Antibacterial potential of hGlyrichin encoded by a human gene. - Related Documents




#
Rank
Similarity
Title + Abs.
Year
PMID
012345
905601.0000Antibacterial potential of hGlyrichin encoded by a human gene. Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero-immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42-60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero-immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide.201222083756
910210.9992An Organogold Compound as Potential Antimicrobial Agent against Drug-Resistant Bacteria: Initial Mechanistic Insights. The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.202134181818
910320.9991Development of cannabidiol derivatives as potent broad-spectrum antibacterial agents with membrane-disruptive mechanism. The emergence of antibiotic resistance has brought a significant burden to public health. Here, we designed and synthesized a series of cannabidiol derivatives by biomimicking the structure and function of cationic antibacterial peptides. This is the first report on the design of cannabidiol derivatives as broad-spectrum antibacterial agents. Through the structure-activity relationship (SAR) study, we found a lead compound 23 that killed both Gram-negative and Gram-positive bacteria via a membrane-targeting mechanism of action with low resistance frequencies. Compound 23 also exhibited very weak hemolytic activity, low toxicity toward mammalian cells, and rapid bactericidal properties. To further validate the membrane action mechanism of compound 23, we performed transcriptomic analysis using RNA-seq, which revealed that treatment with compound 23 altered many cell wall/membrane/envelope biogenesis-related genes in Gram-positive and Gram-negative bacteria. More importantly, compound 23 showed potent in vivo antibacterial efficacy in murine corneal infection models caused by Staphylococcus aureus or Pseudomonas aeruginosa. These findings would provide a new design idea for the discovery of novel broad-spectrum antibacterial agents to overcome the antibiotic resistance crisis.202438266554
424630.9991Bacteriocins to Thwart Bacterial Resistance in Gram Negative Bacteria. An overuse of antibiotics both in human and animal health and as growth promoters in farming practices has increased the prevalence of antibiotic resistance in bacteria. Antibiotic resistant and multi-resistant bacteria are now considered a major and increasing threat by national health agencies, making the need for novel strategies to fight bugs and super bugs a first priority. In particular, Gram-negative bacteria are responsible for a high proportion of nosocomial infections attributable for a large part to Enterobacteriaceae, such as pathogenic Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. To cope with their highly competitive environments, bacteria have evolved various adaptive strategies, among which the production of narrow spectrum antimicrobial peptides called bacteriocins and specifically microcins in Gram-negative bacteria. They are produced as precursor peptides that further undergo proteolytic cleavage and in many cases more or less complex posttranslational modifications, which contribute to improve their stability and efficiency. Many have a high stability in the gastrointestinal tract where they can target a single pathogen whilst only slightly perturbing the gut microbiota. Several microcins and antibiotics can bind to similar bacterial receptors and use similar pathways to cross the double-membrane of Gram-negative bacteria and reach their intracellular targets, which they also can share. Consequently, bacteria may use common mechanisms of resistance against microcins and antibiotics. This review describes both unmodified and modified microcins [lasso peptides, siderophore peptides, nucleotide peptides, linear azole(in)e-containing peptides], highlighting their potential as weapons to thwart bacterial resistance in Gram-negative pathogens and discusses the possibility of cross-resistance and co-resistance occurrence between antibiotics and microcins in Gram-negative bacteria.202033240239
884940.9990Attenuating the Selection of Vancomycin Resistance Among Enterococci through the Development of Peptide-Based Vancomycin Antagonists. The emergence and spread of multidrug resistant (MDR) pathogens with acquired resistance to almost all available antimicrobial agents has severely threatened the international healthcare community over the last two decades. The last resort antibiotic vancomycin is critical for treatment of several of these pathogens; howeverc vancomycin resistance is spreading due to the undesired accumulation of IV vancomycin in the colon post-treatment. This accumulation exerts selective pressure upon members of the colonic microflora, including Enterococci, which possess vancomycin resistance genes. To ensure the continual effectiveness of vancomycin in the clinical setting by preventing the spread of antibiotic resistance, it is crucial to develop strategies that reduce selective