Biology subjects

Cohen-Cymberknoh, M.

Publications and source records attributed to Cohen-Cymberknoh, M..

2 recordsLinked to original sources

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↗

bioRxiv2020

A novel calcium-concentrating compartment drives biofilm formation and persistent infections

In nature, bacteria reside in biofilms - multicellular differentiated communities held together by extracellular matrix. In this work, we identified a novel subpopulation essential for biofilm formation - mineral-forming cells. This subpopulation contains an intracellular calcium-accumulating niche, in which the formation of a calcium carbonate mineral is initiated. As the biofilm colony develops, this mineral grows in a controlled manner, forming a functional macrostructure that serves the entire community. The molecular mechanisms promoting calcite scaffold formation were conserved between three distant phyla - the Gram-positive Bacillus subtilis, Gram-negative Pseudomonas aeruginosa and the actinobacterium Mycobacterium abscessus. Biofilm development of all three species was similarly impaired by inhibition of calcium uptake and carbonate accumulation. Moreover, chemical inhibition and mutations targeting mineralization both significantly reduced the attachment of P. aeruginosa to the lung, as well as the subsequent damage inflicted by biofilms to lung tissues, and restored their sensitivity to antibiotics. The evolutionary conserved cellular pathway controlling the fundamental feature of biofilm development uncovered in this work offers novel druggable targets for antibiotics to combat otherwise untreatable biofilm infections.

microbiology↗