Progress in Molecular Biology and Translational Science最新文献

The over usage of antibiotics leads to antibiotic abuse which in turn eventually raises resistance mechanisms among wide range of pathogens. Due to lack of experimental data of efficacy of phages as potential antimicrobial and therapeutic agent and also more specific and cumbersome isolation process against specific pathogens makes it not so feasible technology to be looked as an alternative therapy. But, recent developments in genome editing techniques enables programmed nuclease enzymes that has effectively improvised our methodology to make accurate changes in the genomes of prokaryote as well as eukaryote cells. It is already strengthening our ability to improvise genetic engineering to disease identification by facilitating the creation of more precise models to identify the root cause. The present chapter discusses on improvisation of phage therapy using recent genome editing tools and also shares data on the methods of usage of phages and their derivatives like proteins and enzymes such as lysins and depolymerases, as a potential therapeutic or prophylaxis agent. Methods involved in recombinant based techniques were also discussed in this chapter. Combination of traditional approach with modern tools has led to a potential development of phage-based therapeutics in near future.

Bacteriophages (Phages in short) were introduced as the natural enemy of bacteria that may act as alternatives to antibiotics to overcome the challenge of antibiotic resistance. However, in the recent history of science, phages have been employed in different molecular tools and used in numerous therapeutic and diagnostic approaches. Furthermore, thanks to the phage`s highly specific host range limited to prokaryotes, phage particles can be used as safe delivery vehicles and display systems. In this chapter, different phage display systems are introduced, in addition to various applications of phage display as a molecular and therapeutic tool in developing vaccines, antibacterial, and anti-cancer treatments.

Highly drug-resistant strains are not uncommon among the Mycobacterium genus, with patients requiring lengthy antibiotic treatment regimens with multiple drugs and harmful side effects. This alarming increase in antibiotic resistance globally has renewed the interest in mycobacteriophage therapy for both Mycobacterium tuberculosis complex and non-tuberculosis mycobacteria. With the increasing number of genetically well-characterized mycobacteriophages and robust engineering tools to convert temperate phages to obligate lytic phages, the phage cache against extensive drug-resistant mycobacteria is constantly expanding. Synergistic effects between phages and TB drugs are also a promising avenue to research, with mycobacteriophages having several additional advantages compared to traditional antibiotics due to their different modes of action. These advantages include less side effects, a narrow host spectrum, biofilm penetration, self-replication at the site of infection and the potential to be manufactured on a large scale. In addition, mycobacteriophage enzymes, not yet in clinical use, warrant further studies with their additional benefits for rupturing host bacteria thereby limiting resistance development as well as showing promise in vitro to act synergistically with TB drugs. Before mycobacteriophage therapy can be envisioned as part of routine care, several obstacles must be overcome to translate in vitro work into clinical practice. Strategies to target intracellular bacteria and selecting phage cocktails to limit cross-resistance remain important avenues to explore. However, insight into pathophysiological host-phage interactions on a molecular level and innovative solutions to transcend mycobacteriophage therapy impediments, offer sufficient encouragement to explore phage therapy. Recently, the first successful clinical studies were performed using a mycobacteriophage-constructed cocktail to treat non-tuberculosis mycobacteria, providing substantial insight into lessons learned and potential pitfalls to avoid in order to ensure favorable outcomes. However, due to mycobacterium strain variation, mycobacteriophage therapy remains personalized, only being utilized in compassionate care cases until there is further regulatory approval. Therefore, identifying the determinants that influence clinical outcomes that can expand the repertoire of mycobacteriophages for therapeutic benefit, remains key for their future application.

Phage display is a significant and active molecular method and has continued crucial for investigative sector meanwhile its unearthing in 1985. This practice has numerous benefits: the association among physiology and genome, the massive variety of variant proteins showed in sole collection and the elasticity of collection that can be achieved. It suggests a diversity of stages for manipulating antigen attachment; yet, variety and steadiness of exhibited library are an alarm. Additional improvements, like accumulation of non-canonical amino acids, resulting in extension of ligands that can be recognized through collection, will support in expansion of the probable uses and possibilities of technology. Epidemic of COVID-19 had taken countless lives, and while indicative prescriptions were provided to diseased individuals, still no prevention was observed for the contamination. Phage demonstration has presented an in-depth understanding into protein connections included in pathogenesis. Phage display knowledge is developing as an influential, inexpensive, quick, and effectual method to grow novel mediators for the molecular imaging and analysis of cancer.

Synthetic phage analysis has been implemented in progressive various areas of biology, such as genetics, molecular biology, and synthetic biology. Many phage-derived technologies have been altered for developing gene circuits to program biological systems. Due to their extremely potent potency, phages also provide greater medical availability against bacterial agents and bacterial diagnostic agents. Its host specificity and our growing ability to manipulate, them further expand its possibility. New Phages also genetically redesign programmable biomaterials with highly tunable properties. Moreover, new phages are central to powerful directed evolution platforms. It is used to enhance existing biological, functions to create new phages. In other sites, the mining of antibiotics, and the emergence and dissemination of more than one type of drug-resistant microbe, a human health concerns. The major point in controlling and treating microbial infections. At present, genetic modifications and biochemical treatments are used to modify phages. Among these, genetic engineering involves the identification of defective proteins, modification of host bodies, recognized receptors, and disruption of bacterial phage resistance signaling gateways.