pressure on the colonic microflora while allowing vancomycin to maintain its desired activity at the site of infection. Herein we report that modification of the native l-Lys-d-Ala-d-Ala vancomycin binding site can be used to produce peptides with the ability to competitively bind vancomycin, reducing its activity against susceptible Enterococci. Moreover, several modifications to the N-termini of the native tripeptide have produced compounds with enhanced vancomycin binding activity, including several analogs that were designed to covalently bind vancomycin, thereby acting as suicide inhibitors. Finally, in a mixed culture of susceptible and resistant bacteria, a single lead compound was found to protect high ratios of susceptible bacteria from vancomycin over the course of a week-long period, preventing the selection for vancomycin-resistant Enterococci. These findings demonstrate the ability of these peptides as potential therapeutic adjuvants for counteracting the undesired accumulation of colonic vancomycin, allowing for protection of the colonic microflora.202032946213
952850.9990Polycarbonates with Potent and Selective Antimicrobial Activity toward Gram-Positive Bacteria. The resistance developed by life-threatening bacteria toward conventional antibiotics has become a major concern in public health. To combat antibiotic resistance, there has been a significant interest in the development of antimicrobial cationic polymers due to the ease of synthesis and low manufacturing cost compared to host-defense peptides (HDPs). Herein, we report the design and synthesis of amphiphilic polycarbonates containing primary amino groups. These polymers exhibit potent antimicrobial activity and excellent selectivity to Gram-positive bacteria, including multidrug resistant pathogens. Fluorescence and TEM studies suggest that these polymers are likely to kill bacteria by disrupting bacterial membranes. These polymers also show low tendency to elicit resistance in bacteria. Their further development may lead to new antimicrobial agents combating drug-resistance.201728064500
909160.9990Characterization of an Enterococcus faecalis Bacteriophage vB_EfaM_LG1 and Its Synergistic Effect With Antibiotic. Enterococcus faecalis is a Gram-positive opportunistic pathogen that could cause pneumonia and bacteremia in stroke patients. The development of antibiotic resistance in hospital-associated E. faecalis is a formidable public health threat. Bacteriophage therapy is a renewed solution to treat antibiotic-resistant bacterial infections. However, bacteria can acquire phage resistance quite quickly, which is a significant barrier to phage therapy. Here, we characterized a lytic E. faecalis bacteriophage Vb_EfaM_LG1 with lytic activity. Its genome did not contain antibiotic resistance or virulence genes. Vb_EfaM_LG1 effectively inhibits E. faecalis growth for a short period, and phage resistance developed within hours. However, the combination of antibiotics and phage has a tremendous synergistic effect against E. faecalis, prevents the development of phage resistance, and disrupts the biofilm efficiently. Our results show that the phage-antibiotic combination has better killing efficiency against E. faecalis.202134336721
947670.9990Phage design and directed evolution to evolve phage for therapy. Phage therapy or Phage treatment is the use of bacteriolysing phage in treating bacterial infections by using the viruses that infects and kills bacteria. This technique has been studied and practiced very long ago, but with the advent of antibiotics, it has been neglected. This foregone technique is now witnessing a revival due to development of bacterial resistance. Nowadays, with the awareness of genetic sequence of organisms, it is required that informed choices of phages have to be made for the most efficacious results. Furthermore, phages with the evolving genes are taken into consideration for the subsequent improvement in treating the patients for bacterial diseases. In addition, direct evolution methods are increasingly developing, since these are capable of creating new biological molecules having changed or unique activities, such as, improved target specificity, evolution of novel proteins with new catalytic properties or creation of nucleic acids that are capable of recognizing required pathogenic bacteria. This system is incorporates continuous evolution such as protein or genes are put under continuous evolution by providing continuous mutagenesis with least human intervention. Although, this system providing continuous directed evolution is very effective, it imposes some challenges due to requirement of heavy investment of time and resources. This chapter focuses on development of phage as a therapeutic agent against various bacteria causing diseases and it improvement using direct evolution of proteins and nucleic acids such that they target specific organisms.202337739551
