Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review. - Related Documents




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944501.0000Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review. Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a highly infectious disease and worldwide health problem. Based on the WHO TB report, 9 million active TB cases are emerging, leading to 2 million deaths each year. The recent emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains emphasizes the necessity to improve novel therapeutic plans. Among the various developing antibacterial approaches, phage therapy is thought to be a precise hopeful resolution. Mycobacteriophages are viruses that infect bacteria such as Mycobacterium spp., containing the M. tuberculosis complex. Phages and phage-derived proteins can act as promising antimicrobial agents. Also, phage cocktails can broaden the spectrum of lysis activity against bacteria. Recent researches have also shown the effective combination of antibiotics and phages to defeat the infective bacteria. There are limitations and concerns about phage therapy. For example, human immune response to phage therapy, transferring antibiotic resistance genes, emerging resistance to phages, and safety issues. So, in the present study, we introduced mycobacteriophages, their use as therapeutic agents, and their advantages and limitations as therapeutic applications.202236550444
944710.9998Modern vaccine development via reverse vaccinology to combat antimicrobial resistance. With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.202235642852
980420.9998Antimicrobial Peptides as an Alternative for the Eradication of Bacterial Biofilms of Multi-Drug Resistant Bacteria. Bacterial resistance is an emergency public health problem worldwide, compounded by the ability of bacteria to form biofilms, mainly in seriously ill hospitalized patients. The World Health Organization has published a list of priority bacteria that should be studied and, in turn, has encouraged the development of new drugs. Herein, we explain the importance of studying new molecules such as antimicrobial peptides (AMPs) with potential against multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteria and focus on the inhibition of biofilm formation. This review describes the main causes of antimicrobial resistance and biofilm formation, as well as the main and potential AMP applications against these bacteria. Our results suggest that the new biomacromolecules to be discovered and studied should focus on this group of dangerous and highly infectious bacteria. Alternative molecules such as AMPs could contribute to eradicating biofilm proliferation by MDR/XDR bacteria; this is a challenging undertaking with promising prospects.202235336016
944630.9998Newer antibiotics for the treatment of respiratory tract infections. PURPOSE OF REVIEW: In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. RECENT FINDINGS: Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. SUMMARY: Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse.200415071370
817940.9998Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives. The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.202336830949
944250.9998Antibiotic resistance. Antibiotic resistance poses serious challenges to health and national security, and policy changes will be required to mitigate the consequences of antibiotic resistance. Resistance can arise in disease-causing bacteria naturally, or it can be deliberately introduced to a biological weapon. In either case, life-saving drugs are rendered ineffective. Resistant bacterial infections are difficult to treat, and there are few new antibiotics in the drug development pipeline. This article describes how antibiotic resistance affects health and national security, how bacteria become antibiotic resistant, and what should be done now so antibiotics will be available to save lives in the future.200920028245
918360.9998Overcoming Bacteriophage Resistance in Phage Therapy. Antibiotic resistance among pathogenic bacteria is one of the most severe global challenges. It is predicted that over ten million lives will be lost annually by 2050. Phage therapy is a promising alternative to antibiotics. However, the ease of development of phage resistance during therapy is a concern. This review focuses on the possible ways to overcome phage resistance in phage therapy.202437966611
954670.9997Challenge 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
944480.9997Prospects for the Use of New Technologies to Combat Multidrug-Resistant Bacteria. The increasing use of antibiotics is being driven by factors such as the aging of the population, increased occurrence of infections, and greater prevalence of chronic diseases that require antimicrobial treatment. The excessive and unnecessary use of antibiotics in humans has led to the emergence of bacteria resistant to the antibiotics currently available, as well as to the selective development of other microorganisms, hence contributing to the widespread dissemination of resistance genes at the environmental level. Due to this, attempts are being made to develop new techniques to combat resistant bacteria, among them the use of strictly lytic bacteriophage particles, CRISPR-Cas, and nanotechnology. The use of these technologies, alone or in combination, is promising for solving a problem that humanity faces today and that could lead to human extinction: the domination of pathogenic bacteria resistant to artificial drugs. This prospective paper discusses the potential of bacteriophage particles, CRISPR-Cas, and nanotechnology for use in combating human (bacterial) infections.201931293420
