Gram-Positive Pneumonia: Possibilities Offered by Phage Therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Fernandez L
PROVIDER: S-EPMC8388979 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundAntibiotic resistance among pathogenic bacteria has created a global emergency, prompting the hunt for an alternative cure. Bacteriophages were discovered over a century ago and have proven to be a successful replacement during antibiotic treatment failure. This review discusses on the scientific investigation of phage therapy for Gram-positive pathogens and general outlook of phage therapy clinical trials and commercialization.Main body of the abstractThis review aimed to highlight the phage therapy in Gram-positive bacteria and the need for phage therapy in the future. Phage therapy to treat Gram-positive bacterial infections is in use for a very long time. However, limited review on the phage efficacy in Gram-positive bacteria exists. The natural efficiency and potency of bacteriophages against bacterial strains have been advantageous amidst the other non-antibiotic agents. The use of phages to treat oral biofilm, skin infection, and recurrent infections caused by Gram-positive bacteria has emerged as a predominant research area in recent years. In addition, the upsurge in research in the area of phage therapy for spore-forming Gram-positive bacteria has added a wealth of information to phage therapy.Short conclusionWe conclude that the need of phage as an alternative treatment is obvious in future. However, phage therapy can be used as reserve treatment. This review focuses on the potential use of phage therapy in treating Gram-positive bacterial infections, as well as their therapeutic aspects. Furthermore, we discussed the difficulties in commercializing phage drugs and their problems as a breakthrough medicine.
| S-EPMC8401357 | biostudies-literature
Project description:The phage life cycle is a multi-stage process initiated by the recognition and attachment of the virus to its bacterial host. This adsorption step depends on the specific interaction between bacterial structures acting as receptors and viral proteins called Receptor Binding Proteins (RBP). The adsorption process is essential as it is the first determinant of phage host range and a sine qua non condition for the subsequent conduct of the life cycle. In phages belonging to the Caudoviricetes class, the capsid is attached to a tail, which is the central player in the adsorption as it comprises the RBP and accessory proteins facilitating phage binding and cell wall penetration prior to genome injection. The nature of the viral proteins involved in host adhesion not only depends on the phage morphology (i.e., myovirus, siphovirus, or podovirus) but also the targeted host. Here, we give an overview of the adsorption process and compile the available information on the type of receptors that can be recognized and the viral proteins taking part in the process, with the primary focus on phages infecting Gram-positive bacteria.
| S-EPMC9863714 | biostudies-literature
Project description:The SaPIs are a cohesive subfamily of extremely common phage-inducible chromosomal islands (PICIs) that reside quiescently at specific att sites in the staphylococcal chromosome and are induced by helper phages to excise and replicate. They are usually packaged in small capsids composed of phage virion proteins, giving rise to very high transfer frequencies, which they enhance by interfering with helper phage reproduction. As the SaPIs represent a highly successful biological strategy, with many natural Staphylococcus aureus strains containing two or more, we assumed that similar elements would be widespread in the Gram-positive cocci. On the basis of resemblance to the paradigmatic SaPI genome, we have readily identified large cohesive families of similar elements in the lactococci and pneumococci/streptococci plus a few such elements in Enterococcus faecalis. Based on extensive ortholog analyses, we found that the PICI elements in the four different genera all represent distinct but parallel lineages, suggesting that they represent convergent evolution towards a highly successful lifestyle. We have characterized in depth the enterococcal element, EfCIV583, and have shown that it very closely resembles the SaPIs in functionality as well as in genome organization, setting the stage for expansion of the study of elements of this type. In summary, our findings greatly broaden the PICI family to include elements from at least three genera of cocci.
| S-EPMC5363835 | biostudies-literature
Project description:Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Despite broad literature including basic and translational scientific studies, many gaps in our understanding of host-pathogen interactions remain. In this review, pathogen virulence factors that drive lung infection and injury are discussed in relation to their associated host immune pathways. CAP epidemiology is considered, with a focus on Staphylococcus aureus and Streptococcus pneumoniae as primary pathogens. Bacterial factors involved in nasal colonization and subsequent virulence are illuminated. A particular emphasis is placed on bacterial pore-forming toxins, host cell death, and inflammasome activation. Identified host-pathogen interactions are then examined by linking pathogen factors to aberrant host response pathways in the context of acute lung injury in both primary and secondary infection. While much is known regarding bacterial virulence and host immune responses, CAP management is still limited to mostly supportive care. It is likely that improvements in therapy will be derived from combinatorial targeting of both pathogen virulence factors and host immunomodulation.
