In situ generation of cold atmospheric plasma-activated mist and its biocidal activity against surrogate viruses for COVID-19.

AIMS: To provide an alternative to ultra violet light and vapourized hydrogen peroxide to enhance decontamination of surfaces as part of the response to the COVID-19 pandemic. METHODS AND RESULTS: We developed an indirect method for in situ delivery of cold plasma and evaluated the anti-viral activity of plasma-activated mist (PAM) using bacteriophages phi6, MS2, and phiX174, surrogates for SARS-CoV-2. Exposure to ambient air atmospheric pressure derived PAM caused a 1.71 log10 PFU ml-1 reduction in phi6 titer within 5 min and a 7.4 log10 PFU ml-1 reduction after 10 min when the the PAM source was at 5 and 10 cm. With MS2 and phiX174, a 3.1 and 1.26 log10 PFU ml-1 reduction was achieved, respectively, after 30 min. The rate of killing was increased with longer exposure times but decreased when the PAM source was further away. Trace amounts of reactive species, hydrogen peroxide and nitrite were produced in the PAM, and the anti-viral activity was probably attributable to these and their secondary reactive species. CONCLUSIONS: PAM exhibits virucidal activity against surrogate viruses for COVID-19, which is time and distance from the plasma source dependent.

Antiviral Activity of Peptide-Based Assemblies.

The COVID-19 pandemic highlighted the importance of developing surfaces and coatings with antiviral activity. Here, we present, for the first time, peptide-based assemblies that can kill viruses. The minimal inhibitory concentration (MIC) of the assemblies is in the range tens of micrograms per milliliter. This value is 2 orders of magnitude smaller than the MIC of metal nanoparticles. When applied on a surface, by drop casting, the peptide spherical assemblies adhere to the surface and form an antiviral coating against both RNA- and DNA-based viruses including coronavirus. Our results show that the coating reduced the number of T4 bacteriophages (DNA-based virus) by 3 log, compared with an untreated surface and 6 log, when compared with a stock solution. Importantly, we showed that this coating completely inactivated canine coronavirus (RNA-based virus). This peptide-based coating can be useful wherever sterile surfaces are needed to reduce the risk of viral transmission.

Viruses with U-DNA: New Avenues for Biotechnology.

Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA-protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.

An automated room disinfection system using ozone is highly active against surrogates for SARS-CoV-2.

BACKGROUND: The presence of coronaviruses on surfaces in the patient environment is a potential source of indirect transmission. Manual cleaning and disinfection measures do not always achieve sufficient removal of surface contamination. This increases the importance of automated solutions in the context of final disinfection of rooms in the hospital setting. Ozone is a highly effective disinfectant which, combined with high humidity, is an effective agent against respiratory viruses. Current devices allow continuous nebulization for high room humidity as well as ozone production without any consumables. AIM: In the following study, the effectiveness of a fully automatic room decontamination system based on ozone was tested against bacteriophage Φ6 (phi 6) and bovine coronavirus L9, as surrogate viruses for the pandemic coronavirus SARS-CoV-2. METHODS: For this purpose, various surfaces (ceramic tile, stainless steel surface and furniture board) were soiled with the surrogate viruses and placed at two different levels in a gas-tight test room. After using the automatic decontamination device according to the manufacturer's instructions, the surrogate viruses were recovered from the surfaces and examined by quantitative cultures. Then, reduction factors were calculated. FINDINGS: The ozone-based room decontamination device achieved virucidal efficacy (reduction factor >4 log10) against both surrogate organisms regardless of the different surfaces and positions confirming a high activity under the used conditions. CONCLUSION: Ozone is highly active against SARS-CoV-2 surrogate organisms. Further investigations are necessary for a safe application and efficacy in practice as well as integration into routine processes.

A Comparison of Porphyrin Photosensitizers in Photodynamic Inactivation of RNA and DNA Bacteriophages.

