Antibiotic resistance, where disease-causing microorganisms evolve to survive treatments that once killed them, is a global public health concern. The overuse of antimicrobial agents in humans, livestock, and industrial agriculture is the main driver of this resistance. So harnessing big data helps scientists home in on new antimicrobials.
| Date | July 16, 2024 |
| Source | eLife |
| Summary | Researchers have developed a method to identify new antimicrobial drugs with therapeutic potential from bacterial datasets, offering clues for discovering alternatives to traditional antibiotics. |
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Why This Study is Important
The study, published on 16th July, 2024 as a Reviewed Preprint in eLife, introduces a valuable new strategy for identifying novel lysins (enzymes produced by phages during infection) with antimicrobial activity. According to the editors, the evidence supporting the therapeutic potential of two lysins discovered in the study, PHAb10(Phage Antibiotic10) and PHAb11(Phage Antibiotic11), is robust. These findings will be of general interest to microbiologists for further exploration.
Role of Lysine
- Lysins, derived from phages(viruses that infect and replicate within bacteria) have antimicrobial effects and are considered promising alternatives to antibiotics due to their low risk of resistance and unique mechanisms.
- Recent studies have linked lysins’ antimicrobial activity to their internal peptides, short chains of up to 50 amino acids with antimicrobial peptide-like architecture.
- This led researchers to scan bacterial proteomes—entire sets of proteins expressed by bacterial genomes—rather than genomes themselves, to identify new lysins with antimicrobial activity.
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Experiment of harnessing big data helps scientists home in on new antimicrobials
- Using P307, a well-documented antimicrobial peptide, as a template, the team searched the proteome database for the bacterium Acinetobacter baumannii (A. baumannii), publicly available from the National Center for Biotechnology Information.
- They discovered five new lysins with antimicrobial potential: PHAb7-11, with PHAb10 and PHAb11 showing the most promise. To evaluate their antimicrobial activity, the team chemically synthesized their gene-coding sequences and expressed them in Escherichia coli (E. coli) cells.
- They then tested their activity against three species of bacteria: A. baumannii, P. aeruginosa, and E. coli, finding that even at low concentrations, the lysins had high antibacterial activity.
- Further tests showed PHAb10 and PHAb11 maintained robust antibacterial activity against six different cultures of bacteria in both stationary and exponential phases, regardless of antibiotic resistance.
- Additionally, PHAb10 and PHAb11 retained significant antibacterial activity after heat treatment at 100°C for one hour, unlike PHAb7, PHAb8, and PHAb9.
- X-ray crystallography revealed that PHAb10 underwent a folding-refolding process during heat treatment, stabilizing under heat stress and returning to dimeric units when cooling.
- Finally, the team tested PHAb10 in two mouse models of bacterial infection, finding that it safely and efficiently cleared the infection, demonstrating its therapeutic potential.
Aim of This Study
The eLife’s reviewers emphasized the need for further tests to enhance the robustness of the findings, such as a live/dead assay to differentiate between live and dead bacterial cells, providing greater insight into the lysins’ efficacy.
Future of This Study
Researchers’ work show that daily updated big data, such as bacterial genomes and proteomes, can be crucial in the fight against antibiotic resistance.
They successfully identified new antimicrobial lysins with therapeutic promise using our screening strategy. PHAb10 and PHAb11 are highly thermostable lysins with broad-spectrum antimicrobial action. If future studies validate this findings, these lysins could be explored further as potential therapeutic treatments.
FAQ on harnessing big data helps scientists home in on new antimicrobials
1. What are lysins?
Lysins are enzymes produced by bacteriophages (viruses that infect bacteria) during infection. They degrade the bacterial cell wall, leading to cell lysis and death. Lysins are gaining attention as potential alternatives to traditional antibiotics due to their unique mode of action and low risk of resistance development.
2. How do lysins work?
Lysins target and break down the peptidoglycan layer of bacterial cell walls, causing the bacterial cell to burst and die. This action is highly specific, meaning lysins can be tailored to target specific types of bacteria without affecting beneficial microorganisms.