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Lysis Protein
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Although solid data have been collected on the RNA phage lysis proteins to the Millennium time, Bernhardt et al. (2002) were forced to confess in their great review that the lysis mechanism by the RNA phage lysis proteins remained a mystery. Nevertheless, this review extended the concept of the protein antibiotics initiated by the A2 protein of the phage Qβ (Bernhardt et al. 2001) described in the Lysis section of Chapter 11 over the RNA phage lysis proteins. The term amurin was proposed for the lysis proteins that lacked muralytic activity but somehow subverted peptidoglycan integrity (Bernhardt et al. 2002). At that time, the A2 protein and the E protein of the phage φX174 as the first representatives of the protein antibiotics were numbered together with the putative phage therapy tools (Inal 2003). In fact, the concept of phage therapy to treat bacterial infections was born with the discovery of the bacteriophage almost a century ago but seemed barely acceptable to the RNA phages, whereas their lysis proteins gave some confidence to the possible application. Generally, the current renaissance of phage therapy was fueled by the dangerous appearance of antibiotic-resistant bacteria on a global scale, especially for human use.
Fundamentals
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
Now a day, antibiotic-resistant bacteria are becoming widespread. If there is a probability that a bacterium gets resistant to an antibiotic “A” is 0.02, and the probability that the same bacteria got resistant to another antibiotic that kills bacteria using different independent mechanism is 0.05. What is the probability that bacteria would get resistant to combination therapy? Suppose that the treatment is given ten times, what is the probability a resistant strain will develop anytime between first and tenth treatment? Explain your reasoning.
Cystic fibrosis infection and biofilm busters
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Jennifer Fiegel, Sachin Gharse
Bacteriophages (or phages) are viruses that infect bacteria, where they replicate to a high density and burst the bacterial cell (a process called amplification). Phage therapy represents a potential alterative treatment as antibiotic-resistant bacteria and biofilms do not present a challenge to phage (83). Pearl et al. (2008) demonstrated that phages remain alive within persister cells, then replicate when the persisters become active (66). Phages diffuse readily through biofilm matrices (67), expressing depolymerizing enzymes that degrade biofilm matrices and/or inducing the bacteria to express enzymes to further biofilm degradation (52,84). In mice with chronic P. aeruginosa infections, treatment with phages 24 or 48 hours post-infection resulted in complete clearance of P. aeruginosa from the lungs. After 6 days of infection, complete clearance was observed in 70% of the mice, with significant reduction in bacterial load in the remaining animals (68).
Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Matic Proj, Martina Hrast, Gregor Bajc, Rok Frlan, Anže Meden, Matej Butala, Stanislav Gobec
Infections caused by antibiotic-resistant bacteria pose a serious challenge to healthcare systems worldwide. The increasing resistance of gram-positive and gram-negative pathogens causing infections in hospitals and in the general population and the worldwide spread of antibiotic-resistant 'superbugs’ represent a major global health problem1. Reportedly, 25,000 Europeans die each year as a direct result of infections with multidrug-resistant strains of pathogenic bacteria, with an estimated economic impact of 1.5€ billion per year2. However, the pipeline for new drugs is small because major pharmaceutical companies have largely abandoned antibiotic research, despite the urgent need for new drugs3. The fact that few new antimicrobials are available and multidrug resistance is becoming more common means that we need to increase our efforts in finding new antimicrobials4. It is imperative that we continue to search for new antibacterial agents by using innovative screening methods for carefully selected protein targets and by conducting rational drug design using the advances offered by protein crystal structures.
Reverse engineering approach: a step towards a new era of vaccinology with special reference to Salmonella
Published in Expert Review of Vaccines, 2022
Shania Vij, Reena Thakur, Praveen Rishi
The benefits provided by the clinical implementation of vaccines to prevent infections caused by antibiotic-resistant bacteria are indispensable (Figure 1). Upon exposure, vaccination leads to the neutralization of the pathogen, sometimes even before the development of clinical symptoms. On the contrary, antimicrobial therapy is prescribed after the onset of clinical symptoms. Thus, vaccination could bring down the economic burden on the healthcare systems posed by diagnosis followed by treatment of antibiotic-resistant infections significantly [22]. Additionally, vaccines play a crucial role in curbing the emergence and dissemination of antimicrobial resistance by several pathways. For instance, vaccination prevents the establishment of infection by antibiotic-resistant strains because of the generation of herd immunity. In addition to reducing the possibility of selection of antibiotic-resistant strains in the clinical as well as environmental settings, vaccination also averts the establishment of sensitive strains which require antimicrobial therapy, hence taking care of the selection pressure posed by antibiotics. Moreover, vaccination can also reduce the selective pressure mediated by antibiotic therapy on commensal bacteria such as gut microbiota, which also has been suggested as the reservoir of antibiotic resistance determinants [23].
Recent advancements in cellulose-based biomaterials for management of infected wounds
Published in Expert Opinion on Drug Delivery, 2021
Munira Momin, Varsha Mishra, Sankalp Gharat, Abdelwahab Omri
Antibiotic-resistance is a serious issue that requires immediate attention. It has become a major cause of morbidity and mortality worldwide. Antibiotic-resistant bacteria have emerged as a result of improper use of antibiotics. Some bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have developed resistance to multiple antibiotics, and are referred to as multi-drug resistant bacteria. Antibiotics have been used for treating and preventing diseases in humans and animals for many years. The threat here is excessive use of antibiotics in humans, which leads to the emergence of antibiotic-resistant organisms. Furthermore, prior use of antimicrobial drugs puts a patient at risk of infection with a drug-resistant organism, and patients who have had the most antimicrobial exposure are more susceptible to infection with resistant bacteria [29–31].