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Nature Structural & Molecular Biology Sep 2023The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete....
The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures of 17 distinct compounds from six different antibiotic classes bound to the bacterial ribosome at resolutions ranging from 1.6 to 2.2 Å. The improved resolution enables a precise description of antibiotic-ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between the drugs and their target. Our results reveal a high structural conservation in the binding mode between antibiotics with the same scaffold, including ordered water molecules. Water molecules are visualized within the antibiotic binding sites that are preordered, become ordered in the presence of the drug and that are physically displaced on drug binding. Insight into RNA-ligand interactions will facilitate development of new antimicrobial agents, as well as other RNA-targeting therapies.
Topics: Anti-Bacterial Agents; Ribosomes; Bacteria; Binding Sites; RNA
PubMed: 37550453
DOI: 10.1038/s41594-023-01047-y -
Bioorganic & Medicinal Chemistry Letters May 2023The success of precision medicine coupled with the disappointing impact of broad-spectrum antibiotic use on microbiome stability and bacterial resistance, has triggered... (Review)
Review
The success of precision medicine coupled with the disappointing impact of broad-spectrum antibiotic use on microbiome stability and bacterial resistance, has triggered a shift in antibiotic design strategies toward precision antibiotics. This also includes the implementation of novel vectorization approaches directed to improve the internalization of antibacterial agents into deadly gram-negative pathogens through precise and well-defined mechanisms. The conjugation of antibiotics to siderophores (iron scavengers), which are compounds that are able to afford stable iron-complexes that facilitate the internalization into the cell by using bacterial iron uptake pathways as gateways, is a strategy that has begun to show excellent results with the commercialization of the first antibiotic based on this principle, cefiderocol. This digests review provides an overview of the molecular basis for this antibiotic-siderophore conjugation approach, along with recent successful examples and highlights future challenges facing this booming research area.
Topics: Humans; Anti-Bacterial Agents; Siderophores; Iron; Bacterial Infections
PubMed: 37031730
DOI: 10.1016/j.bmcl.2023.129282 -
Frontiers in Bioscience (Elite Edition) Jul 2023Infection diagnosis and antibiotic sensitivity testing are important aspects of clinical microbiology that are in dire need of improvement owing to the inadequate... (Review)
Review
Infection diagnosis and antibiotic sensitivity testing are important aspects of clinical microbiology that are in dire need of improvement owing to the inadequate current standards in the early detection of bacterial response to antibiotics. The increasing antimicrobial resistance is a serious global threat to human health. Current resistance-detecting methods, using the phenotypic antibiotic sensitivity test, which measures bacterial growth as affected by antibiotics, have long analysis times. Therefore, new and rapid methods are needed to detect antibiotic resistance. Here, we review the methods used to detect antibiotic resistance in bacteria, including that caused by biofilm development, and we look at the development of rapid methods for evaluating antimicrobial resistance (AMR).
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Biofilms
PubMed: 37743230
DOI: 10.31083/j.fbe1503019 -
The Medical Journal of Malaysia Sep 2021Antibiotic resistance is a burgeoning problem worldwide. The trend of bacterial resistance has increased over the past decade in which more common bacteria are becoming... (Review)
Review
INTRODUCTION
Antibiotic resistance is a burgeoning problem worldwide. The trend of bacterial resistance has increased over the past decade in which more common bacteria are becoming resistant to almost all the antibiotics currently in use, posing a threat to humans and even livestock.
METHODS
The databases used to search for the relevant articles for this review include PubMed, Science Direct, and Scopus. The following keywords were used in the search: Antimicrobial resistance, Malaysian action plan, antibioticresistant bacteria, and Malaysian National Surveillance on Antimicrobial Resistance (NSAR). The relevant articles published in English were considered.
RESULTS
The antibiotic-resistant bacteria highlighted in this review showed an increase in resistance patterns to the majority of the antibiotics tested. The Malaysian government has come up with an action plan to create public awareness and to educate them regarding the health implications of antibiotic resistance.
