Biology subjects

Yerushalmy, O.

Publications and source records attributed to Yerushalmy, O..

6 recordsLinked to original sources

bioRxiv2025

Towards Clinical Phage Microbiology for Biofilm Infections: A Comparative Study and a Suggested Protocol

Non-resolving bacterial infections involve biofilm formation and are often complicating treatments. Utilizing lytic bacteriophages with antibiotics holds promise in biofilm eradication. Accurately matching phage-antibiotic combinations against target bacteria, termed Clinical Phage Microbiology (CPM), is crucial in effective phage therapy treatments. However, compared to planktonic cultures, performing CPM on biofilm infections poses a significant challenge due to the lack of effective methods and a standard protocol. This study compared various CPM approaches in biofilms. To this end, the activity of five phages was assessed against Pseudomonas aeruginosa biofilms using nine methods and multiple approaches. Here, we discuss various aspects of each technique, including sensitivity, duration, ease of implementation in diagnostic labs, and labor. Finally, we offer a preliminary protocol for testing phage-sensitivity in biofilm, which was tested on various bacteria species, and may serve as a basis for comprehensive CPM in biofilm.

microbiology↗

bioRxiv2024

Complete Genome Sequence of Six Pseudomonas aeruginosa Bacteriophages aim for research and treatments

IntroductionPseudomonas aeruginosa is a major opportunistic pathogen associated with healthcare-associated infections. The rise of antibiotic-resistant strains necessitates alternative treatment strategies, with bacteriophage therapy being a promising approach. MethodsSix bacteriophages were isolated from sewage samples. Phage isolation involved centrifugation, filtration, and plaque assays. The morphology of each was examined using Transmission Electron Microscopy (TEM). Genomic DNA was sequenced analyzed and compared. Phages lytic activity was assessed using growth curve analysis. ResultsThe six phages displayed distinct genomic and morphological characteristics, in three genomic clusters. No known virulence or antibiotic resistance genes were detected, indicating their safety for therapeutic use. TEM analysis revealed diverse morphologies, with some phages belonging to the Siphoviridae family and others to the Myoviridae family. Lysogenic phages demonstrated less effective lytic activity. ConclusionSome of these phages are promising candidates for the research of phage therapy efficacy, and the lytic phages can be used against P. aeruginosa infections.

microbiology↗

bioRxiv2024

Pulsed blue light and phage therapy: A novel synergistic bactericide

Antibiotic-resistant Pseudomonas aeruginosa (PA) is a critical health threat. Novel treatment approaches are urgently required in this post-antibiotic era. In the current study, we investigated the bactericidal combinatorial potential of two non-antibiotic alternative approaches: phage therapy and pulsed blue light (PBL). Bacteriophages (phages), are viruses that specifically infect and lyse bacteria without harming eukaryotic cells. Pulsed blue light (PBL) alters bacterial membranes and was clinically shown to be innocuous to the skin in low doses. Here, using a low dose 457nm, 33KHz PBL combined with specific PA targeting phages, we demonstrated a synergistic effect that achieved complete inhibition of planktonic bacteria and a 40% reduction in formed biofilms. As part of this study, we also developed a user-friendly python-based tool for extraction of growth curve outcomes. In vivo studies are warranted for further validation of this combinatorial treatment. This approach may lead to a novel, antibiotic complementary modality to help patients suffering from difficult-to-treat antibiotic-resistant infections. One Sentence SummaryLow-dose pulsed blue light and phage therapy have a synergistic bactericidal effect on Pseudomonas aeruginosa planktonic cultures and formed biofilm

microbiology↗

bioRxiv2021

Expanding Clinical Phage Microbiology:‎Simulating Phage Inhalation for Respiratory Tract Infections ‎

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target CF-common pathogens, were aerosolized and administered to a real-scale CT{square}derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success. Take-Home MessagePhage therapy can be used against infectious diseases if personally tailored. Using a 3D airways model, we show that phage delivery by inhalation to the respiratory tract is unpredictable and also requires a precise evaluation.

microbiology↗

bioRxiv2021

Targeting Biofilm of MDR Providencia stuartii by Phages Using a Catheter Model

Providencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and lysogenic bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.

microbiology↗

bioRxiv2021

Clinical Phage Microbiology:A suggested framework and recommendations for the in-vitro matching steps ‎of phage therapy

Personalized-phage-therapy is a promising solution for the emerging crisis of bacterial infections that fail to be eradicated by conventional antibiotics. One of the most crucial elements of personalized-phage-therapy is the proper matching of phages and antibiotics to the target bacteria in a given clinical setting. However, to date, there is no consensus guideline for laboratory procedures that enable in vitro evaluation of phages intended for treatment. In this work, we suggest a framework and strategies identify appropriate phages and combine them with antibiotics in clinical microbiology laboratories. This framework, which we term here "Clinical Phage Microbiology" is based on our experience and other previously reported cases of both, successful and failed phage treatments. Additionally, we discuss troubleshooting methodologies for possible pitfalls and special cases that may need to be assessed before treatment including interactions with the host immune system, biofilms, and polymicrobial infections. We believe that the "Clinical Phage Microbiology" pipeline presented here should serve as the basis for standardization of laboratory protocols to match phages for personalized therapy.

microbiology↗