bioRxiv Science⌕ Search

Biology subjects

Boukherroub, R.

Publications and source records attributed to Boukherroub, R..

2 recordsLinked to original sources

Breaking Through Microbial Defences - Organic Acid-Based Deep Eutectic Solvents as a Neoteric Strategy in Bacterial Biofilm, Persister, and Fungal Control

This study explores the adaptation of organic acid-based deep eutectic solvents (OA-DESs) as effective antimicrobial agents. Having already demonstrated their efficacy against planktonic bacteria in our previous research, we now investigate their impact on more complex microbial forms, including biofilms, persister cells, and fungi (both human pathogenic and phytopathogenic). Our experiments revealed that OA-DESs effectively eradicated MRSA and Escherichia coli biofilms, inducing significant morphological changes. Notably, a three-log-unit reduction was observed for most OA-DESs at concentrations below 1% v/v, a remarkable achievement for this class of materials. Additionally, with only one exception, OA-DESs did not promote persister cell formation, underscoring their potential for complete biofilm eradication. In another part of our study, OA-DESs were compared to conventional DESs against Candida albicans, Candida auris, and Aspergillus fumigatus. Results showed that while individual DES components exhibited minimal activity, their combination effectively inhibited fungal growth and induced substantial morphological changes. Lastly, OA-DESs were tested against the phytopathogens Zymoseptoria tritici and Venturia inaequalis. Though their activity was less pronounced compared to pathogenic strains, most OA-DESs inhibited the growth of both fungi at the highest tested concentrations. Despite the broad scope of this study, we believe this study provides valuable insights into the potential of DESs as antimicrobial agents, offering a strong foundation for future research and innovation in this field.

microbiology↗

nanoCLAMP potently neutralizes SARS-CoV-2 and protects K18-hACE2 mice from infection

Intranasal treatments, combined with vaccination, has the potential to slow mutational evolution of virusues by reducing transmission and replication. Here we illustrate the development of a SARS-CoV-2 receptor binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope binding nanoCLAMP, P2609. The resulting multimerised nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD (KD < 1 pM), and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC50 = 0.4 {+/-} 0.1 nM obtained from neutralization experiments using pseudoviral particles as well as patient cultured SARS-CoV-2 samples, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID19 therapeutics.

bioengineering↗