Biology subjects

Samuel, B.

Publications and source records attributed to Samuel, B..

5 recordsLinked to original sources

bioRxiv2026

Engineered phages evade the complete defense repertoire of highly phage-resistant MRSA clinical isolates

Phage therapy is a re-emerging approach for antimicrobial-resistant bacterial infections. However, the narrow host range of most phages remains a major barrier to the success and wider adoption of phage therapy. Although receptor incompatibility is often assumed to define phage-host specificity, we demonstrate that anti-phage defense systems are major determinants of host range in Staphylococcus aureus. Using a methicillin-resistant S. aureus (MRSA) clinical isolate as a model, we characterized the targeting profiles of its 15 defense systems and, for the first time, generated therapeutic phages that evade the full defense repertoire of a multi-phage-resistant strain. In particular, we show that defense-guided phage recombination is a powerful tool that leverages the modular design of phage genomes to replace targeted with untargeted components. Our holistic approach unveils defense synergies that constrain phage evasion and redundancies that allow the simultaneous evasion of multiple defenses. Finally, we show that an engineered phage cocktail prevents the emergence of phage resistance in the model and a second clinical strain with similar defenses. Our work provides a blueprint for translating our expanding knowledge of defense system identity and mechanism into the rational design of effective, next-generation phage therapeutics.

microbiology↗

bioRxiv2025

B-PPI: A Cross-Attention Model for Large-Scale Bacterial Protein-Protein Interaction Prediction

Protein-protein interactions (PPIs) are essential for the study of cellular function, yet computational prediction of bacterial PPIs remains limited. Most existing methods are trained on human data, reducing their applicability to bacterial systems. Here, we present B-PPI, a computational tool specifically designed for bacterial PPI prediction. B-PPI leverages embeddings from ProstT5, a structure-aware protein language model, and a cross-attention mechanism to capture residue-level inter-protein relationships. To facilitate training, we constructed B-PPI-DB, a large-scale bacterial PPI dataset derived from STRING, comprising 202,829 positive and negative interactions across 2,646 taxa with a 1:10 positive-to-negative ratio. We benchmarked B-PPI against TT3D, a state-of-the-art model trained on human PPI, which was previously evaluated on bacterial PPIs. B-PPI achieved substantially higher performance on bacterial data (AUPRC 0.926{+/-}0.006 vs. 0.230{+/-}0.005 and F1 0.866{+/-}0.007 vs. 0.299{+/-}0.005) with faster runtime. We further demonstrate that the model adapts to unseen bacterial interactions with minimal fine-tuning. Together, B-PPI and B-PPI-DB address a critical gap in computational microbiology, offering a framework for bacterial PPI prediction and a data resource for benchmarking and developing new tools in the field.

bioinformatics↗

bioRxiv2024

Identification and characterization of a skin microbiome on Caenorhabditis elegans suggests environmental microbes confer cuticle protection

In the wild, C. elegans are emersed in environments teeming with a veritable menagerie of microorganisms. The C. elegans cuticular surface serves as a barrier and first point of contact with this microbial milieux. Here, we identify microbes from C. elegans natural habitats that associate with its cuticle, constituting a simple skin microbiome. We rear our animals on a modified CeMbio, mCeMbio, a consortium of ecologically relevant microbes. We first combine standard microbiological methods with an adapted micro skin-swabbing tool to describe the skin-resident bacteria on the C. elegans surface. Further, we conduct 16S rRNA gene sequencing studies to identify relative shifts in the proportion of mCeMbio bacteria upon surface-sterilization, implying distinct skin-and gut-microbiomes. We find that some strains of bacteria, including Enterobacter sp. JUb101, are primarily found on the nematode skin, while others like Stenotrophomonas indicatrix JUb19 and Ochrobactrum vermis MYb71 are predominantly in the animals gut. Finally, we show that this skin microbiome promotes host cuticle integrity in harsh environments. Together, we identify a skin microbiome for the well-studied nematode model and propose its value in conferring host fitness advantages in naturalized contexts. ImportanceThe genetic model organism C. elegans has recently emerged as a tool for understanding host-microbiome interactions. Nearly all of these studies either focus on pathogenic or gut-resident microbes. Little is known about the existence of native, non-pathogenic skin microbes or their function. We show that members of a modified C. elegans model microbiome, mCeMbio, can adhere to the animals cuticle and confer protection from noxious environments. We combine a novel micro-swab tool, the first 16S microbial sequencing data from relatively unperturbed C. elegans, and physiological assays to demonstrate microbially mediated protection of the skin. This work serves as a foundation to explore wild C. elegans skin microbiomes and use C. elegans as a model for skin research.

