Proteobiotics as a new antimicrobial therapy. - Related Documents




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946001.0000Proteobiotics as a new antimicrobial therapy. Antibiotic resistance is a major concern for healthcare. The emergence of resistant bacteria has contributed to an increase in cost, morbidity, and mortality rates of patients. There is evidence to suggest that the inhibition of bacteria's virulence strategies would downregulate their pathogenesis and stop infections while also preventing more resistance. This concept became the backbone of many studies in the arena of human microbiome. Through probiotic studies, novel compounds were discovered that possessed antimicrobial activity. These have become labeled as proteobiotics, i.e. metabolites from probiotics. Proteobiotics have demonstrated the ability to interrupt bacteria cell-to-cell communication. Currently, there is one approved product containing proteobiotic technologies for swine showing positive outcomes.202032109571
956210.9997Fight against antimicrobial resistance. Antimicrobial and antibiotic resistance is ever increasing and the fight against it is a battle that can never be won. Nevertheless, some possibilities exist to improve this situation, at least in part. The present review article discusses some approaches that can be used to control microbial resistance. Possible strategies are (1) designing new vaccines against resistant bacterial strains; (2) investigation of the potential of both traditional and non-traditional sources of natural substances for use as new antibiotics; (3) search for genes specifying biosynthesis of antibiotics; (4) use of forgotten natural compounds and their transformation, and (5) investigation of new antibiotic targets in pathogenic bacteria. Particular attention is paid to the search for new compounds that would be able to inhibit pathogenic bacteria resistant to existing antibiotics.201830126284
424320.9996Action and resistance mechanisms of antibiotics: A guide for clinicians. Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and "bypass" of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.201729109626
954330.9996Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria. Despite the availability of antibiotics and vaccines, infectious diseases remain one of most dangerous threats to humans and animals. The overuse and misuse of antibacterial agents have led to the emergence of multidrug resistant bacterial pathogens. Bacterial cells are often resilient enough to survive in even the most extreme environments. To do so, the organisms have evolved different mechanisms, including a variety of two-component signal transduction systems, which allow the bacteria to sense the surrounding environment and regulate gene expression in order to adapt and respond to environmental stimuli. In addition, some bacteria evolve resistance to antibacterial agents while many bacterial cells are able to acquire resistance genes from other bacterial species to enable them to survive in the presence of toxic antimicrobial agents. The crisis of antimicrobial resistance is an unremitting menace to human health and a burden on public health. The rapid increase in antimicrobial resistant organisms and limited options for development of new classes of antibiotics heighten the urgent need to develop novel potent antibacterial therapeutics in order to combat multidrug resistant infections. In this review, we introduce the regulatory mechanisms of antisense RNA and significant applications of regulated antisense RNA interference technology in early drug discovery. This includes the identification and evaluation of drug targets in vitro and in vivo, the determination of mode of action for antibiotics and new antibacterial agents, as well as the development of peptide-nucleic acid conjugates as novel antibacterials.201323738437
424540.9996Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets.202031659373
912750.9996Antimicrobial Peptides: Virulence and Resistance Modulation in Gram-Negative Bacteria. Growing resistance to antibiotics is one of the biggest threats to human health. One of the possibilities to overcome this resistance is to use and develop alternative molecules such as antimicrobial peptides (AMPs). However, an increasing number of studies have shown that bacterial resistance to AMPs does exist. Since AMPs are immunity molecules, it is important to ensure that their potential therapeutic use is not harmful in the long term. Recently, several studies have focused on the adaptation of Gram-negative bacteria to subinhibitory concentrations of AMPs. Such concentrations are commonly found in vivo and in the environment. It is therefore necessary to understand how bacteria detect and respond to low concentrations of AMPs. This review focuses on recent findings regarding the impact of subinhibitory concentrations of AMPs on the modulation of virulence and resistance in Gram-negative bacteria.202032092866
947360.9996The role of the animal host in the management of bacteriophage resistance during phage therapy. Multi-drug-resistant bacteria are associated with significantly higher morbidity and mortality. The possibilities for discovering new antibiotics are limited, but phage therapy - the use of bacteriophages (viruses infecting bacteria) to cure infections - is now being investigated as an alternative or complementary treatment to antibiotics. However, one of the major limitations of this approach lies in the antagonistic coevolution between bacteria and bacteriophages, which determines the ultimate success or failure of phage therapy. Here, we review the possible influence of the animal host on phage resistance and its consequences for the efficacy of phage therapy. We also discuss the value of in vitro assays for anticipating the dynamics of phage resistance observed in vivo.202336512896