950780.9990Bacteriocins: Classification, synthesis, mechanism of action and resistance development in food spoilage causing bacteria. Huge demand of safe and natural preservatives has opened new area for intensive research on bacteriocins to unravel the novel range of antimicrobial compounds that could efficiently fight off the food-borne pathogens. Since food safety has become an increasingly important international concern, the application of bacteriocins from lactic acid bacteria that target food spoilage/pathogenic bacteria without major adverse effects has received great attention. Different modes of actions of these bacteriocins have been suggested and identified, like pore-forming, inhibition of cell-wall/nucleic acid/protein synthesis. However, development of resistance in the food spoilage and pathogenic bacteria against these bacteriocins is a rising concern. Emergence and spread of mutant strains resistant to bacteriocins is hampering food safety. It has spurred an interest to understand the bacteriocin resistance phenomenon displayed by the food pathogens, which will be helpful in mitigating the resistance problem. Therefore, present review is focused on the different resistance mechanisms adopted by food pathogens to overcome bacteriocin.201930610901
954690.9990Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria. Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list.202134064302
9748100.9990Resistance in antimicrobial photodynamic inactivation of bacteria. Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can "escape" more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria.201526098395
8851110.9990Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy. The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene's sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities.201627631336
9506120.9990Nisin resistance in Gram-positive bacteria and approaches to circumvent resistance for successful therapeutic use. Antibiotic resistance among bacterial pathogens is one of the most worrying problems in health systems today. To solve this problem, bacteriocins from lactic acid bacteria, especially nisin, have been proposed as an alternative for controlling multidrug-resistant bacteria. Bacteriocins are antimicrobial peptides that have activity mainly against Gram-positive strains. Nisin is one of the most studied bacteriocins and is already approved for use in food preservation. Nisin is still not approved for human clinical use, but many in vitro studies have shown its therapeutic effectiveness, especially for the control of antibiotic-resistant strains. Results from in vitro studies show the emergence of nisin-resistant bacteria after exposure to nisin. Considering that nisin has shown promising results for clinical use, studies to elucidate nisin-resistant mechanisms and the development of approaches to circumvent nisin-resistance are important. Thus, the objectives of this review are to identify the Gram-positive bacterial strains that have shown resistance to nisin, describe their resistance mechanisms and propose ways to overcome the development of nisin-resistance for its successful clinical application.202133689548
9121130.9990The role of efflux pumps ın antıbıotıc resıstance of gram negatıve rods. Antibiotic resistance is an important public health problem today, causing increased morbidity and mortality. Resistance to antibiotics in bacteria can develop by various mechanisms such as a change in the target site of the drug, a change in the outer membrane permeability, enzymatic defusing of the drug and efflux of the antimicrobial compound. Some bacteria have the potential to develop resistance to more than one drug by using several mechanisms together. One of the important resistance mechanisms of bacteria is active efflux pumps (EPs). EPs are pump proteins found in all cell types, located in the cell membrane. They are responsible for the excretion of various intracellular and extracellular substances (antibiotics, etc.) out of the cell. There is much research on various antimicrobials that cause antibiotic resistance in Gram negative rods, but studies on EPs are relatively few. Due to the concern that antibiotics will be insufficient in the treatment of diseases, a good understanding of EPs and the discovery of new EP inhibitors will shed light on the future of humanity. In this review, the structure of bacterial EPs in Gram negative bacteria, the role of EPs in multidrug resistance, the importance of EP inhibitors in the fight against antibiotic resistance and the phenotypic and genotypic detection methods of EPs are discussed.202337060362
4433140.9990The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria. A last line of defence against "superbugs" are the vancomycin group antibiotics. This review describes the determination of their mode of action, and a mechanism of resistance to them. Remarkably, this mechanism of resistance can be overcome without directly modifying the binding site of the antibiotics for the cell-wall precursors of pathogenic bacteria.199929711719
