The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.

Experimental Identification of Cross-Reacting IgG Hotspots to Predict Existing Immunity Evasion of SARS-CoV-2 Variants by a New Biotechnological Application of Phage Display.

Multiple pathogens are competing against the human immune response, leading to outbreaks that are increasingly difficult to control. For example, the SARS-CoV-2 virus continually evolves, giving rise to new variants. The ability to evade the immune system is a crucial factor contributing to the spread of these variants within the human population.

Interaction of Bacteriophages with the Immune System: Induction of Bacteriophage-Specific Antibodies.

In all cases when a bacteriophage makes a direct contact with a mammalian organism, it may challenge the mammalian immunological system. Its major consequence is the production of antibodies specific to the bacteriophage, particularly IgM, IgG, and IgA as the typical response. Here we present protocols applicable in studies of the ability of bacteriophage to induce specific antibodies; immunization to whole virions or to isolated phage proteins has been included.

Immunogenic epitope scanning in bacteriolytic enzymes Pal and Cpl-1 and engineering Pal to escape antibody responses.

Bacteriolytic enzymes are promising antibacterial agents, but they can cause a typical immune response . In this study, we used a targeted modification method for two antibacterial endolysins, Pal and Cpl-1. We identified the key immunogenic amino acids, and designed and tested new, bacteriolytic variants with altered immunogenicity.

Evolution of the T4 phage virion is driven by selection pressure from non-bacterial factors.

Bacteriophages colonize animal and human bodies, propagating on sensitive bacteria that are symbionts, commensals, or pathogens of animals and humans. T4-like phages are dependent on abundant symbionts such as , commonly present in animal and human gastrointestinal (GI) tracts. Bacteriophage T4 is one of the most complex viruses, and its intricate structure, particularly the capsid head protecting the phage genome, likely contributes substantially to the overall phage fitness in diverse environments.

New Phage-Derived Antibacterial Enzyme PolaR Targeting spp.

is an opportunistic pathogen, particularly life-threatening for the immunocompromised. It is associated with pneumonia, endocarditis, peritonitis and many other serious infections, including septicemia. Of note, produces metabolites that support and increase overgrowth of , one of the ESKAPE bacteria.

Assessment of Clinical Indicators Registered on Admission to the Hospital Related to Mortality Risk in Cancer Patients with COVID-19.

Background: Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system.

Biological Properties of 12 Newly Isolated -Specific Bacteriophages.

Infections with the opportunistic Gram-negative bacterium pose a serious threat today, which is aggravated by the growing problem of multi-drug resistance among bacteria, caused by the overuse of antibiotics. Treatment of infections caused by antibiotic-resistant strains with the use of phage therapy is not only a promising alternative, but sometimes the only option. Therefore, phages specific for clinical multi-drug resistant were searched for in environmental, municipal, and hospital wastewater samples collected from different locations in Poland.

Correlation between COVID-19 severity and previous exposure of patients to Borrelia spp.

Predictors for the risk of severe COVID-19 are crucial for patient care and control of the disease. Other infectious diseases as potential comorbidities in SARS-CoV-2 infection are still poorly understood. Here we identify association between the course of COVID-19 and Lyme disease (borreliosis), caused by Borrelia burgdorferi transmitted to humans by ticks.

Dynamics of anti-SARS-CoV-2 seroconversion in individual patients and at the population level.

The immune response and specific antibody production in COVID-19 are among the key factors that determine both prognostics for individual patients and the global perspective for controlling the pandemics. So called "dark figure", that is, a part of population that has been infected but not registered by the health care system, make it difficult to estimate herd immunity and to predict pandemic trajectories. Here we present a follow up study of population screening for hidden herd immunity to SARS-CoV-2 in individuals who had never been positively diagnosed against SARS-CoV-2; the first screening was in May 2021, and the follow up in December 2021.

Two Newly Isolated -Specific Bacteriophages: Biological Properties and Stability Studies.

In an era of antibiotic therapy crisis caused by spreading antimicrobial resistance, and when recurrent urinary tract infections constitute a serious social and medical problem, the isolation and complex characterization of phages with a potential therapeutic application represents a promising solution. It is an inevitable, and even a necessary direction in the development of current phage research. In this paper, we present two newly isolated myoviruses that show lytic activity against multidrug-resistant clinical isolates of spp.

Immunogenicity of Endolysin PlyC.

