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Frontiers in Cellular and Infection... 2017is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of... (Review)
Review
is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant , few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of is important. In this review, we summarize current studies on the virulence factors that contribute to pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant are summarized.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Biological Therapy; Drug Resistance, Multiple, Bacterial; Humans; Virulence Factors
PubMed: 28348979
DOI: 10.3389/fcimb.2017.00055 -
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 -
International Journal of Molecular... May 2020Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains... (Review)
Review
Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains the main method for cancer treatment. Depending on the mechanism of action, commonly used chemotherapeutic agents can be divided into several classes (antimetabolites, alkylating agents, mitotic spindle inhibitors, topoisomerase inhibitors, and others). Multidrug resistance (MDR) is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. The mechanisms of MDR include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations). Rapidly increasing numbers of biomedical studies are focused on designing chemotherapeutics that are able to evade or reverse MDR. The aim of this review is not only to demonstrate the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment but also to present the mechanisms of action of novel potential antitumor drugs which have been designed to overcome these resistance mechanisms. Better understanding of the mechanisms of MDR and targets of novel chemotherapy agents should provide guidance for future research concerning new effective strategies in cancer treatment.
Topics: Animals; Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Pharmacogenetics
PubMed: 32370233
DOI: 10.3390/ijms21093233 -
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 -
Microbial Pathogenesis Jul 2018In the current healthcare environment, an alarming rise in multi-drug resistant bacterial infections has led to a global health threat. The lack of new antibiotics has... (Review)
Review
BACKGROUND
In the current healthcare environment, an alarming rise in multi-drug resistant bacterial infections has led to a global health threat. The lack of new antibiotics has created a need for developing alternative strategies.
OBJECTIVE
Understanding the antibacterial mechanisms of cinnamon and its constituents is crucial to enhance it as a potential new source of antibiotic. The objective of this review is to provide a compilation of all described mechanisms of antibacterial action of cinnamon and its constituents and synergism with commercial antibiotics in order to better understand how cinnamon and its constituents can collaborate as alternative treatment to multi-drug resistant bacterial infections.
METHODS
The relevant references on antibacterial activities of cinnamon and its constituents were searched. Meanwhile, the references were classified according to the type of mechanism of action against bacteria. Relationships of cinnamon or its constituents and antibiotics were also analyzed and summarized.
RESULTS
Cinnamon extracts, essential oils, and their compounds have been reported to inhibit bacteria by damaging cell membrane; altering the lipid profile; inhibiting ATPases, cell division, membrane porins, motility, and biofilm formation; and via anti-quorum sensing effects.
CONCLUSION
This review describes the antibacterial effects of cinnamon and its constituents, such as cinnamaldehyde and cinnamic acid, against pathogenic Gram-positive and Gram-negative bacteria. The review also provides an overview of the current knowledge of the primary modes of action of these compounds as well as the synergistic interactions between cinnamon or its constituents with known antibacterial agents. This information will be useful in improving the effectiveness of therapeutics based on these compounds.
Topics: Acrolein; Adenosine Triphosphatases; Anti-Bacterial Agents; Bacteria; Biofilms; Cell Division; Cell Membrane; Cinnamates; Cinnamomum zeylanicum; Databases, Factual; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Oils, Volatile; Plant Extracts; Porins; Quorum Sensing
PubMed: 29702210
DOI: 10.1016/j.micpath.2018.04.036 -
Microbiological Research Jun 2021The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in... (Review)
Review
The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Biofilms; Cross Infection; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Host-Pathogen Interactions; Humans; Sepsis; Virulence Factors
PubMed: 33618061
DOI: 10.1016/j.micres.2021.126722 -
Frontiers in Cellular and Infection... 2018Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a... (Review)
Review
Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a revitalization of bacteriophage (phage) studies in the Western world. Phage therapy mainly utilizes obligately lytic phages to kill their respective bacterial hosts, while leaving human cells intact and reducing the broader impact on commensal bacteria that often results from antibiotic use. Phage therapy is rapidly evolving and has resulted in cases of life-saving therapeutic use and multiple clinical trials. However, one of the biggest challenges this antibiotic alternative faces relates to regulations and policy surrounding clinical use and implementation beyond compassionate cases. This review discusses the multi-drug resistant Gram-negative pathogens of highest critical priority and summarizes the current state-of-the-art in phage therapy targeting these organisms. It also examines phage therapy in humans in general and the approaches different countries have taken to introduce it into clinical practice and policy. We aim to highlight the rapidly advancing field of phage therapy and the challenges that lie ahead as the world shifts away from complete reliance on antibiotics.