9547150.9990Confronting antibiotic-resistant pathogens: Distinctive drug delivery potentials of progressive nanoparticles. Antimicrobial resistance arises over time, usually due to genetic modifications. Global observations of high resistance rates to popular antibiotics used to treat common bacterial diseases, such as diarrhea, STIs, sepsis, and urinary tract infections, indicate that our supply of effective antibiotics is running low. The mechanisms of action of several antibiotic groups are covered in this review. Antimicrobials disrupt the development and metabolism of bacteria, leading to their eventual death. However, in recent years, microorganisms become resistant to the drugs. Bacteria encode resistant genes against antibiotics and inhibit the function of antibiotics by reducing the uptake of drugs, modifying the enzyme's active site, synthesizing enzymes to degrade antibiotics, and changing the structure of ribosomal subunits. Additionally, the methods of action of resistant bacteria against different kinds of antibiotics as well as their modes of action are discussed. Besides, the resistant pathogenic bacteria which get the most priority by World Health Organisation (WHO) for synthesizing new drugs, have also been incorporated. To overcome antimicrobial resistance, nanomaterials are used to increase the efficacy of antimicrobial drugs. Metallic, inorganic, and polymer-based nanoparticles once conjugated with antibacterial drugs, exhibit synergistic effects by increasing the efficacy of the drugs by inhibiting bacterial growth. Nanomaterial's toxic properties are proportional to their concentrations. Higher concentration nanomaterials are more toxic to the cells. In this review, the toxic properties of nanomaterials on lung cells, lymph nodes, and neuronal cells are also summarized.202438097117
9508160.9990Nisin and class IIa bacteriocin resistance among Listeria and other foodborne pathogens and spoilage bacteria. Food safety has been an important issue globally due to increasing foodborne diseases and change in food habits. To inactivate foodborne pathogens, various novel technologies such as biopreservation systems have been studied. Bacteriocins are ribosomally synthesized peptides or proteins with antimicrobial activity produced by different groups of bacteria, but the bacteriocins produced by many lactic acid bacteria offer potential applications in food preservation. The use of bacteriocins in the food industry can help reduce the addition of chemical preservatives as well as the intensity of heat treatments, resulting in foods that are more naturally preserved. However, the development of highly tolerant and/or resistant strains may decrease the efficiency of bacteriocins as biopreservatives. Several mechanisms of bacteriocin resistance development have been proposed among various foodborne pathogens. The acquiring of resistance to bacteriocins can significantly affect physiological activity profile of bacteria, alter cell-envelope lipid composition, and also modify the antibiotic susceptibility/resistance profile of bacteria. This article presents a brief review on the scientific research about the various possible mechanisms involved in the development of resistance to nisin and Class IIa bacteriocins among the foodborne pathogens.201121417775
9097170.9989Antimicrobial peptides with symmetric structures against multidrug-resistant bacteria while alleviating antimicrobial resistance. In response to the dramatically increasing antimicrobial resistance, a series of new symmetric peptides were designed and synthesized in this study by a "WWW" motif as the symmetric center, arginine as the positive charge amino acid and the terminus symmetrically tagged with hydrophobic amino acids. Amongst the new symmetric peptide FRRW (FRRWWWRRF-NH(2)) presented the highest cell selectivity for bacteria over mammalian cell and exerted excellent antimicrobial potential against a broad of bacteria, especially difficult-to-kill multidrug-resistant strains clinical isolates. FRRW also displayed perfect stability in physiological salt ions and rapid killing speed as well as acted on multiple mechanisms including non-receptor mediated membrane and intra-molecular mechanisms. Importantly, FRRW emerged a low tendency of resistance in contrast to traditional antibiotics ciprofloxacin and gentamicin. What's more, FRRW could resist or alleviate or even reverse the ciprofloxacin- and gentamicin-resistance by changing the permeability of bacterial membrane and inhibiting the efflux pumps of bacteria. Furthermore, FRRW exhibited remarkable effectiveness and higher safety in vivo than polymyxin B. In summary, the new symmetric peptide FRRW was promised to be as a new antimicrobial candidate for overcoming the increasing bacterial resistance.202133610592
4252180.9989Extreme antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance.201122919572
4251190.9989Extreme antimicrobial Peptide and polymyxin B resistance in the genus burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance.201121811491