimicrobial resistance (AMR), is one of the most paramount health perils that has emerged in the 21st century. The global increase in drug-resistant strains of various bacterial pathogens prompted the World Health Organization (WHO) to develop a priority list of AMR pathogens. (), an acid-fast bacillus that causes tuberculosis (TB), merits being one of the highest priority pathogens on this list since drug-resistant TB (DR-TB) accounts for ∼29% of deaths attributable to AMR. In recent years, funded collaborative efforts of researchers from academia, not-for-profit virtual R&D organizations and industry have resulted in the continuous growth of the TB drug discovery and development pipeline. This has so far led to the accelerated regulatory approval of bedaquiline and delamanid for the treatment of DR-TB. However, despite the availability of drug regimes, the current cure rate for multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) treatment regimens is 50% and 30%, respectively. It is to be noted that these regimens are administered over a long duration and have a serious side effect profile. Coupled with poor patient adherence, this has led to further acquisition of drug resistance and treatment failure. There is therefore an urgent need to develop new TB drugs with novel mechanism of actions (MoAs) and associated regimens.This Account recapitulates drug resistance in TB, existing challenges in addressing DR-TB, new drugs and regimens in development, and potential ways to treat DR-TB. We highlight our research aimed at identifying novel small molecule leads and associated targets against TB toward contributing to the global TB drug discovery and development pipeline. Our work mainly involves screening of various small molecule chemical libraries in phenotypic whole-cell based assays to identify hits for medicinal chemistry optimization, with attendant deconvolution of the MoA. We discuss the identification of small molecule chemotypes active against and subsequent structure-activity relationships (SAR) and MoA deconvolution studies. This is followed by a discussion on a chemical series identified by whole-cell cross-screening against , for which MoA deconvolution studies revealed a pathway that explained the lack of in vivo efficacy in a mouse model of TB and reiterated the importance of selecting an appropriate growth medium during phenotypic screening. We also discuss our efforts on drug repositioning toward addressing DR-TB. In the concluding section, we preview some promising future directions and the challenges inherent in advancing the drug pipeline to address DR-TB.
Topics: Animals; Antitubercular Agents; Drug Resistance, Multiple; Humans; Mycobacterium tuberculosis; Structure-Activity Relationship; Tuberculosis
PubMed: 33886255
DOI: 10.1021/acs.accounts.0c00878 -
Expert Review of Anti-infective Therapy 2015Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two... (Comparative Study)
Comparative Study Review
Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two antibiotics were previously regarded to be largely equivalent, due to similarities in their chemical structure and spectrum of activity. In recent years, several pertinent differences, especially in terms of potency and disposition, have been revealed between polymyxin B and colistin. These differences are mainly attributed to the fact that polymyxin B is administered parenterally in its active form, while colistin is administered parenterally as an inactive pro-drug, colistimethate. In this review, we summarize the similarities and differences between polymyxin B and colistin. We also discuss the potential clinical implications of these findings, and provide our perspectives on how polymyxins should be employed to preserve their utility in this era of multi-drug resistance.
Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxin B
PubMed: 26488563
DOI: 10.1586/14787210.2015.1093933 -
Advances in Experimental Medicine and... 2018The rapid evolution of antibiotic resistance in Clostridium difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matter... (Review)
Review
The rapid evolution of antibiotic resistance in Clostridium difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matter of concern for public health. Antibiotic resistance plays an important role in driving C. difficile epidemiology. Emergence of new types is often associated with the emergence of new resistances and most of epidemic C. difficile clinical isolates is currently resistant to multiple antibiotics. In particular, it is to worth to note the recent identification of strains with reduced susceptibility to the first-line antibiotics for CDI treatment and/or for relapsing infections. Antibiotic resistance in C. difficile has a multifactorial nature. Acquisition of genetic elements and alterations of the antibiotic target sites, as well as other factors, such as variations in the metabolic pathways and biofilm production, contribute to the survival of this pathogen in the presence of antibiotics. Different transfer mechanisms facilitate the spread of mobile elements among C. difficile strains and between C. difficile and other species. Furthermore, recent data indicate that both genetic elements and alterations in the antibiotic targets can be maintained in C. difficile regardless of the burden imposed on fitness, and therefore resistances may persist in C. difficile population in absence of antibiotic selective pressure.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 29383668
DOI: 10.1007/978-3-319-72799-8_9 -
Accounts of Chemical Research Jul 2021
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple; Humans
PubMed: 34225457
DOI: 10.1021/acs.accounts.1c00246 -
Journal of Inorganic Biochemistry Dec 2022Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial... (Review)
Review
Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial resistance to currently available antimicrobials. Metal nanoparticles represent a new perspective in treating AMR due to their unique mechanisms, such as disrupting bacterial cell membrane potential and integrity, biofilm inhibition, reactive oxygen species (ROS) formation, enhancing host immune responses, and inhibiting RNA and protein synthesis by inducing intracellular processes. Metal nanoparticles (MNPs) properties such as size, shape, surface functionalization, surface charges, and co-encapsulated drug delivery capability all play a role in determining their potential against multidrug-resistant bacterial infections. Silver, gold, zinc oxide, selenium, copper, cobalt, and iron oxide nanoparticles have recently been studied extensively against multidrug-resistant bacterial infections. This review aims to provide insight into the size, shape, surface properties, and co-encapsulation of various MNPs in managing multidrug-resistant bacterial infections.