microbiology↗

bioRxiv2023

A diverse repertoire of anti-defense systems is encoded in the leading region of plasmids

Plasmids are an important source of antibiotic-resistance genes that mobilize horizontally between bacteria, including many human pathogens. Bacteria express various defense mechanisms, such as CRISPR-Cas, restriction-modification systems, and SOS-response genes, to prevent the invasion of mobile elements. Yet, plasmids efficiently and robustly overcome these defenses during conjugation. Here, we show that the leading region of plasmids, which is the first to enter recipient cells, is a hotspot for an extensive repertoire of anti-defense systems, encoding anti-CRISPR, anti-restriction, anti-SOS, and other counter-defense proteins. We further demonstrate that focusing on these specific functional regions can lead to the discovery of diverse anti-defense genes. Promoters known to allow expression from ssDNA were prevalent in the leading regions, potentially facilitating rapid protection against bacterial immunity in the early stages of plasmid invasion. These findings reveal a new facet of plasmid dissemination and provide theoretical foundations for developing conjugative delivery systems for natural microbial communities.

microbiology↗

bioRxiv2021

Antimicrobial interactions between the phytoextracts of Callistemon citrinus and Eriobotrya japonica against Streptococcus mutans

Streptococcus mutans is a gram-positive bacterium in the oral cavity that is most implicated in the dental caries progression. The condition is very expensive to manage and the most commonly used products such as fluoride tooth pastes and alcohol-based mouth washes are associated with many side effects. The current study therefore focused on providing a scientific evidence to guide the use of a combination of Eriobotrya japonica (EJ) and Callistemon citrinus (CC) as actives in development of an effective and cheaper herbal formulation for management of dental caries. The objective of this study was to determine antimicrobial interactions of Eriobotrya japonica and Callistemon citrinus phytoextracts proportions against Streptococcus mutans bacteria. The leaves of both plants (EJ and CC) were shade-dried and pulverized into a coarse powder which were then cold macerated using ethanol (60 %) for 24 h. Phytochemical screening was conducted for the two dry extracts obtained after fan drying before they were mixed in to five different proportions (1:0, 3:1, 1:1, 1:3 and 0:1). Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) assays against Streptococcus mutans were done for all the proportions above with ciprofloxacin and 2.5 % Dimethyl sulfoxide (DMSO) as the positive and negative controls respectively. Antimicrobial interactions between the two extracts were also evaluated using Fractional Inhibitory and Bacterial Concentration Indices (FICI/FBCI). Results showed that EJ and CC had percentage yields of 20.05 % and 15.45 % respectively. All the extracts showed similar phytochemical profiles. They also demonstrated an inhibitory effect on Streptococcus mutans with MIC and MBC values ranging from 521 to 3333 g/ml and 1042 to 3667 g/ml respectively. However, CC: EJ (1:0) had the lowest MIC and MBC comparable to that of the standard drug at P <0.05. The FICI/FBCI were between 1.5 and 3.917. Therefore, CC: EJ (1:0) proportion markedly demonstrated better antimicrobial activity against the test organism and there are no beneficial antimicrobial interactions between the two plant extracts to inform their combination as actives for dental caries product formulation.

microbiology↗