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Annals of Palliative Medicine Jun 2021The prevalence of antibiotic resistance is a growing worldwide problem in the control of pathogens, particularly negative bacteria that are resistant to antibiotics,... (Review)
Review
The prevalence of antibiotic resistance is a growing worldwide problem in the control of pathogens, particularly negative bacteria that are resistant to antibiotics, Pseudomonas aeruginosa (PA) is one of these bacteria. The development of new effective antibiotics is time-consuming and costly, and the new antibiotics may become resistant again. Therefore, non-antibiotic clinical treatment for antibiotic-resistant PA infection is necessary and needs to be strengthened. The antibiotic resistance (AR) mechanism of PA is complex. Biofilm formation is one of the reasons why its resistance is difficult to overcome. The formation of biofilms is mainly regulated by quorum sensing (QS). QS is a mechanism by which PA increases its virulence by producing small diffusible molecules, which regulates a series of genes associated with virulence and nutrient acquisition. QS inhibitors are potions that obstruct QS systems in bacteria and destruction of virulence. This review summarizes AR mechanism of PA, Basic knowledge of QS of PA and some non-antibiotic methods for inhibiting PA, including QS inhibitors, which have potential and far-reaching significance for antibiotic-resistant PA's clinical treatment. The review helps to provide new ideas and new schemes for clinical anti-PA infection research and treatment, and has positive significance for delaying the occurrence of bacterial drug resistance and antibiotic use management.
Topics: Anti-Bacterial Agents; Biofilms; Humans; Pseudomonas aeruginosa; Quorum Sensing; Virulence Factors
PubMed: 34044573
DOI: 10.21037/apm-20-2247 -
Current Microbiology Sep 2022An increasing number of bacterial pathogens are acquiring resistance to the commonly used antibiotics. This has spurred a global threat leading to a resistance era and... (Review)
Review
An increasing number of bacterial pathogens are acquiring resistance to the commonly used antibiotics. This has spurred a global threat leading to a resistance era and has penetrated the consciousness of the common people and the clinicians alike. The delay in discovering new antibiotics has exacerbated the resistance problem, forcing researchers to focus on unconventional antimicrobial therapeutics that differ from conventional antibiotics. Alternative therapies have emerged in recent years, including antimicrobial peptides, phage therapy, efflux pump inhibitors, antibodies, and immunomodulatory agents, which have produced impressive results in both laboratory and in clinical trials. Additionally, ultra-narrow-spectrum therapeutics such as CRISPR-Cas system and peptide nucleic acids aided in the development of sequence-specific antimicrobials. Moreover, combinatorial therapies that combine these new approaches have been efficient enough to get approval for clinical use and have accelerated the discovery of novel combination approaches that enhance the performance of already in-use antibiotics. In this review, we provide an overview of these approaches along with studies that focus on the uncharted microbial territories that have been able to deliver some of the important new antibiotics of recent times. It is hoped that the information gathered in this article will provide an update on the current antibiotic resistance threat and encourage profound research.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Drug Resistance, Microbial; Humans; Peptide Nucleic Acids
PubMed: 36155858
DOI: 10.1007/s00284-022-03029-7 -
Nature Chemical Biology Mar 2015Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a... (Review)
Review
Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. Also important, however, is the fact that a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming and interpopulation interactions. These strategies can enable rapid population recovery after antibiotic treatment and provide a time window during which otherwise susceptible bacteria can acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans
PubMed: 25689336
DOI: 10.1038/nchembio.1754 -
British Journal of Pharmacology Sep 2017Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a... (Review)
Review
Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases.