| S-EPMC6589866 | biostudies-literature
Project description:The phage-related chromosomal islands (PRCIs) were first identified in Staphylococcus aureus as highly mobile, superantigen-encoding genetic elements known as the S. aureus pathogenicity islands (SaPIs). These elements are characterized by a specific set of phage-related functions that enable them to use the phage reproduction cycle for their own transduction and inhibit phage reproduction in the process. SaPIs produce many phage-like infectious particles; their streptococcal counterparts have a role in gene regulation but may not be infectious. These elements therefore represent phage satellites or parasites, not defective phages. In this Review, we discuss the shared genetic content of PRCIs, their life cycle and their ability to be transferred across large phylogenetic distances.
| S-EPMC3522866 | biostudies-literature
Project description:In the billion years that bacteriophage (or phage) have existed together with bacteria the phage have evolved systems that may be exploited for our benefit. One of these is the lytic system used by the phage to release their progeny from an infected bacterium. Endolysins (or lysins) are highly evolved enzymes in the lytic system produced to cleave essential bonds in the bacterial cell wall peptidoglycan for progeny release. Small quantities of purified recombinant lysin added externally to gram-positive bacteria results in immediate lysis causing log-fold death of the target bacterium. Lysins have now been used successfully in a variety of animal models to control pathogenic antibiotic resistant bacteria found on mucosal surfaces and in infected tissues. The advantages over antibiotics are their specificity for the pathogen without disturbing the normal flora, the low chance of bacterial resistance, and their ability to kill colonizing pathogens on mucosal surfaces, a capacity previously unavailable. Lysins therefore, may be a much-needed anti-infective (or enzybiotic) in an age of mounting antibiotic resistance.
| S-EPMC3448103 | biostudies-literature
Project description:Surface, secreted and transmembrane protein-encoding open reading frames, collectively the secretome, can be identified in bacterial genome sequences using bioinformatics. However, functional analysis of translated secretomes is possible only if many secretome proteins are expressed and purified individually. We have now developed and applied a phage display system for direct selection, identification, expression and purification of bacterial secretome proteins.
| S-EPMC2246268 | biostudies-literature
Project description:We present the first description of a single-stranded DNA filamentous phage able to replicate in a gram-positive bacterium. Phage B5 infects Propionibacterium freudenreichii and has a genome consisting of 5,806 bases coding for 10 putative open reading frames. The organization of the genome is very similar to the organization of the genomes of filamentous phages active on gram-negative bacteria. The putative coat protein exhibits homology with the coat proteins of phages PH75 and Pf3 active on Thermus thermophilus and Pseudomonas aeruginosa, respectively. B5 is, therefore, evolutionarily related to the filamentous phages active on gram-negative bacteria.
| S-EPMC134938 | biostudies-literature
Project description:At the end of a lytic bacteriophage replication cycle in Gram-positive bacteria, peptidoglycan-degrading endolysins that cause explosive cell lysis of the host can also attack non-infected bystander cells. Here we show that in osmotically stabilized environments, Listeria monocytogenes can evade phage predation by transient conversion to a cell wall-deficient L-form state. This L-form escape is triggered by endolysins disintegrating the cell wall from without, leading to turgor-driven extrusion of wall-deficient, yet viable L-form cells. Remarkably, in the absence of phage predation, we show that L-forms can quickly revert to the walled state. These findings suggest that L-form conversion represents a population-level persistence mechanism to evade complete eradication by phage attack. Importantly, we also demonstrate phage-mediated L-form switching of the urinary tract pathogen Enterococcus faecalis in human urine, which underscores that this escape route may be widespread and has important implications for phage- and endolysin-based therapeutic interventions.
| S-EPMC9981463 | biostudies-literature
Project description:BACKGROUND:Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens. METHODS:Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7-21 days. The primary end point was clinical response at follow-up/test-of-cure visit. RESULTS:A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, -5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, -4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, -0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, -7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%). CONCLUSIONS:The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.
| S-EPMC3060890 | biostudies-literature