Endolysins are bacteriolytic enzymes derived from bacteriophages. They represent an alternative to antibiotics, since they are not susceptible to conventional antimicrobial resistance mechanisms. Since non-human proteins are efficient inducers of specific immune responses, including the IgG response or the development of an allergic response mediated by IgE, we evaluated the general immunogenicity of the highly active antibacterial enzyme, PlyC, in a human population and in a mouse model.

Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021.

Population immunity (herd immunity) to SARS-CoV-2 derives from two sources: vaccinations or cases of infection with the virus. Infections can be diagnosed as COVID-19 and registered, or they can be asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered when patients recovered at home. Estimation of population immunity to SARS-CoV-2 is difficult and remains a subject of speculations.

Endocytosis of Bacteriophages.

Endocytosis is used by eukaryotic cells for ingesting external objects. Importantly, endocytosis is a major process that determines phage pharmacokinetics in vivo. Either dissemination of phages throughout the system or phage clearance engages cellular uptake of phage particles.

Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients' medical, epidemiological and diagnostic data, virus-neutralizing capability and kinetics. N-specific IgG and IgA are the most reliable diagnostic targets for infection.

DNA Dye Sytox Green in Detection of Bacteriolytic Activity: High Speed, Precision and Sensitivity Demonstrated With Endolysins.

Increasing number of deaths from multi-drug resistant bacterial infections has caused both the World Health Organization and the Centers for Disease Control and Prevention to repeatedly call for development of new, non-traditional antibacterial treatments. Antimicrobial enzymes, including those derived from bacteriophages, known as endolysins or enzybiotics, are considered promising solutions among the emerging therapies. These naturally occurring proteins specifically destroy bacterial cell walls (peptidoglycan) and as such, are capable of killing several logs of bacteria within minutes.

Immune Response to Therapeutic Staphylococcal Bacteriophages in Mammals: Kinetics of Induction, Immunogenic Structural Proteins, Natural and Induced Antibodies.

Bacteriophages are able to affect the human immune system. Phage-specific antibodies are considered as major factors shaping phage pharmacokinetics and bioavailability. So far, general knowledge of phage antigenicity nevertheless remains extremely limited.

Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future.

The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable bacterial infections, necessitates the acceleration of studies on antibacterials of a new generation that could offer an alternative to antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well as antibiotic-resistant bacteria, and thus are a major subject of such studies. Their efficacy in curing bacterial infections has been demonstrated in in vivo experiments and in the clinic.

Circulation of Fluorescently Labelled Phage in a Murine Model.

Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled lytic phages as a new tool for the investigation of phage interactions with cells and tissues.

Phage-specific antibodies.

Antibodies specific to phage virions have been observed many times, both in animals and in humans. Phages induce the T-dependent type of immune response, which is fundamental for immunological memory and long retention of abilities to recognize and respond to foreign epitopes. Experimental models have shown that phage-specific antibodies can be devastating for a phage in vivo.

Endocytosis in cellular uptake of drug delivery vectors: Molecular aspects in drug development.

Drug delivery vectors are widely applied to increase drug efficacy while reducing the side effects and potential toxicity of a drug. They allow for patient-tailored therapy, dose titration, and therapeutic drug monitoring. A major part of drug delivery systems makes use of large nanocarriers: liposomes or virus-like particles (VLPs).

Phage Therapy: The Pharmacology of Antibacterial Viruses.

Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations.

Natural and Induced Antibodies Against Phages in Humans: Induction Kinetics and Immunogenicity for Structural Proteins of PB1-Related Phages.

Bacteriophages may induce specific antibodies after natural exposure to phages or after phage therapy. As such, phage-specific antibodies might impact phage bioavailability , although limited non-neutralizing or insignificant effects have also been reported. Here, we report antibody induction against PB1-related phages ( viruses LMA2, F8, DP1) in mice over an 80-day period, for a healthy population of humans, and in patients undergoing phage therapy (oral and/or topical treatment).

Application of 16S rRNA gene sequencing in detection.

is one of the major stomach microbiome components, promoting development of inflammation and gastric cancer in humans. has a unique ability to transform into a coccoidal form which is difficult to detect by many diagnostic methods, such as urease activity detection, and even histopathological examination. Here we present a comparison of three methods for identification: histological assessment (with eosin, hematoxylin, and Giemsa staining), polymerase chain reaction (PCR) detection of urease (ureA specific primers), and detection by 16S rRNA gene sequencing.