-
Infectious Disease Clinics of North... Dec 2020
Topics: Animals; Anti-Infective Agents; Bacteria; Centers for Disease Control and Prevention, U.S.; Drug Resistance, Multiple, Bacterial; Drug Resistance, Multiple, Fungal; Fungi; Humans; United States
PubMed: 33131576
DOI: 10.1016/j.idc.2020.09.001 -
Current Topics in Medicinal Chemistry 2023Multi-drug resistance and its transmission is a ubiquitous health issue worldwide. The beta-lactamase AmpC resistance is a major concern among all health settings like... (Review)
Review
Multi-drug resistance and its transmission is a ubiquitous health issue worldwide. The beta-lactamase AmpC resistance is a major concern among all health settings like hospitals and child care centers, . The clinical pipeline of the new antibiotics remains dry due to the production of AmpC beta-lactamases by the bacteria to develop resistance against antibiotics. According to the global antimicrobial resistance and use surveillance system, the rate of resistance to ciprofloxacin an antibiotic commonly used to treat urinary tract infections, varied from 8.4% to 92.9% for and from 4.1% to 79.4% for in different countries. The lack of comprehensiveness within the data makes a choice problematic for the selection of appropriate β-lactam antibiotic for the treatment of resistant microorganisms. Most experts agree it is prudent to avoid expanded-spectrum ( third-generation) cephalosporins for the treatment of organisms posing the greatest risk of AmpC induction. Nonetheless, the development of specific inhibitors for the AmpC enzyme, either naturally or synthetically, is only unfolding. To date, there is no single and clinically active drug available that inhibits the AmpC enzyme and combats multidrug resistance and its transmission in individuals. The deficit of the enzyme inhibitor focused the researchers to work in the area. This present review will emphasize on the chemistry, and structure of clinically important and potent inhibitors against AmpC enzymes.
Topics: Humans; Anti-Bacterial Agents; beta-Lactamases; Bacterial Proteins; Escherichia coli; Cephalosporins; Drug Resistance, Multiple; Enzyme Inhibitors; Microbial Sensitivity Tests
PubMed: 37150991
DOI: 10.2174/1568026623666230504095005 -
Microbial Drug Resistance (Larchmont,... Jan 2020Tuberculosis (TB) is a major issue in global health and affects millions of people each year. Multidrug-resistant tuberculosis (MDR-TB) annually causes many deaths... (Review)
Review
Tuberculosis (TB) is a major issue in global health and affects millions of people each year. Multidrug-resistant tuberculosis (MDR-TB) annually causes many deaths worldwide. Development of a way to diagnose and treat patients with MDR-TB can potentially reduce the incidence of the disease. The current study reviews the risk factors, pattern of progression, mechanism of resistance, and interaction between bacteria and the host immune system, which disrupts the immune response. It also targets the components of (Mtb) and diagnosis and treatment options that could be available for clinical use in the near future. Mutations play an important role in development of MDR-TB and the selection of appropriate mutations can help to understand the type of resistance in patients to anti-TB drugs. In this way, they can be initially treated with proper and effective therapeutic choices, which can accelerate the course of treatment and improve patient health. Targeting the components and enzymes of Mtb is necessary for understanding bacterial survival and finding a way to destroy the pathogen and allow patients to recover faster and prevent the spread of disease, especially resistant strains.
Topics: Animals; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Global Health; Humans; Mutation; Mycobacterium tuberculosis; Risk Factors; Tuberculosis, Multidrug-Resistant
PubMed: 31517569
DOI: 10.1089/mdr.2018.0353 -
Toxins May 2023is a spore-forming, Gram-positive anaerobic pathogen that causes several disorders in humans and animals. A multidrug-resistant strain was isolated from the fecal...
is a spore-forming, Gram-positive anaerobic pathogen that causes several disorders in humans and animals. A multidrug-resistant strain was isolated from the fecal sample of a patient who was clinically suspected of gastrointestinal infection and had a recent history of antibiotic exposure and diarrhea. The strain was identified by 16s rRNA sequencing as . The strain's pathogenesis was analyzed through its complete genome, specifically antimicrobial resistance-related genes. The IRMC2505A genome contains 19 (, , , , , , , , , , , , , , , , , and ) antibiotic-susceptible genetic species according to the k-mer-based detection of antimicrobial resistance genes. Genome mapping using CARD and VFDB databases revealed significant (-value = 1 × 10) genes with aligned reads against antibiotic-resistant genes or virulence factors, including phospholipase C, perfringolysin O, collagenase, hyaluronidase, alpha-clostripain, exo-alpha-sialidase, and sialidase activity. In conclusion, this is the first report on from Saudi Arabia that conducted whole genome sequencing of IRMC2505A and confirmed the strain as an MDR bacterium with several virulence factors. Developing control strategies requires a detailed understanding of the epidemiology of , its virulence factors, and regional antimicrobial resistance patterns.
Topics: Animals; Humans; Clostridium perfringens; Virulence Factors; RNA, Ribosomal, 16S; Genomics; Anti-Bacterial Agents; Drug Resistance, Multiple; Clostridium Infections
PubMed: 37368661
DOI: 10.3390/toxins15060359 -
ACS Infectious Diseases Nov 2023Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One... (Review)
Review
Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is . The extensive and inappropriate treatments for infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in . Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in . Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system's differential expression and positional mutation in may provide insight into developing strategic therapies for one health application.
