Biology subjects

Livnat-Levanon, N.

Publications and source records attributed to Livnat-Levanon, N..

3 recordsLinked to original sources

bioRxiv2026

Transition Metal-Weak Organic Acid Synergy Enables Rapid Bactericidal and sporicidal Activity

The global rise in antibiotic-resistant bacteria underscores the urgent need for alternative antimicrobial strategies capable of limiting bacterial growth and viability. We previously demonstrated that weak organic acids and transition metals combine synergistically to strongly inhibit bacterial growth. Here, we extend these findings to determine whether this interaction results only in bacteriostatic suppression or can induce irreversible killing. Using standardized quantitative assays, selected acid-metal combinations achieved rapid bactericidal activity, producing >5-log reductions in Gram-negative and Gram-positive bacterial load after brief exposure at concentrations substantially lower than those required for many conventional disinfectants. This activity extended beyond vegetative cells. Bacillus cereus spores, used as a surrogate for spores of Bacillus anthracis, exhibited significant loss of viability under defined conditions. Given the environmental persistence of anthrax spores and their relevance in biological threat scenarios, these findings have implications not only for antimicrobial resistance mitigation but also for biodefense and environmental decontamination. Sporicidal efficacy was exposure dependent, with prolonged contact enabling effective killing at reduced concentrations. Together, these results establish acid-metal systems as scalable antimicrobial agents with bactericidal and sporicidal activity relevant to public health and global security. Importance statementAntibiotic resistance and the persistence of bacterial spores demand new antimicrobial strategies that are both effective and practical. This study shows that combining weak organic acids with transition metals transforms two modest antimicrobial agents into a powerful broad-spectrum killing system. These synergistic formulations rapidly eradicate Gram-negative and Gram-positive bacteria, achieving bactericidal activity at concentrations substantially lower than those used in many conventional disinfectants. Importantly, their activity extends to bacterial spores, among the most resilient biological structures known and a major challenge in environmental decontamination and biodefense. Using Bacillus cereus as a surrogate for Bacillus anthracis, we demonstrate dramatic sporicidal activity, reducing spore viability by up to six orders of magnitude. By coupling strong efficacy with a simple, scalable, and potentially environmentally compatible formulation, this work establishes transition metal-organic acid combinations as a promising new platform for infection control, environmental decontamination, and biodefense preparedness.

microbiology↗

bioRxiv2025

Prokaryotic mechanosensitive channels mediate copper influx

Copper is an essential micronutrient in all kingdoms of life, requiring a meticulous balance between acquisition and toxic overload. While copper import in eukaryotes has been investigated extensively, few prokaryotic copper importers have been identified, leading to the notion that cytoplasmic copper uptake is unnecessary in prokaryotes. Here we report that mechanosensitive channels are key players in prokaryotic copper import. Deletion of the gene encoding the E. coli small mechanosensitive channel, EcMscS, leads to significantly reduced copper influx. Conversely, overexpression of EcMscS leads to increased copper influx, elevated intracellular copper content, and renders cells hypersensitive to copper. Furthermore, specific channel blockers and competing permeating ions inhibit EcMscS copper conductance, lowering intracellular copper accumulation and alleviating copper hypersensitivity. These findings extend beyond E. coli, as other prokaryotic small mechanosensitive channels of bacterial and archaeal origin also facilitate copper influx. Taken together, these results uncover a previously unknown moonlighting function for mechanosensitive channels as a pathway for prokaryotic copper uptake.

microbiology↗

bioRxiv2023

Computational analysis of long-range allosteric communications in CFTR

Malfunction of the CFTR protein results in cystic fibrosis, one of the most common hereditary diseases. CFTR functions as an anion channel, the gating of which is controlled by long- range allosteric communications. Allostery also has direct bearings on CF treatment: the most effective CFTR drugs modulate its activity allosterically. Herein, we integrated Gaussian Network Model, Transfer Entropy, and Anisotropic Normal Mode-Langevin dynamics and investigated the allosteric communications network of CFTR. The results are in remarkable agreement with experimental observations and mutational analysis and provide extensive novel insight. We identified residues that serve as pivotal allosteric sources and transducers, many of which correspond to disease causing mutations. We find that in the ATP-free form, dynamic fluctuations of the residues that comprise the ATP binding sites facilitate the initial binding of the nucleotide. Subsequent binding of ATP then brings to the fore and focuses dynamic fluctuations that were present in a latent and diffuse form in the absence of ATP. We demonstrate that drugs that potentiate CFTRs conductance do so not by directly acting on the gating residues, but rather by mimicking the allosteric signal sent by the ATP binding sites. We have also uncovered a previously undiscovered allosteric "hotspot" located proximal to the docking site of the phosphorylated Regulatory (R) domain, thereby establishing a molecular foundation for its phosphorylation- dependent excitatory role. This study unveils the molecular underpinnings of allosteric connectivity within CFTR and highlights a novel allosteric "hotspot" that could serve as a promising target for the development of novel therapeutic interventions.

biophysics↗