Effective broad-spectrum antiviral treatments are in dire need as disinfectants and therapeutic alternatives. One such method of disinfection is photodynamic inactivation, which involves the production of reactive oxygen species from dissolved oxygen in response to light-stimulated photosensitizers. This study evaluated the efficacy of functionalized porphyrin compounds for photodynamic inactivation of bacteriophages as human virus surrogates. A blue-light light emitting diode (LED) lamp was used to activate porphyrin compounds in aqueous solution (phosphate buffer). The DNA bacteriophages ΦX174 and P22 were more resistant to porphyrin TMPyP photodynamic inactivation than RNA bacteriophage fr, with increasing rates of inactivation in the order: ΦX174 << P22 << fr. Bacteriophage ΦX174 was therefore considered a resistant virus suitable for the evaluation of three additional porphyrins. These porphyrins were synthesized from TMPyP by inclusion of a central palladium ion (PdT4) and/or the addition of a hydrophobic C14 chain (PdC14 or C14). While the inactivation rate of bacteriophage ΦX174 via TMPyP was similar to previous reports of resistant viruses, ΦX174 inactivation increased by a factor of approximately 2.5 using the metalloporphyrins PdT4 and PdC14. The order of porphyrin effectiveness was TMPyP < C14 < PdT4 < PdC14, indicating that both Pd2+ ligation and C14 functionalization aided virus inactivation.

Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut.

Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host. Environmental conditions can lead to prophage induction; the switching from prophage replication to lytic replication, that results in new bacteriophage progeny and the lysis of the bacterial host. Despite their abundance in the gut, little is known about what could be inducing these prophages. We show that several medications, at concentrations predicted in the gut, lead to prophage induction of bacterial isolates from the human gut. We tested five medication classes (non-steroidal anti-inflammatory, chemotherapy, mild analgesic, cardiac, and antibiotic) for antimicrobial activity against eight prophage-carrying human gut bacterial representative isolates in vitro. Seven out of eight bacteria showed signs of growth inhibition in response to at least one medication. All medications led to growth inhibition of at least one bacterial isolate. Prophage induction was confirmed in half of the treatments showing antimicrobial activity. Unlike antibiotics, host-targeted medications led to a species-specific induction of Clostridium beijerinckii, Bacteroides caccae, and to a lesser extent Bacteroides eggerthii. These results show how common medication consumption can lead to phage-mediated effects, which in turn would alter the human gut microbiome through increased prophage induction.

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment.

Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes in the human gut microbiome are often investigated in cohorts with preexisting health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologs did not significantly change, antibiotic-specific gene homologs with presumed resistance toward the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed an expansion of antibiotic-specific resistance gene homologs even 3 months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.Abbreviation: ARG - Antibiotic resistance gene homolog; AsRG - Antibiotic-specific resistance gene homolog; AZY - Azithromycin; CFX - Cefuroxime; CIP - Ciprofloxacin; DOX - Doxycycline; FDR - False discovery rate; GRiD - Growth rate index value; HGT - Horizontal gene transfer; NMDS - Non-metric multidimensional scaling; qPCR - Quantitative polymerase chain reaction; RPM - Reads per million mapped reads; TA - Transcriptional activity; TE - Transposable element; TPM - Transcripts per million mapped reads.

Antiviral application of colloidal and immobilized silver nanoparticles.

This study explored the application of colloidal and immobilized silver nanoparticles (AgNPs) for inactivation of bacteriophages. Coliphages that are commonly used as indicators for enteric viruses, were used in this study. Colloidal AgNPs were synthesized via a chemical reduction approach using sodium borohydride as reducing agent and trisodium citrate as stabilizing agent. AgNP-immobilized glass substrate was prepared by immobilizing AgNPs on amine-functionalized glass substrate by post-immobilization method. The AgNP-immobilized glass substrate was also tested so as to minimize the release of AgNPs in the treated water. The characterization of AgNPs and the AgNP-immobilized glass surface was done using field emission gun-transmission electron microscopy and scanning electron microscopy. Studies conducted with varying concentrations of colloidal AgNPs displayed good antiviral activity for MS2 and T4 bacteriophage. Colloidal AgNPs at a dose of 60 µg ml-1 could completely inactivate MS2 and T4 bacteriophage within 30 and 50 min with an initial concentration of 103 PFU ml-1. Contaminated water (100 ml) in an unstirred batch reactor with an initial bacteriophage concentration of 103 PFU ml-1 could be inactivated by the AgNP-immobilized glass substrate (1 cm × 1 cm, containing 3.7 µg cm-2 silver) suspended centrally in the batch reactor. Complete 3-Log bacteriophage inactivation was achieved within 70 and 80 min for MS2 and T4 bacteriophage, respectively, while the aqueous silver concentration was less than 25 µg l-1. This is significantly lower than the recommended standard for silver in drinking water (i.e. 100 µg l-1, US EPA). Thus, AgNP-immobilized glass may have good potential for generating virus-free drinking water.

Packaging Covered with Antiviral and Antibacterial Coatings Based on ZnO Nanoparticles Supplemented with Geraniol and Carvacrol.

