Biology subjects

Rudich, Y.

Publications and source records attributed to Rudich, Y..

6 recordsLinked to original sources

bioRxiv2024

Metagenomic co-assembly reveals mobile antibiotic resistance genes in airborne microbiomes in the Eastern Mediterranean

Antibiotic resistance is a significant threat to global ecological health. Mobile resistance genes are of particular concern due to their ability to transfer between organisms. In environmental settings and within the microbiota of humans and animals, these genes can sometime move into pathogens, promoting the spread of resistance. While various dispersal mechanisms have been studied, the role of air masses and dust storms in spreading antibiotic resistance genes globally remains largely unexplored. We analyzed air samples from non-dusty conditions and Middle Eastern dust storms using a metagenomic co-assembly approach to identify mobile antibiotic resistance genes dispersed by these air masses. Our analysis shows that co-assembling low-biomass air samples of similar origin produces longer genome fragments, allowing for a more detailed bioinformatic analysis that links functional features to specific taxa. Through this method, we identified genes associated with resistance to antibiotics such as aminoglycosides, beta-lactams, bleomycin, fosfomycin, chloramphenicol, daunorubicin, fluoroquinolones, glycopeptides, quinolones, streptomycin, and tetracyclines. Approximately 10% of these genes were linked to mobile genetic elements. These findings demonstrate the potential for global spread of resistance genes across ecosystems via air masses, particularly dust storms, and underscore the need for continuous atmospheric monitoring and further research to develop strategies that mitigate their impact on public health, the environment, and agriculture.

microbiology↗

bioRxiv2024

Dust storm-driven dispersal of potential pathogens and antimicrobial resistance genes in the Eastern Mediterranean

The atmosphere hosts a microbiome that connects distant ecosystems yet remains relatively unexplored. In this study, we tested the hypothesis that dust storms enhance the spread of pathogenic microorganisms and whether these microorganisms carry antibiotic resistance and virulence-related genes in the Eastern Mediterranean. We collected air samples during a seasonal transition period, capturing data from 13 dusty days originating from Middle Eastern sources and 32 clear days, with temperatures ranging from 16.5 to 27.1 {degrees}C. Using metagenomic analysis, we identified several facultative pathogens like Klebsiella pneumoniae, Stenotrophomonas maltophilia, and Aspergillus fumigatus, which are linked to human respiratory diseases, and others like Zymoseptoria tritici, Fusarium poae, and Puccinia striiformis, which are harmful to wheat. The abundance of these pathogens increased during dust storms and with rising temperatures. Although we did not find strong evidence that these species harbored antibiotic resistance or virulence-related genes, which could be linked to their pathogenic potential, dust storms transported up to 125 times more total antibiotic resistance genes, as measured by RPKM abundance, compared to clear conditions. These levels during dust storms far exceeded those found in other ecosystems. While further research is needed to determine whether dust storms and temperature variations pose an immediate threat to public health and the environment, our findings underscore the importance of continuous monitoring of atmospheric microbiomes. This surveillance is crucial for assessing potential risks to human health and ecosystem stability, particularly in the face of accelerating global climate change.

ecology↗

bioRxiv2023

Highly conserved, positively charged tandem repeats mediate multimerization of ice nucleation proteins

In nature, frost can form at a few degrees below 0 {degrees}C. However, this process requires the assembly of tens of thousands of ice-like water molecules that align together to initiate freezing at these relatively high temperatures. Water ordering on this scale is mediated by the ice nucleation proteins of common environmental bacteria like Pseudomonas syringae and P. borealis. However, individually, these 100-kDa proteins are too small to organize enough water molecules for frost formation, and it is not known how giant, megadalton-sized multimers, which are crucial for ice nucleation at high sub-zero temperatures, form. The ability of multimers to self-assemble was suggested when the transfer of an ice nucleation protein gene into Escherichia coli led to efficient ice nucleation. Here we demonstrate that a positively-charged sub-domain at the C-terminal end of the central beta-solenoid of the ice nucleation protein is crucial for multimerization. Truncation, relocation, or change of the charge of this subdomain caused a catastrophic loss of ice nucleation ability. Cryo-electron tomography of the recombinant E. coli showed that the ice nucleation protein multimers form fibres that are [~] 5 nm across and up to 200 nm long. A model of these fibres as an overlapping series of antiparallel dimers can account for all their known properties and suggests a route to making cell-free ice nucleators for biotechnological applications.

biochemistry↗

bioRxiv2023

RBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways

SARS-CoV-2 has the capacity to evolve mutations to escape vaccine-and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool. Here, we challenged rhesus macaques with SARS-CoV-2 Delta and simultaneously treated them with aerosolized RBD-62, a protein developed through multiple rounds of in vitro evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment gave equivalent protection in upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 did not block the development of memory responses to Delta and did not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.

immunology↗

bioRxiv2022

Structure and Protein-Protein Interactions of Ice Nucleation Proteins Drive Their Activity

ABSTRACTMicrobially-produced ice nucleating proteins (INpro) are unique molecular structures with the highest known catalytic efficiency for ice formation. Their critical role in rain formation and frost damage of crops together with their diverse commercial applications warrant an in-depth under-standing of their inherent ice nucleation mechanism. We used the machine-learning based software Al-phaFold to develop the first ab initio structural model of a bacterial INpro which is a novel beta-helix structure consisting of repeated stacks of two beta strands connected by two sharp turns. Using the synchrotron radiation circular dichroism, we validated the {beta}-strand content of the model. Combining functional studies of purified recombinant INpro, electron microscopy and modeling, we further demonstrate that the formation of dimers and higher-order oligomers is key to INpro activity. This work presents a major advance in understanding the molecular foundation for bacterial ice-nucleation activity and the basis for investigating the mechanistic role of INpro-induced ice formation in the atmosphere, and for commercial design and production of ice-nucleating particles for industrial applications.

microbiology↗

bioRxiv2021

Airborne bacteria over oceans shed light on global biogeodiversity patterns

Microbes are ubiquitous in the oceans and the atmosphere, playing essential roles in biogeochemical processes. The bio-exchanges between the two environments can provide important insights into microbial distribution and diversity but are still not well understood. We simultaneously surveyed the genomic diversity of airborne and marine bacterial communities across 15 000 kilometers in the Atlantic and Pacific oceans. Higher variability of microbial community composition was observed in the atmosphere than in the ocean surface waters. In addition, a greater similarity was observed between oceans than their overlaying atmosphere, and between atmospheric samples than with the ocean beneath. We additionally detected a higher coverage rate and relative abundance of marine bacteria in the Pacific atmosphere as compared to the Atlantic, while the dominant fraction in the Atlantic atmosphere was annotated as soil-associated bacteria. This study advances our understanding of microbial dispersion in the ocean, the atmosphere, and the exchange between them, as well as their potential impact on microbial composition, ecology, and biogeochemistry.

ecology↗