Topics: Bacteriolysis; Bacteriophages; Clinical Trials as Topic; Drug Approval; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Phage Therapy
PubMed: 30406049
DOI: 10.3389/fcimb.2018.00376 -
Biochemical Society Transactions Oct 2015In most organisms, ABC transporters constitute one of the largest families of membrane proteins. In humans, their functions are diverse and underpin numerous key... (Review)
Review
In most organisms, ABC transporters constitute one of the largest families of membrane proteins. In humans, their functions are diverse and underpin numerous key physiological processes, as well as being causative factors in a number of clinically relevant pathologies. Advances in our understanding of these diseases have come about through combinations of genetic and protein biochemical investigations of these transporters and the power of in vitro and in vivo investigations is helping to develop genotype-phenotype understanding. However, the importance of ABC transporter research goes far beyond human biology; microbial ABC transporters are of great interest in terms of understanding virulence and drug resistance and industrial biotechnology researchers are exploring the potential of prokaryotic ABC exporters to increase the capacity of synthetic biology systems. Plant ABC transporters play important roles in transport of hormones, xenobiotics, metals and secondary metabolites, pathogen responses and numerous aspects of development, all of which are important in the global food security area. For 3 days in Chester, this Biochemical Society Focused Meeting brought together researchers with diverse experimental approaches and with different fundamental questions, all of which are linked by the commonality of ABC transporters.
Topics: ATP-Binding Cassette Transporters; Animals; Arabidopsis Proteins; Bacterial Proteins; Biological Transport; Biomedical Research; Drug Resistance, Multiple; Humans; Multigene Family; Species Specificity
PubMed: 26517919
DOI: 10.1042/BST20150139 -
BMC Infectious Diseases Jul 2021This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections... (Clinical Trial)
Clinical Trial
BACKGROUND
This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs.
METHODS
We conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI.
RESULTS
2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp., Pseudomonas spp., E. coli, and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli, and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015-2018, the mortality rate of gram-negative BSI remains unchanged at about 20% (p-value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively.
CONCLUSIONS
The emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.
Topics: Bacteremia; Bacteria; Combined Modality Therapy; Drug Resistance, Bacterial; Drug Resistance, Multiple; Female; Humans; Iran; Klebsiella pneumoniae; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Sepsis
PubMed: 34215207
DOI: 10.1186/s12879-021-06243-z -
Frontiers in Cellular and Infection... 2023Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and... (Review)
Review
Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and DR-TB, including prevalence, incidence, and mortality. We discuss the challenges in diagnosing TB and DR-TB in children and the limitations of current diagnostic tools. We summarize the challenges associated with treating multi-drug resistance TB in childhood, including limitations of current treatment options, drug adverse effects, prolonged regimens, and managing and monitoring during treatment. We highlight the urgent need for improved diagnosis and treatment of DR-TB in children. The treatment of children with multidrug-resistant tuberculosis will be expanded to include the evaluation of new drugs or new combinations of drugs. Basic research is needed to support the technological development of biomarkers to assess the phase of therapy, as well as the urgent need for improved diagnostic and treatment options.
Topics: Child; Humans; Antitubercular Agents; Tuberculosis; Tuberculosis, Multidrug-Resistant; Prevalence; Drug Resistance, Multiple; Mycobacterium tuberculosis
PubMed: 37333849
DOI: 10.3389/fcimb.2023.1183590