Topics: Membrane Proteins; Membrane Transport Proteins; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Salmonella
PubMed: 37910638
DOI: 10.1021/acsinfecdis.3c00408 -
Frontiers in Cellular and Infection... 2022Emerging antibiotic resistance in bacteria endorses the failure of existing drugs with chronic illness, complicated treatment, and ever-increasing expenditures. Bacteria... (Review)
Review
Emerging antibiotic resistance in bacteria endorses the failure of existing drugs with chronic illness, complicated treatment, and ever-increasing expenditures. Bacteria acquire the nature to adapt to starving conditions, abiotic stress, antibiotics, and our immune defense mechanism due to its swift evolution. The intense and inappropriate use of antibiotics has led to the development of multidrug-resistant (MDR) strains of bacteria. Phytochemicals can be used as an alternative for complementing antibiotics due to their variation in metabolic, genetic, and physiological fronts as well as the rapid evolution of resistant microbes and lack of tactile management. Several phytochemicals from diverse groups, including alkaloids, phenols, coumarins, and terpenes, have effectively proved their inhibitory potential against MDR pathogens through their counter-action towards bacterial membrane proteins, efflux pumps, biofilms, and bacterial cell-to-cell communications, which are important factors in promoting the emergence of drug resistance. Plant extracts consist of a complex assortment of phytochemical elements, against which the development of bacterial resistance is quite deliberate. This review emphasizes the antibiotic resistance mechanisms of bacteria, the reversal mechanism of antibiotic resistance by phytochemicals, the bioactive potential of phytochemicals against MDR, and the scientific evidence on molecular, biochemical, and clinical aspects to treat bacterial pathogenesis in humans. Moreover, clinical efficacy, trial, safety, toxicity, and affordability investigations, current status and developments, related demands, and future prospects are also highlighted.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Biofilms; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Phytochemicals
PubMed: 35846771
DOI: 10.3389/fcimb.2022.883839 -
Archives of Microbiology Mar 2023Infections by ESKAPE (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens... (Review)
Review
Infections by ESKAPE (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens cause major concern due to their multi-drug resistance (MDR). The ESKAPE pathogens are frequently linked to greater mortality, diseases, and economic burden in healthcare worldwide. Therefore, the use of plants as a natural source of antimicrobial agents provide a solution as they are easily available and safe to use. These natural drugs can also be enhanced by incorporating silver nanoparticles and combining them with existing antibiotics. By focussing the attention on the ESKAPE organisms, the MDR issue can be addressed much better.
Topics: Drug Resistance, Multiple, Bacterial; Humans; Plants; Anti-Bacterial Agents; Metal Nanoparticles; Silver; Plant Extracts; Gram-Positive Bacteria; Gram-Negative Bacteria; Cross Infection
PubMed: 36917278
DOI: 10.1007/s00203-023-03455-6 -
Molecular Biology Reports Aug 2021Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug... (Review)
Review
BACKGROUND
Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs).
METHODS AND RESULTS
This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease.
CONCLUSIONS
LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.
Topics: Biomarkers, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; RNA, Long Noncoding
PubMed: 34333735
DOI: 10.1007/s11033-021-06603-7 -
International Journal of Pharmaceutics Aug 2022Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the...
Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the major cause of MDR. Herein, a linear polyethylene glycol (PEI) conjugated with dicyandiamide, which called polymeric metformin (PolyMet), was successfully synthesized as a simple and biocompatible polymer of metformin. PolyMet showed the potential to reverse MDR by inhibiting the efflux of the substrate of ATP-binding cassette (ABC) transporter from DOX resistant MCF-7 cells (MCF-7/DOX). To test its MDR reversing effect, PolyMet was combined with DOX to treat mice carrying MCF-7/DOX xenografts. In order to decrease the toxicities of DOX and delivery PolyMet and DOX to tumor at the same time, PolyMet was complexed with poly-γ-glutamic acid-doxorubicin (PGA-DOX) electrostatically at the optimal ratio of 2:3, which were further coated with lipid membrane to form lipid/PolyMet-(PGA-DOX) nanoparticles (LPPD). The particle size of LPPD was 165.8 nm, and the zeta potential was +36.5 mV. LPPD exhibited favorable cytotoxicity and cellular uptake in MCF-7/DOX. Meanwhile, the bioluminescence imaging and immunohistochemical analysis indicated that LPPD effectively conquered DOX-associated MDR by blocking ABC transporters (ABCB1 and ABCC1) via PolyMet. Remarkably, LPPD significantly inhibited the tumor growth and lowered the systemic toxicity in a murine MCF-7/DOX tumor model. This is the first time to reveal that PolyMet can enhance the anti-tumor efficacy of DOX by dampening ABC transporters and activating the AMPK/mTOR pathway, which is a promising strategy for drug-resistant breast cancer therapy.
Topics: Animals; Female; Humans; Mice; Adenosine Triphosphate; ATP-Binding Cassette Transporters; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; MCF-7 Cells; Metformin; Polyethylene Glycols
PubMed: 35750278
DOI: 10.1016/j.ijpharm.2022.121931 -
Medicina Intensiva Sep 2022Pseudomonas aeruginosa is the microorganism most frequently involved in the main ICU-acquired infections, with special importance in ventilator associated pneumonia. Its... (Review)
Review
Pseudomonas aeruginosa is the microorganism most frequently involved in the main ICU-acquired infections, with special importance in ventilator associated pneumonia. Its importance lies, in addition to its high incidence in critically ill patients, in the severity of the infections it causes and in the difficulty of its antimicrobial treatment, directly related to the high percentage of resistance to antibiotics classically considered first-line. New active antibiotics have recently been developed against Pseudomonas aeruginosa, even against multi-drug resistant strains. This review analyzes both the differential characteristics of Pseudomonas aeruginosa infections and the new therapeutic options, focusing on multi-drug resistant Pseudomonas aeruginosa.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 35840495
DOI: 10.1016/j.medine.2022.06.014