954590.9997MDR Pumps as Crossroads of Resistance: Antibiotics and Bacteriophages. At present, antibiotic resistance represents a global problem in modern medicine. In the near future, humanity may face a situation where medicine will be powerless against resistant bacteria and a post-antibiotic era will come. The development of new antibiotics is either very expensive or ineffective due to rapidly developing bacterial resistance. The need to develop alternative approaches to the treatment of bacterial infections, such as phage therapy, is beyond doubt. The cornerstone of bacterial defense against antibiotics are multidrug resistance (MDR) pumps, which are involved in antibiotic resistance, toxin export, biofilm, and persister cell formation. MDR pumps are the primary non-specific defense of bacteria against antibiotics, while drug target modification, drug inactivation, target switching, and target sequestration are the second, specific line of their defense. All bacteria have MDR pumps, and bacteriophages have evolved along with them and use the bacteria's need for MDR pumps to bind and penetrate into bacterial cells. The study and understanding of the mechanisms of the pumps and their contribution to the overall resistance and to the sensitivity to bacteriophages will allow us to either seriously delay the onset of the post-antibiotic era or even prevent it altogether due to phage-antibiotic synergy.202235740141
9440100.9997The Case against Antibiotics and for Anti-Virulence Therapeutics. Although antibiotics have been indispensable in the advancement of modern medicine, there are downsides to their use. Growing resistance to broad-spectrum antibiotics is leading to an epidemic of infections untreatable by first-line therapies. Resistance is exacerbated by antibiotics used as growth factors in livestock, over-prescribing by doctors, and poor treatment adherence by patients. This generates populations of resistant bacteria that can then spread resistance genes horizontally to other bacterial species, including commensals. Furthermore, even when antibiotics are used appropriately, they harm commensal bacteria leading to increased secondary infection risk. Effective antibiotic treatment can induce bacterial survival tactics, such as toxin release and increasing resistance gene transfer. These problems highlight the need for new approaches to treating bacterial infection. Current solutions include combination therapies, narrow-spectrum therapeutics, and antibiotic stewardship programs. These mediate the issues but do not address their root cause. One emerging solution to these problems is anti-virulence treatment: preventing bacterial pathogenesis instead of using bactericidal agents. In this review, we discuss select examples of potential anti-virulence targets and strategies that could be developed into bacterial infection treatments: the bacterial type III secretion system, quorum sensing, and liposomes.202134683370
9473110.9997The 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
8173120.9997Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes. One of the most significant issues facing the world today is antibiotic resistance, which makes it increasingly difficult to treat bacterial infections. Regular antibiotics no longer work against many bacteria, affecting millions of people. A novel approach known as CRISPR-phage therapy may be beneficial. This technique introduces a technology called CRISPR into resistant bacteria using bacteriophages. The genes that cause bacteria to become resistant to antibiotics can be identified and cut using CRISPR. This enables antibiotics to function by inhibiting the bacteria. This approach is highly precise, unlike conventional antibiotics, so it doesn't damage our bodies' beneficial bacteria. Preliminary studies and limited clinical trials suggest that this technique can effectively target drug-resistant bacteria such as Klebsiella pneumoniae and Methicillinresistant Staphylococcus aureus (MRSA). However, challenges in phage engineering, host delivery, and the growing threat of bacterial CRISPR resistance demand urgent and strategic innovation. Our perspective underscores that without proactive resolution of these hurdles, the current hopefulness could disappear. Looking ahead, integrating next-generation Cas effectors, non-DSB editors, and resistance monitoring frameworks could transform CRISPR-phage systems from an experimental novelty into a clinical mainstay. This shift will require not only scientific ingenuity but also coordinated advances in regulatory, translational, and manufacturing efforts.202540990280
9476130.9997Phage 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
9564140.9997Genomic tools to profile antibiotic mode of action. The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.201524617440