The purpose of the study was to obtain an external coating based on nanoparticles of ZnO, carvacrol, and geraniol that could be active against viruses such as SARS-Co-V2. Additionally, the synergistic effect of the chosen substances in coatings was analyzed. The goal of the study was to measure the possible antibacterial activity of the coatings obtained. Testing antiviral activity with human pathogen viruses, such as SARS-Co-V2, requires immense safety measures. Bacteriophages such as phi 6 phage represent good surrogates for the study of airborne viruses. The results of the study indicated that the ZC1 and ZG1 coatings containing an increased amount of geraniol or carvacrol and a very small amount of nanoZnO were found to be active against Gram-positive and Gram-negative bacteria. It is also important that a synergistic effect between these active substances was noted. This explains why polyethylene (PE) films covered with the ZC1 or ZG1 coatings (as internal coatings) were found to be the best packaging materials to extend the quality and freshness of food products. The same coatings may be used as the external coatings with antiviral properties. The ZC1 and ZG1 coatings showed moderate activity against the phi 6 phage that has been selected as a surrogate for viruses such as coronaviruses. It can be assumed that coatings ZG1 and ZC1 will also be active against SARS-CoV-2 that is transmitted via respiratory droplets.

Comparison of microbial communities and the antibiotic resistome between prawn mono- and poly-culture systems.

Antibiotic resistance genes (ARGs) in mariculture sediments pose a potential risk to public health due to their ability to transfer from environmental bacteria to human pathogens. Long term, this may reduce pathogen susceptibility to antibiotics in medical settings. In recent years, the poly-culture of multiple species has become a popular mariculture approach in China, thanks to its environmental and economic benefits. However, differences in microbial communities and antibiotic resistome between mono- and poly-culture systems are still unclear. In this study, microbial community composition and profiles of entire (microbial DNA) and mobile (plasmid and phage) ARGs in prawn mono- and poly-culture systems were investigated using metagenomics. The abundance of several viruses and human pathogens were enhanced in prawn poly-culture ponds, when compared to monoculture systems. In contrast, sediments from poly-culture systems had a lower diversity and ARG abundance when compared to mono-culture approaches. These ARG variations were predominantly related to mobile genetic elements. Prawn mariculture activities exerted a unique selectivity for ARGs in plasmids, and this selectivity was not influenced by culture methods. The findings of this study have important implications for the selection of mariculture systems in preventing pollution with ARGs.

Phage-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.

Biochemical and Molecular Characteristics of Pc1 Virulent Phage Isolate Infecting Pectobacterium carotovorum.

BACKGROUND AND OBJECTIVE: Pectobacterium carotovorum subsp. carotovorum is a plant-pathogenic bacterium. It is a post-harvest pathogen and causes soft rot diseases in infected plants. Different virulent bacteriophages have been isolated from different regions in the world. These bacteriophages were tolerant to high concentrations of calcium chloride and magnesium chloride. Whereas, the high concentrations of zinc chloride and aluminum chloride decreased the activity and stability of phages. Therefore, the present research aimed to study the biology of P. carotovorum phage (Pc1) by using a one-step growth experiment, its stability to different concentrations of some chemicals and molecular characteristics of this phage isolate. MATERIALS AND METHODS: One step growth experiment, chemical stability, and molecular characteristics by using RAPD-PCR of P. carotovorum phage (Pc1) were studied. RESULTS: The P. carotovorum phage (Pc1) isolate was found to have a latent period of 20 min and its burst size is about 92 pfu cell-1. Calcium chloride, magnesium chloride, and copper sulphate (from 0.1-0.5 mM) increased the infectivity of Pc1 phage, while, zinc chloride in the same concentrations reduced its infectivity. RAPD-PCR amplification was indicated that the total amplified products were 32 bands with size ranged from 0.179-2.365 Kbp. CONCLUSION: Since, zinc chloride (at concentrations of 0.1-0.5 mM) reduced infectivity of Pc1 phage isolate, therefore, any chemical compounds containing zinc must be avoided in designing biocontrol strategy by using phages against soft rot bacterium (P. carotovorum) in potatoes.

Wine Phenolic Compounds Differently Affect the Host-Killing Activity of Two Lytic Bacteriophages Infecting the Lactic Acid Bacterium Oenococcus oeni.