Topics: Anti-Bacterial Agents; Bacteria; Communicable Diseases; Humans; Macrolides
PubMed: 28664582
DOI: 10.1111/bph.13936 -
Journal of Food and Drug Analysis Mar 2023Owing to the widespread emergence and proliferation of antibiotic-resistant bacteria, the therapeutic benefits of antibiotics have been reduced. In addition, the ongoing... (Review)
Review
Owing to the widespread emergence and proliferation of antibiotic-resistant bacteria, the therapeutic benefits of antibiotics have been reduced. In addition, the ongoing evolution of multidrug-resistant pathogens poses a challenge for the scientific community to develop sensitive analytical methods and innovative antimicrobial agents for the detection and treatment of drug-resistant bacterial infections. In this review, we have described the antibiotic resistance mechanisms that occur in bacteria and summarized the recent developments in detection strategies for monitoring drug resistance using different diagnostic methods in three aspects, including electrostatic attraction, chemical reaction, and probe-free analysis. Additionally, to understand the effective inhibition of drug-resistant bacterial growth by recent nano-antibiotics, the underlying antimicrobial mechanisms and efficacy of biogenic silver nanoparticles and antimicrobial peptides, which have shown promise, and the rationale, design, and potential improvements to these methods are also highlighted in this review. Finally, the primary challenges and future trends in the rational design of facile sensing platforms and novel antibacterial agents against superbugs are discussed.
Topics: Metal Nanoparticles; Silver; Bacteria; Anti-Bacterial Agents
PubMed: 37224551
DOI: 10.38212/2224-6614.3433 -
Journal of Infection and Public Health Apr 2023Antibiotics help in preventing and treating infections and increasing life expectancy globally. Globally, many people's lives are being threatened by the emergence of... (Review)
Review
Antibiotics help in preventing and treating infections and increasing life expectancy globally. Globally, many people's lives are being threatened by the emergence of antimicrobial resistance (AMR). The cost of treating and preventing infectious diseases has increased due to AMR. Bacteria can resist the effects of antibiotics by altering drug targets, inactivating drugs, and activating drug efflux pumps. According to estimates, five million individuals died in 2019 from AMR-related causes, wherein 1.3 million deaths were directly linked to bacterial AMR. Sub-Saharan Africa (SSA) experienced the greatest mortality rate from AMR in 2019. In this article, we discuss AMR's causes and challenges SSA faces in implementing AMR prevention measures and propose recommendations to address the challenges. Antibiotic misuse and overuse, widespread usage in agriculture, and the pharmaceutical industry's absence of new antibiotic development are the factors contributing to AMR. SSA's challenges in preventing AMR include poor AMR surveillance and lack of collaboration, irrational use of antibiotics, weak medicine regulatory systems, lack of infrastructural and institutional capacities, lack of human resources, and inefficient infection prevention and control (IPC) practices. The challenges faced by countries in SSA can be addressed by increasing the public's knowledge of antibiotics and AMR, promoting antibiotic stewardship, improving AMR surveillance, promoting collaboration within and beyond countries, antibiotics regulatory enforcement, and improving the practice of IPC measures at home, food handling establishments, and healthcare facilities.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Bacterial Infections; Bacteria; Antimicrobial Stewardship
PubMed: 36870230
DOI: 10.1016/j.jiph.2023.02.020 -
Advances in Microbial Physiology 2023Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to... (Review)
Review
Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to resist killing or growth inhibition by antibiotics and the ways in which bacteria share these traits with one another. This work has led to the advancement of new drugs, combination therapy regimens, and a deeper appreciation for the adaptability seen in microorganisms. However, while the primary mechanisms of action of most antibiotics are well understood, the more subtle contributions of bacterial metabolic state to repairing or preventing damage caused by antimicrobials (thereby promoting survival) are still understudied. Here, we review a modern viewpoint on a classical system: examining bacterial metabolism's connection to antibiotic susceptibility. We dive into the relationship between metabolism and antibiotic efficacy through the lens of growth rate, energy state, resource allocation, and the infection environment, focusing on cell wall-active antibiotics.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Anti-Infective Agents; Bacterial Infections; Cell Wall
PubMed: 37507159
DOI: 10.1016/bs.ampbs.2023.04.002 -
Infection and Immunity Aug 2023The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation...