949570.9996Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs. Antibiotic resistance is a global threat that should be urgently resolved. Finding a new antibiotic is one way, whereas the repression of the dissemination of virulent pathogenic bacteria is another. From this point of view, this paper summarizes first the mechanisms of conjugation and transformation, two important processes of horizontal gene transfer, and then discusses the approaches for disarming virulent pathogenic bacteria, that is, virulence factor inhibitors. In contrast to antibiotics, anti-virulence drugs do not impose a high selective pressure on a bacterial population, and repress the dissemination of antibiotic resistance and virulence genes. Disarmed virulence factors make virulent pathogens avirulent bacteria or pathobionts, so that we human will be able to coexist with these disarmed bacteria peacefully.202132647212
912680.9996The Exploration of Complement-Resistance Mechanisms of Pathogenic Gram-Negative Bacteria to Support the Development of Novel Therapeutics. Resistance to antibiotics in Bacteria is one of the biggest threats to human health. After decades of attempting to isolate or design antibiotics with novel mechanisms of action against bacterial pathogens, few approaches have been successful. Antibacterial drug discovery is now moving towards targeting bacterial virulence factors, especially immune evasion factors. Gram-negative bacteria present some of the most significant challenges in terms of antibiotic resistance. However, they are also able to be eliminated by the component of the innate immune system known as the complement system. In response, Gram-negative bacteria have evolved a variety of mechanisms by which they are able to evade complement and cause infection. Complement resistance mechanisms present some of the best novel therapeutic targets for defending against highly antibiotic-resistant pathogenic bacterial infections.202236015050
954190.9996The Role of the Hfq Protein in Bacterial Resistance to Antibiotics: A Narrative Review. The antibiotic resistance of pathogenic microorganisms is currently one of most major medical problems, causing a few million deaths every year worldwide due to untreatable bacterial infections. Unfortunately, the prognosis is even worse, as over 8 million deaths associated with antibiotic resistance are expected to occur in 2050 if no new effective antibacterial treatments are discovered. The Hfq protein has been discovered as a bacterial RNA chaperone. However, subsequent studies have indicated that this small protein (composed of 102 amino acid residues in Escherichia coli) has more activities, including binding to DNA and influencing its compaction, interaction with biological membranes, formation of amyloid-like structures, and others. Although Hfq is known to participate in many cellular processes, perhaps surprisingly, only reports from recent years have demonstrated its role in bacterial antibiotic resistance. The aim of this narrative review is to discuss how can Hfq affects antibiotic resistance in bacteria and propose how this knowledge may facilitate developing new therapeutic strategies against pathogenic bacteria. We indicate that the mechanisms by which the Hfq protein modulates the response of bacterial cells to antibiotics are quite different, from the regulation of the expression of genes coding for proteins directly involved in antibiotic transportation or action, through direct effects on membranes, to controlling the replication or transposition of mobile genetic elements bearing antibiotic resistance genes. Therefore, we suggest that Hfq could be considered a potential target for novel antimicrobial compounds. We also discuss difficulties in developing such drugs, but since Hfq appears to be a promising target for drugs that may enhance the efficacy of antibiotics, we propose that works on such potential therapeutics are encouraged.202540005731
9459100.9996Effects of Itxasol© Components on Gene Expression in Bacteria Related to Infections of the Urinary Tract and to the Inflammation Process. Urinary tract infections (UTIs) represent a health problem of the first magnitude since they affect large segments of the population, cause increased mortality and comorbidity, and have a high incidence of relapse. Therefore, UTIs cause a major socioeconomic concern. Current antibiotic treatments have various limitations such as the appearance of resistance to antibiotics, nephrotoxicity, and side effects such as gastrointestinal problems including microbiota alterations that contribute to increasing antibiotic resistance. In this context, Itxasol© has emerged, approved as an adjuvant for the treatment of UTIs. Designed with biomimetic principles, it is composed of arbutin, umbelliferon, and N-acetyl cysteine. In this work, we review the activities of these three compounds concerning the changes they produce in the expression of bacterial genes and those related to inflammation as well as assess how they are capable of affecting the DNA of bacteria and fungi.202134884459
4244110.9996Molecular mechanisms of antibiotic resistance. Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.201525435309
4242120.9996The basis of antibiotic resistance in bacteria. The ability of bacteria to resist the inhibitory and lethal actions of antibiotics is a major clinical problem, and has been observed with every antimicrobial agent. In this article, the major mechanisms of antibiotic resistance are reviewed, and the clinical relevance of such resistance in selected bacteria is discussed.19902192071
9520130.9996Role of Natural Product in Modulation of Drug Transporters and New Delhi Metallo-β Lactamases. A rapid growth in drug resistance has brought options for treating antimicrobial resistance to a halt. Bacteria have evolved to accumulate a multitude of genes that encode resistance for a single drug within a single cell. Alternations of drug transporters are one of the causes for the development of resistance in drug interactions. Conversely, the production of enzymes also inactivates most antibiotics. The discovery of newer classes of antibiotics and drugs from natural products is urgently needed. Alternative medicines play an integral role in countries across the globe but many require validation for treatment strategies. It is essential to explore this chemical diversity in order to find novel drugs with specific activities which can be used as alternative drug targets. This review describes the interaction of drugs with resistant pathogens with a special focus on natural product-derived efflux pump and carbapenemase inhibitors.201930987566