To provide insights into phage-host interactions during winemaking, we assessed whether phenolic compounds modulate the phage predation of Oenococcus oeni. Centrifugal partition chromatography was used to fractionate the phenolic compounds of a model red wine. The ability of lytic oenophage OE33PA to kill its host was reduced in the presence of two collected fractions in which we identified five compounds. Three, namely, quercetin, myricetin and p-coumaric acid, significantly reduced the phage predation of O. oeni when provided as individual pure molecules, as also did other structurally related compounds such as cinnamic acid. Their presence was correlated with a reduced adsorption rate of phage OE33PA on its host. Strikingly, none of the identified compounds affected the killing activity of the distantly related lytic phage Vinitor162. OE33PA and Vinitor162 were shown to exhibit different entry mechanisms to penetrate into bacterial cells. We propose that ligand-receptor interactions that mediate phage adsorption to the cell surface are diverse in O. oeni and are subject to differential interference by phenolic compounds. Their presence did not induce any modifications in the cell surface as visualized by TEM. Interestingly, docking analyses suggest that quercetin and cinnamic acid may interact with the tail of OE33PA and compete with host recognition.

High-throughput mapping of the phage resistance landscape in E. coli.

Bacteriophages (phages) are critical players in the dynamics and function of microbial communities and drive processes as diverse as global biogeochemical cycles and human health. Phages tend to be predators finely tuned to attack specific hosts, even down to the strain level, which in turn defend themselves using an array of mechanisms. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. We also identify both phage-specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. Our systematic and high-throughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phage-mediated selection will shape bacterial phenotype and evolution. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering.

Detection of preQ0 deazaguanine modifications in bacteriophage CAjan DNA using Nanopore sequencing reveals same hypermodification at two distinct DNA motifs.

In the constant evolutionary battle against mobile genetic elements (MGEs), bacteria have developed several defense mechanisms, some of which target the incoming, foreign nucleic acids e.g. restriction-modification (R-M) or CRISPR-Cas systems. Some of these MGEs, including bacteriophages, have in turn evolved different strategies to evade these hurdles. It was recently shown that the siphophage CAjan and 180 other viruses use 7-deazaguanine modifications in their DNA to evade bacterial R-M systems. Among others, phage CAjan genome contains a gene coding for a DNA-modifying homolog of a tRNA-deazapurine modification enzyme, together with four 7-cyano-7-deazaguanine synthesis genes. Using the CRISPR-Cas9 genome editing tool combined with the Nanopore Sequencing (ONT) we showed that the 7-deazaguanine modification in the CAjan genome is dependent on phage-encoded genes. The modification is also site-specific and is found mainly in two separate DNA sequence contexts: GA and GGC. Homology modeling of the modifying enzyme DpdA provides insight into its probable DNA binding surface and general mode of DNA recognition.

Antiphage activity of natural and synthetic substances: a new age for antivirals?

Viruses are considered biological entities that possess a genome and can adapt to the environment of living organisms. Since they are obligate intracellular parasites, their cycle of replication can result in cell death, and consequently, some viruses are harmful to mammalian cells and can cause disease in humans. Therefore, the search for substances for the treatment of viral diseases can be accomplished through the use of bacteriophages as models for eukaryotic cell viruses. Thus, this review highlights the main studies identifying substances with antiphage activity in comparison assays involving phages and eukaryotic viruses, in order to explore the potential of these substances as antivirals. As a future perspective, this approach may help at the beginning of an Antiviral Age.

Bacteriophages, a New Therapeutic Solution for Inhibiting Multidrug-Resistant Bacteria Causing Wound Infection: Lesson from Animal Models and Clinical Trials.

Wound infection kills a large number of patients worldwide each year. Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most important colonizing pathogens of wounds that, with various virulence factors and impaired immune system, causes extensive tissue damage and nonhealing wounds. Furthermore, the septicemia caused by these pathogens increases the mortality rate due to wound infections. Because of the prevalence of antibiotic resistance in recent years, the use of antibiotics to inhibit these pathogens has been restricted, and the topical application of antibiotics in wound infections increases antibiotic resistance. Therefore, finding a new therapeutic strategy against wound infections is so essential since these infections have a destructive effect on the patient's mental health and high medical costs. In this review, we discussed the use of phages for the prevention of multidrug-resistant (MDR) bacteria, causing wound infection and their role in wound healing in animal models and clinical trials. The results showed that phages have a high ability to inhibit different wound infections caused by MDR bacteria, heal the wound faster, have lower side effects and toxicity, destroy bacterial biofilm, and they are useful in controlling immune responses. Many studies have used animal models to evaluate the function of phages, and this study appears to have a positive impact on the use of phages in clinical practice and the development of a new therapeutic approach to control wound infections, although there are still many limitations.