Cancer is currently a global health challenge, characterized by dysfunction of organs due to the uncontrolled growth of cells exponentially. The therapies used to treat cancer in patients so far are widely used. However, there are also some problems, such as the high cost of surgery and chemotherapy. Thus, there are many barriers to care for patients with cancer, especially in low and middle-income countries. In addition, the many risks and adverse effects of radiation treatment. Therefore, to reduce mortality in patients with the disease, we need a newer therapy with more targeted treatment, fewer side effects, and cheaper cost. The application of bacteria in cancer treatment was first developed in 1983. Currently, this therapy is attracting the attention of scientists due to its great potential in cancer treatment. This chapter discusses the successful research on the bacteriophage for cancer, the mechanism and its potential. In addition, some types of bacteria that are most important for cancer treatment and limitations on the widespread application of this therapy were also mentioned. Reviewing all the researches on bacteriotherapy in cancer are essential to increase the knowledge in this area and make this therapy more optimal in the future.

Klebsiella pneumoniae is an opportunistic pathogen involved in both hospital- and community-acquired infections. K. pneumoniae is associated with various infections, including pneumonia, septicemia, meningitis, urinary tract infection, and surgical wound infection. K. pneumoniae possesses serious virulence, biofilm formation ability, and severe resistance to many antibiotics especially hospital-acquired strains, due to excessive use in healthcare systems. This limits the available effective antibiotics that can be used for patients suffering from K. pneumoniae infections; therefore, alternative treatments are urgently needed. Bacteriophages (for short, phages) are prokaryotic viruses capable of infecting, replicating, and then lysing (lytic phages) the bacterial host. Phage therapy exhibited great potential for treating multidrug-resistant bacterial infections comprising K. pneumoniae. Hence, this chapter emphasizes and summarizes the research articles in the PubMed database from 1948 until the 15th of December 2022, addressing phage therapy against K. pneumoniae. The chapter provides an overview of K. pneumoniae phages covering different aspects, including phage isolation, different morphotypes of isolated phages, in vitro characterization, anti-biofilm activity, various therapeutic forms, in vivo research and clinical studies.

Acinetobacter is a gram-negative nosocomial pathogenic bacteria. The contributing factor for the pathogenicity of Acinetobacter is severe due to its property of antibacterial drug resistance. Often antibiotic treatment is used to treat bacterial infection, however due to the resistance of a broad range of antibiotics by Acinetobacter the treatment viability of this bacterial species seems to be reduced. To combat this diverse treatment options are being incorporated with phage therapy being an effective choice due to its intrinsic property to infect bacteria. In this chapter the various phage therapy used in recent times has been elaborated on. The phage therapy is considered to be in response to Carbapenem resistance. The various mode of phage propagation has been mentioned in this chapter along with the type of resistance conferred to the administered therapy. The chapter deals with the advances observed due to therapy of Acibel004, Acibel007, vB-GEC_Ab-M-G7, ZZ1 and Bacteriophage p54 containing Endolysin LysAB54 bacteriophages have been elucidated.

Phage are drivers of numerous ecological processes on the planet and have the potential to be developed into a therapy alternative to antibiotics. Phage at all points of their life cycle, from initiation of infection to their release, interact with their host in some manner. More importantly, to harness their antimicrobial potential it is vital to understand how phage interact with the eukaryotic environment in the context of applying phage for therapy. In this chapter, the various mechanisms of phage interplay with their hosts as part of their natural life cycle are discussed in depth for Gram-positive and negative bacteria. Further, the literature surrounding the various models utilized to develop phage as a therapeutic are examined, and how these models may improve our understanding of phage-host interactions and current progress in utilizing phage for therapy in the clinical environment.

Pseudomonas aeruginosa is denoted as one of the highly threatening bacteria to the public health. It has acquired many virulent factors and resistant genes that make it difficult to control with conventional antibiotics. Thus, bacteriophage therapy (phage therapy) is a proposed alternative to antibiotics to fight against multidrug-resistant P. aeruginosa. Many phages have been isolated that exhibit a broad spectrum of activity against P. aeruginosa. In this chapter, the common virulent factors and the prevalence of antibiotic-resistance genes in P. aeruginosa were reported. In addition, recent efforts in the field of phage therapy against P. aeruginosa were highlighted, including wild-type phages, genetically modified phages, phage cocktails, and phage in combination with antibiotics against P. aeruginosa in the planktonic and biofilm forms. Recent regulations on phage therapy were also covered in this chapter.