9184150.9997Unlocking the potential of phages: Innovative approaches to harnessing bacteriophages as diagnostic tools for human diseases. Phages, viruses that infect bacteria, have been explored as promising tools for the detection of human disease. By leveraging the specificity of phages for their bacterial hosts, phage-based diagnostic tools can rapidly and accurately detect bacterial infections in clinical samples. In recent years, advances in genetic engineering and biotechnology have enabled the development of more sophisticated phage-based diagnostic tools, including those that express reporter genes or enzymes, or target specific virulence factors or antibiotic resistance genes. However, despite these advancements, there are still challenges and limitations to the use of phage-based diagnostic tools, including concerns over phage safety and efficacy. This review aims to provide a comprehensive overview of the current state of phage-based diagnostic tools, including their advantages, limitations, and potential for future development. By addressing these issues, we hope to contribute to the ongoing efforts to develop safe and effective phage-based diagnostic tools for the detection of human disease.202337770168
9558160.9997Antimicrobial Resistance: Enzymes, Proteins, and Computational Resources. Antimicrobial resistance (AMR) is an important health concern rooted in antibiotic misuse and overuse, resulting in drug-resistant bacteria. However, resistance to these antimicrobials developed as soon as they were administered. Several variables lead to the progression of antimicrobial resistance (AMR), making it a multifaceted challenge for healthcare systems worldwide, such as erroneous diagnosis, inappropriate prescription, incomplete treatment, and many more. Getting an in-depth idea about the mechanism underlying AMR development is essential to overcome this. This review aims to provide information on how various enzymes or proteins aid in the antimicrobial resistance mechanisms and also highlight the clinical perspective of AMR, emphasizing its growing impact on patient outcomes, and incorporate the latest recent data from the World Health Organisation (WHO), underscoring the global urgency of the AMR crisis, with specific attention to trends observed in recent years. Additionally, it is intended to provide ideas about inhibitors that can inhibit the mechanism of antibiotic resistance and also to provide an idea about numerous computational resources available that can be employed to predict genes and/or proteins and enzymes involved in various antibiotic resistance mechanisms.202540770471
9796170.9997Bacteriophage therapy to combat MDR non-fermenting Gram-negative bacteria causing nosocomial infections: recent progress and challenges. Clinicians face significant challenges in managing nosocomial infections, primarily due to antimicrobial resistance in multidrug-resistant bacteria. Regardless of the availability of a wide range of antimicrobials in the market, resistance is escalating rampantly with every passing day, which has become a global concern. Hence, it is essential to discover new and more efficient techniques to eliminate pathogens from healthcare settings. Along with eliminating pathogenic bacteria, mitigating their antimicrobial resistance with novel methods is very essential. Recently, bacteriophages have re-emerged as a promising therapeutic alternative to treat serious infections caused by bacterial pathogens. Bacteriophages were discovered for the first time a century ago, but their usage has recently regained more attention in treating bacterial pathogens. Bacteriophages also help in mitigating the worldwide problem of antibiotic resistance, particularly augmented by Gram-negative bacteria. This review discussed the advancements in the usage of bacteriophages in combating the antimicrobial resistance of multidrug-resistant Gram-negative bacteria, with a prime focus on Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cepacia complex (Bcc), which are renowned non-fermenting Gram-negative bacteria (NFGNB) pathogens. Additionally, the effects of single phage, phage cocktails, and combination therapy with antibiotics on bacterial biofilms and polymicrobial biofilms are also discussed.202540478338
9543180.9997Antisense 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
9484190.9997Phage-antibiotic combinations: a promising approach to constrain resistance evolution in bacteria. Antibiotic resistance has reached dangerously high levels throughout the world. A growing number of bacteria pose an urgent, serious, and concerning threat to public health. Few new antibiotics are available to clinicians and only few are in development, highlighting the need for new strategies to overcome the antibiotic resistance crisis. Combining existing antibiotics with phages, viruses the infect bacteria, is an attractive and promising alternative to standalone therapies. Phage-antibiotic combinations have been shown to suppress the emergence of resistance in bacteria, and sometimes even reverse it. Here, we discuss the mechanisms by which phage-antibiotic combinations reduce resistance evolution, and the potential limitations these mechanisms have in steering microbial resistance evolution in a desirable direction. We also emphasize the importance of gaining a better understanding of mechanisms behind physiological and evolutionary phage-antibiotic interactions in complex in-patient environments.202133175408