Searching for a Bacteriophage Lysin to Treat Corynebacterium bovis in Immunocompromised Mice.

Corynebacterium bovis is the causative agent of Corynebacterium-associated hyperkeratosis in immunocompromised mice. The resulting skin pathology can be profound and can be associated with severe wasting, making the animals unsuitable for research. Although the administration of antibiotics is effective in resolving clinical symptoms, antibiotics do not eradicate the offending bacterium. Furthermore, antibiotic use may be contraindicated as it can affect tumor growth and is associated with Clostridioides difficile enterotoxemia in highly immunocompromised murine strains. Lysins, which are lytic enzymes obtained from bacteriophages, are novel antimicrobial agents for treating bacterial diseases. The advantage of lysins are its target specificity, with minimal off-target complications that could affect the host or the biology of the engrafted tumor. The aim of this study was to identify lysins active against C. bovis. Chemical activation of latent prophages by using mitomycin C in 3 C. bovis isolates did not cause bacteriophage induction as determined through plaque assays and transmission electron microscopy. As an alternative approach, 8 lysins associated with other bacterial species, including those from the closely related species C. falsenii, were tested for their lytic action against C. bovis but were unsuccessful. These findings were congruent with the previously reported genomic analysis of 21 C. bovis isolates, which failed to reveal bacteriophage sequences by using the PHAST and PHASTER web server tools. From these results, we suggest C. bovis is among those rare bacterial species devoid of lysogenic bacteriophages, thus making the identification of C. bovis-specific lysins more challenging. However, C. bovis may be a useful model organism for studying the effects of antiphage systems.

High frequency acoustic nebulization for pulmonary delivery of antibiotic alternatives against Staphylococcus aureus.

The increasing prevalence of multidrug resistant bacteria has warranted the search for new antimicrobial agents as existing antibiotics lose their potency. Among these, bacteriophage therapy, as well as the administration of specific bacteriolysis agents, i.e., lytic enzymes, have emerged as attractive alternatives. Nebulizers offer the possibility for delivering these therapeutics directly to the lung, which is particularly advantageous as a non-invasive and direct route to treat bacterial lung infections. Nevertheless, nebulizers can often result in significant degradation of the bacteriophage or protein, both structurally and functionally, due to the large stresses the aerosolization process imposes on these entities. In this work, we assess the capability of a novel low-cost and portable hybrid surface and bulk acoustic wave platform (HYDRA) to nebulize a Myoviridae bacteriophage (phage K) and lytic enzyme (lysostaphin) that specifically targets Staphylococcus aureus. Besides its efficiency in producing phage or protein-laden aerosols within the 1-5 µm respirable range for optimum delivery to the lower respiratory tract where lung infections commonly take place, we observe that the HYDRA platform-owing to the efficiency of driving the aerosolization process at relatively low powers and high frequencies (approximately 10 MHz)-does not result in appreciable denaturation of the phages or proteins, such that the loss of antimicrobial activity following nebulization is minimized. Specifically, a low (0.1 log10 (pfu/ml)) titer loss was obtained with the phages, resulting in a high viable respirable fraction of approximately 90%. Similarly, minimal loss of antimicrobial activity was obtained with lysostaphin upon nebulization wherein its minimum inhibitory concentration (0.5 µg/ml) remained unaltered as compared with the non-nebulized control. These results therefore demonstrate the potential of the HYDRA nebulization platform as a promising strategy for pulmonary administration of alternative antimicrobial agents to antibiotics for the treatment of lung diseases caused by pathogenic bacteria.

3D printed bioceramic for phage therapy against bone nosocomial infections.

This study provides a new therapeutic response to postoperative joint and bone infections. Alone or in combination with antibiotics, phage therapy has many advantages, including accurate targeting of pathogenic bacteria. In addition, a decrease in harmful side effects can improve the healing process. Integrating the bacteriophage directly into the graft product will improve the antibacterial spread over the site of the surgery. The phage cocktail-filled ceramics are an innovative device for localized and curative phage therapy (in prosthetic replacement surgery, for example) in bone and joint surgery. Calcium phosphate-based ceramics were synthesized and shaped by stereolithography (3D) before loading by a phage cocktail to lyse a heterospecific bacterial population. In addition, the device makes possible the protection of osteoblastic cells against Staphylococcus aureus infection during their colonization on the ceramic material and prevents the formation of biofilm on the surface of biomaterials.