CONCLUSION
Antimicrobial resistance in Malaysia continues to escalate and is attributed to the overuse and misuse of antibiotics in various fields. As this crisis impacts the health of both humans and animals, therefore a joined continuous effort from all sectors is warranted to reduce the spread and minimize its development.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Malaysia
PubMed: 34508377
DOI: No ID Found -
Advanced Drug Delivery Reviews Mar 2018Despite the wide success of antibiotics in modern medicine, the treatment of bacterial infections still faces critical challenges, especially due to the rapid emergence... (Review)
Review
Despite the wide success of antibiotics in modern medicine, the treatment of bacterial infections still faces critical challenges, especially due to the rapid emergence of antibiotic resistance. As a result, local antimicrobial treatment aimed at enhancing drug concentration at the site of infection while avoiding systemic exposure is becoming increasingly attractive, as it may alleviate resistance development. Meanwhile, therapeutic nanoparticles, especially liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles, are gaining traction to improve the therapeutic efficacy with many applications specifically focused on local antimicrobial treatment. This review highlights topics where nanoparticle-based strategies hold significant potential to advance treatment against local bacterial infections, including (1) promoting antibiotic localization to the pathogen, (2) modulating drug-pathogen interaction against antibiotic resistance, and (3) enabling novel anti-virulence approaches for 'drug-free' antimicrobial activity. In each area, we highlight the innovative antimicrobial strategies tailored for local applications and review the progress made for the treatment of bacterial infections.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Delivery Systems; Humans; Nanoparticles
PubMed: 28939377
DOI: 10.1016/j.addr.2017.09.015 -
International Journal of Environmental... Aug 2014Although pregnancy is considered as a physiological state, most pregnant women in developed countries receive multiple medications to prevent maternal or neonatal... (Review)
Review
Although pregnancy is considered as a physiological state, most pregnant women in developed countries receive multiple medications to prevent maternal or neonatal complications, with antibiotics among the most frequently prescribed. During pregnancy, antibiotics are often prescribed in the context of preterm labor, intrapartum fever, prevention of neonatal Group B Streptococcus fever, and cesarean section. Outside this period, they are commonly prescribed in the community setting for respiratory, urinary, and ear, nose and throat infection symptoms. Whereas some of the current indications have insightful reasons to justify their use, potential risks related to overuse and misuse may surpass the benefits. Of note, the recent 2014 World Health Assembly expressed serious concern regarding antibiotic resistance due to antibiotic overuse and misuse and urged immediate action to combat antibiotic resistance on a global scale. Most studies in the obstetrics field have focused on the benefits of antibiotics for short-term maternal and neonatal complications, but with very little (if any) interest in long-term consequences.
Topics: Anti-Bacterial Agents; Female; Humans; Pregnancy; Risk Assessment
PubMed: 25105549
DOI: 10.3390/ijerph110807993 -
Microbes and Infection Jun 2022Pseudomonas aeruginosa is an opportunistic pathogen responsible for acute hospital-acquired infections. This review described various therapeutic approaches to treat... (Review)
Review
Pseudomonas aeruginosa is an opportunistic pathogen responsible for acute hospital-acquired infections. This review described various therapeutic approaches to treat infections caused by P. aeruginosa, including conventional therapy, novel antibiotic treatments and treatments other than antibiotics. Most of the developments are still in research that will provide novel treatment options in future.
Topics: Anti-Bacterial Agents; Humans; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 35139390
DOI: 10.1016/j.micinf.2022.104950 -
Molecules (Basel, Switzerland) Sep 2019Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a... (Review)
Review
Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a glimmer of hope in a currently limited pipeline of new antibiotics. One strategy involves conjugating iron-chelating microbial siderophores to an antibiotic or antimicrobial agent to enhance uptake and antibacterial potency. Cefiderocol (S-649266) is a promising cephalosporin-catechol conjugate currently in phase III clinical trials that utilizes iron-mediated active transport and demonstrates enhanced potency against multi-drug resistant (MDR) Gram-negative pathogens. Such molecules demonstrate that siderophore-antibiotic conjugates could be important future medicines to add to our antibiotic arsenal. This review is written in the context of the chemical design of siderophore-antibiotic conjugates focusing on the differing siderophore, linker, and antibiotic components that make up conjugates. We selected chemically distinct siderophore-antibiotic conjugates as exemplary conjugates, rather than multiple analogues, to highlight findings to date. The review should offer a general guide to the uninitiated in the molecular design of siderophore-antibiotic conjugates.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Design; Ferrous Compounds; Humans; Peptides; Siderophores
PubMed: 31514464
DOI: 10.3390/molecules24183314 -
Environment International Mar 2019Antibiotic is one of the most significant discoveries and have brought a revolution in the field of medicine for human therapy. In addition to the medical uses,... (Review)
Review
Antibiotic is one of the most significant discoveries and have brought a revolution in the field of medicine for human therapy. In addition to the medical uses, antibiotics have broad applications in agriculture and animal husbandry. In developing nations, antibiotics use have helped to increase the life expectancy by lowering the deaths due to bacterial infections, but the risks associated with antibiotics pollution is largely affecting people. Since antibiotics are released partially degraded and undegraded into environment creating antibiotic pollution, and its bioremediation is a challenging task. In the present review, we have discussed the primary antibiotic sources like hospitals, dairy, and agriculture causing antibiotic pollution and their innovative detection methods. The strong commitment towards the resistance prevention and participation, nations through strict policies and their implementations now come to fight against the antibiotic resistance under WHO. The review also deciphers the bacterial evolution based strategies to overcome the effects of antibiotics, so the antibiotic degradation and elimination from the environment and its health benefits. The present review focuses on the environmental sources of antibiotics, it's possible degradation mechanisms, health effects, and bacterial antibiotics resistance mechanisms.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Biodegradation, Environmental; Drug Resistance, Bacterial; Environmental Pollutants; Humans
PubMed: 30684803
DOI: 10.1016/j.envint.2018.12.065 -
Military Medical Research Jan 2024Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens... (Review)
Review
Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO's report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.
Topics: Humans; Artificial Intelligence; Anti-Bacterial Agents; Drug Resistance, Bacterial; Public Health
PubMed: 38254241
DOI: 10.1186/s40779-024-00510-1