The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge. Bacteriophages have evolved to prey on these biofilms over millions of years, using hydrolases and depolymerases to penetrate biofilms and reach cellular targets. Here, we assessed how a newly discovered KMV-like phage (ΦJB10) interacts with antibiotics to treat P. aeruginosa more effectively in both planktonic and biofilm forms. By testing representatives of four classes of antibiotics (cephalosporins, aminoglycosides, fluoroquinolones, and carbapenems), we demonstrated class-dependent interactions between ΦJB10 and antibiotics in both biofilm clearance and P. aeruginosa killing. Despite identifying antagonism between some antibiotic classes and ΦJB10 at early time points, all classes showed neutral to favorable interactions with the phage at later time points. In one notable example where the antibiotic alone had poor activity against both biofilm and high-density planktonic cells, we found that addition of ΦJB10 demonstrated synergy and resulted in effective treatment of both. Further, ΦJB10 seemed to act as an adjuvant to several antibiotics, reducing the concentration of antibiotics required to ablate the biofilm. This report shows that phages such as ΦJB10 may be valuable additions to the armamentarium against difficult-to-treat biofilm-based infections.
Topics: Humans; Anti-Bacterial Agents; Pseudomonas Phages; Pseudomonas Infections; Bacteriophages; Cephalosporins; Biofilms; Pseudomonas aeruginosa
PubMed: 37404162
DOI: 10.1128/iai.00065-23 -
Marine Drugs Oct 2023In the post-antibiotic era, the rapid development of antibiotic resistance and the shortage of available antibiotics are triggering a new health-care crisis. The... (Review)
Review
In the post-antibiotic era, the rapid development of antibiotic resistance and the shortage of available antibiotics are triggering a new health-care crisis. The discovery of novel and potent antibiotics to extend the antibiotic pipeline is urgent. Small-molecule antimicrobial peptides have a wide variety of antimicrobial spectra and multiple innovative antimicrobial mechanisms due to their rich structural diversity. Consequently, they have become a new research hotspot and are considered to be promising candidates for next-generation antibiotics. Therefore, we have compiled a collection of small-molecule antimicrobial peptides derived from marine microorganisms from the last fifteen years to show the recent advances in this field. We categorize these compounds into three classes-cyclic oligopeptides, cyclic depsipeptides, and cyclic lipopeptides-according to their structural features, and present their sources, structures, and antimicrobial spectrums, with a discussion of the structure activity relationships and mechanisms of action of some compounds.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Oligopeptides; Depsipeptides; Antimicrobial Peptides
PubMed: 37888482
DOI: 10.3390/md21100547 -
Biochimica Et Biophysica Acta.... Jan 2024Antibiotic resistance has led to an increase in the number of patient hospitalizations and deaths. The situation for gram-negative bacteria is especially dire as the... (Review)
Review
Antibiotic resistance has led to an increase in the number of patient hospitalizations and deaths. The situation for gram-negative bacteria is especially dire as the last new class of antibiotics active against these bacteria was introduced to the clinic over 60 years ago, thus there is an immediate unmet need for new antibiotic classes able to overcome resistance. The outer membrane, a unique and essential structure in gram-negative bacteria, contains multiple potential antibacterial targets including BamA, an outer membrane protein that folds and inserts transmembrane β-barrel proteins. BamA is essential and conserved, and its outer membrane location eliminates a barrier that molecules must overcome to access this target. Recently, antibacterial small molecules, natural products, peptides, and antibodies that inhibit BamA activity have been reported, validating the druggability of this target and generating potential leads for antibiotic development. This review will describe these BamA inhibitors, highlight their key attributes, and identify challenges with this potential target.
Topics: Humans; Escherichia coli Proteins; Escherichia coli; Protein Folding; Bacterial Outer Membrane Proteins; Gram-Negative Bacteria; Anti-Bacterial Agents
PubMed: 37852326
DOI: 10.1016/j.bbamcr.2023.119609