Topics: Humans; Anti-Bacterial Agents; Metal Nanoparticles; Drug Resistance, Multiple, Bacterial; Bacterial Infections; Bacteria; Nanoparticles; Microbial Sensitivity Tests
PubMed: 36122430
DOI: 10.1016/j.jinorgbio.2022.111938 -
Gene Mar 2023Oncogenes together with tumor suppresser genes are confirmed to regulate tumor phenotype in human cancers. RPN2, widely verified as an oncogene, encodes a protein that... (Review)
Review
Oncogenes together with tumor suppresser genes are confirmed to regulate tumor phenotype in human cancers. RPN2, widely verified as an oncogene, encodes a protein that is part of an N-oligosaccharyl transferase, and is observed to be aberrantly expressed in human malignancies. Accumulating evidence unveils the vital functions of RPN2, contributing to tumorigenicity, metastasis, progression, and multi-drug resistance. Furthermore, previous studies partly indicated that RPN2 was involved in tumor progression via contributing to N-glycosylation and regulating multiple signaling pathways. In addition, RPN2 was also confirmed as a downstream target involved in tumor progression. Moreover, with demonstrated prognosis value and therapeutic target, RPN2 was also determined as a promising biomarker for forecasting patients' prognostic and therapy efficacy. In the present review, we aimed to summarize the present studies of RPN2 in cancer, and enhance the understanding of RPN2's extensive functions and clinical significances.
Topics: Humans; Cell Line, Tumor; Drug Resistance, Multiple; Signal Transduction; Neoplasms; Hexosyltransferases; Proteasome Endopeptidase Complex
PubMed: 36621657
DOI: 10.1016/j.gene.2023.147168 -
Journal of Hepatology Nov 2016Antimicrobial resistance has become a major global public health security problem that needs coordinated approaches at regional, national and international levels.... (Review)
Review
Antimicrobial resistance has become a major global public health security problem that needs coordinated approaches at regional, national and international levels. Antibiotic overuse and the failure of control measures to prevent the spread of resistant bacteria in the healthcare environment have led to an alarming increase in the number of infections caused by resistant bacteria, organisms that resist many (multi-drug and extensively drug-resistant strains), if not all (pan-drug-resistant bacteria) currently available antibiotics. While Gram-positive cocci resistance (methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci) shows a heterogeneous geographical distribution, extended-spectrum β-lactamase-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae have become pandemic worldwide and endemic in some parts of the world, respectively. Moreover, currently available therapeutic options for resistant bacteria are very limited, with very few new agents in development. Antimicrobial resistance is especially relevant in decompensated cirrhosis. Firstly, cirrhotic patients are highly susceptible to develop infections caused by resistant bacteria as risk factors of multiresistance concentrate in this population (mainly repeated hospitalizations and antibiotic exposure). Secondly, inappropriate empirical antibiotic schedules easily translate into increased morbidity (acute kidney injury, acute-on-chronic liver failure, septic shock) and hospital mortality in advanced cirrhosis. Therefore, hepatologists must face nowadays a complex clinical scenario that requires new empirical antibiotic strategies that may further spread resistance. Global, regional and local preventive measures should therefore be implemented to combat antimicrobial resistance in cirrhosis including the restriction of antibiotic prophylaxis to high-risk populations, investigation on non-antibiotic prophylaxis, stewardship programs on adequate antibiotic prescription and on increasing awareness of the problem among health professionals, and well-defined early de-escalation policies based on rapid microbiological diagnostic tests. Other infection control practices such as hand hygiene and barrier precautions are also important. Clinical impact and cost-effectiveness of epidemiological surveillance programs (periodic rectal and nasal swabs) should also be explored.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gastroenterology; Humans; Infection Control; Methicillin-Resistant Staphylococcus aureus
PubMed: 27544545
DOI: 10.1016/j.jhep.2016.08.006 -
Life Sciences Dec 2020Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and... (Review)
Review
Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance.
Topics: Antineoplastic Agents; Cell Plasticity; Disease Progression; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Sarcoma; Tumor Microenvironment
PubMed: 33069737
DOI: 10.1016/j.lfs.2020.118589