9597140.9996Role of xenobiotic transporters in bacterial drug resistance and virulence. Since the discovery of antibiotic therapeutics, the battles between humans and infectious diseases have never been stopped. Humans always face the appearance of a new bacterial drug-resistant strain followed by new antibiotic development. However, as the genome sequences of infectious bacteria have been gradually determined, a completely new approach has opened. This approach can analyze the entire gene resources of bacterial drug resistance. Through analysis, it may be possible to discover the underlying mechanism of drug resistance that will appear in the future. In this review article, we will first introduce the method to analyze all the xenobiotic transporter genes by using the genomic information. Next, we will discuss the regulation of xenobiotic transporter gene expression through the two-component signal transduction system, the principal environmental sensing and response system in bacteria. Furthermore, we will also introduce the virulence roles of xenobiotic transporters, which is an ongoing research area.200818481812
9418150.9996Vibrio cholerae infection, novel drug targets and phage therapy. Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.201122004038
9469160.9996Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Pathogen resistance to antibiotics is a rapidly growing problem, leading to an urgent need for novel antimicrobial agents. Unfortunately, development of new antibiotics faces numerous obstacles, and a method that resensitizes pathogens to approved antibiotics therefore holds key advantages. We present a proof of principle for a system that restores antibiotic efficiency by reversing pathogen resistance. This system uses temperate phages to introduce, by lysogenization, the genes rpsL and gyrA conferring sensitivity in a dominant fashion to two antibiotics, streptomycin and nalidixic acid, respectively. Unique selective pressure is generated to enrich for bacteria that harbor the phages carrying the sensitizing constructs. This selection pressure is based on a toxic compound, tellurite, and therefore does not forfeit any antibiotic for the sensitization procedure. We further demonstrate a possible way of reducing undesirable recombination events by synthesizing dominant sensitive genes with major barriers to homologous recombination. Such synthesis does not significantly reduce the gene's sensitization ability. Unlike conventional bacteriophage therapy, the system does not rely on the phage's ability to kill pathogens in the infected host, but instead, on its ability to deliver genetic constructs into the bacteria and thus render them sensitive to antibiotics prior to host infection. We believe that transfer of the sensitizing cassette by the constructed phage will significantly enrich for antibiotic-treatable pathogens on hospital surfaces. Broad usage of the proposed system, in contrast to antibiotics and phage therapy, will potentially change the nature of nosocomial infections toward being more susceptible to antibiotics rather than more resistant.201222113912
9563170.9996Do we need new antibiotics? The search for new targets and new compounds. Resistance to antibiotics and other antimicrobial compounds continues to increase. There are several possibilities for protection against pathogenic microorganisms, for instance, preparation of new vaccines against resistant bacterial strains, use of specific bacteriophages, and searching for new antibiotics. The antibiotic search includes: (1) looking for new antibiotics from nontraditional or less traditional sources, (2) sequencing microbial genomes with the aim of finding genes specifying biosynthesis of antibiotics, (3) analyzing DNA from the environment (metagenomics), (4) re-examining forgotten natural compounds and products of their transformations, and (5) investigating new antibiotic targets in pathogenic bacteria.201021086099
9465180.9996Antimicrobial drug resistance: "Prediction is very difficult, especially about the future". Evolution of bacteria towards resistance to antimicrobial drugs, including multidrug resistance, is unavoidable because it represents a particular aspect of the general evolution of bacteria that is unstoppable. Therefore, the only means of dealing with this situation is to delay the emergence and subsequent dissemination of resistant bacteria or resistance genes. Resistance to antimicrobial drugs in bacteria can result from mutations in housekeeping structural or regulatory genes. Alternatively, resistance can result from the horizontal acquisition of foreign genetic information. The 2 phenomena are not mutually exclusive and can be associated in the emergence and more efficient spread of resistance. This review discusses the predictable future of the relationship between antimicrobial drugs and bacteria.200516318687
9464190.9996Why is antibiotic resistance a deadly emerging disease? Evolution of bacteria towards resistance to antimicrobial agents, including multidrug resistance, is unavoidable because it represents a particular aspect of the general evolution of bacteria that is unstoppable. Therefore, the only means of dealing with this situation is to delay the emergence and subsequent dissemination of resistant bacteria or resistance genes. In this review, we will consider the biochemical mechanisms and the genetics that bacteria use to offset antibiotic selective pressure. The data provided are mainly, if not exclusively, taken from the work carried out in the laboratory, although there are numerous other examples in the literature.201626806259