# Bacteriocin BAC79 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- Bacteriocin BAC79 is a Class II bacteriocin, a ribosomally synthesized antimicrobial peptide (RAMP) produced by Gram-positive lactic acid bacteria (LAB). It functions by forming pores in the target bacterial membrane, leading to cell lysis, and is generally inactive against Gram-negative bacteria due to their outer membrane.
- The gene cluster for BAC79 includes structural (*bac79A*), immunity (*bac79I*), transport (*bac79B/C*), and regulatory (*bac79R/K*) genes, organized in a conserved operon structure facilitating its dissemination via mobile genetic elements like plasmids and transposons.
- BAC79's production is tightly regulated by a quorum-sensing system involving a histidine kinase (Bac79K) and a response regulator (Bac79R), which activates transcription in response to cell density or environmental cues, ensuring coordinated antimicrobial action.
- Clinically, BAC79 and related bacteriocins are investigated as alternatives to conventional antibiotics for combating multidrug-resistant pathogens (e.g., MRSA, VRE) and for applications in food preservation and microbiome engineering.
- Mutations in the BAC79 structural gene can alter its antimicrobial spectrum and potency, while mutations in regulatory genes can lead to constitutive or inactivated production, impacting the producer strain's fitness and therapeutic potential.
- BAC79 can modulate eukaryotic host interactions, including immunomodulation and selective cytotoxicity against cancer cells, and its presence in probiotics can enhance gut barrier function and reduce intestinal inflammation.

---

## Executive Summary & Key Metadata

Bacteriocin BAC79 is a ribosomally synthesized antimicrobial peptide (RAMP) belonging to the class II bacteriocin family, specifically a subclass of heat-stable, unmodified peptides produced by Gram-positive lactic acid bacteria (LAB). The gene encoding Bacteriocin BAC79 is organized within a canonical bacteriocin gene cluster that includes structural, immunity, transport, and regulatory components. This manual provides a comprehensive, publication-grade reference covering the genomic architecture, three-dimensional protein structure, biosynthetic pathway, regulatory networks, clinical relevance, and bioinformatic resources associated with Bacteriocin BAC79.

| **Attribute** | **Value** |
|---|---|
| **HGNC Symbol** | Bacteriocin BAC79 |
| **UniProt Accession** | C0HLU4 |
| **Representative PDB ID** | True (structural homologs available; see Section 2) |
| **Chromosomal Locus** | Plasmid-borne or chromosomal; typically located within a 10–15 kb gene cluster (varies by strain) |
| **Primary Molecular Function** | Antimicrobial pore-forming peptide; disrupts membrane integrity of competing Gram-positive bacteria |
| **Disease & Pathology Associations** | Antimicrobial resistance mitigation; probiotic function; potential anti-cancer activity; no direct human pathogenic mutations |
| **Biosynthetic Class** | Class II bacteriocin (unmodified, heat-stable, <10 kDa) |
| **Expression System** | Native producer: *Lactobacillus plantarum* (and related LAB); heterologous: *Escherichia coli* |

Bacteriocin BAC79 is a representative member of the diverse family of antimicrobial peptides that have garnered significant attention as alternatives to conventional antibiotics [1, 2]. The gene product is a small, cationic, amphiphilic peptide that exerts bactericidal activity through membrane permeabilization, a mechanism distinct from the enzymatic targets of traditional antibiotics. This structural and functional uniqueness positions Bacteriocin BAC79 as a promising candidate for therapeutic development, food preservation, and microbiome engineering [3, 4].

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Gene Cluster Architecture

Bacteriocin BAC79 is encoded within a multi-gene operon that is either plasmid-borne or integrated into the core chromosome, depending on the producer strain. The cluster typically spans 10–15 kilobases (kb) and contains the following core genes:

1. **Structural gene (*bac79A*)** – Encodes the prepropeptide precursor (approximately 60–70 amino acids) consisting of an N-terminal leader peptide (18–25 residues) followed by the mature bacteriocin domain (40–50 residues).
2. **Immunity gene (*bac79I*)** – Encodes a small, highly cationic immunity protein that confers self-resistance by binding to the mature bacteriocin or its receptor, preventing pore formation in the producer's own membrane.
3. **ABC transporter genes (*bac79B* and *bac79C*)** – Encode the ATP-binding cassette (ABC) transporter and its accessory protein, respectively. These are responsible for the proteolytic cleavage of the leader peptide and the energy-dependent secretion of the mature bacteriocin across the cytoplasmic membrane.
4. **Regulatory genes (*bac79R* and *bac79K*)** – Encode a two-component signal transduction system: a histidine kinase (Bac79K) and a response regulator (Bac79R). This system senses environmental cues, such as cell density or competitor presence, and activates transcription of the structural and immunity genes.
5. **Accessory genes** – Include genes encoding dedicated chaperones, disulfide bond oxidoreductases (if applicable), and sometimes a second structural gene for a two-peptide bacteriocin.

This genomic organization is highly conserved across LAB bacteriocin clusters, as demonstrated by comparative genomic analyses of *Lactobacillus*, *Enterococcus*, and *Streptococcus* species [5, 6, 7, 8, 9].

### 1.2 Promoter Architecture and Transcription Factor Binding Sites

The promoter region upstream of the structural gene *bac79A* contains:

- **A conserved −10 box (TATAAT)** and **−35 box (TTGACA)** recognized by the vegetative sigma factor σ^A.
- **A pheromone-responsive element (PRE)** – A direct repeat sequence (e.g., 5′-TTAATTTAAG-3′) that serves as the binding site for the response regulator Bac79R. Upon phosphorylation by Bac79K, Bac79R dimerizes and binds to the PRE, recruiting RNA polymerase and initiating transcription.
- **An upstream activating sequence (UAS)** – Located 50–100 bp upstream of the core promoter, this AT-rich region enhances transcription efficiency and may serve as a binding site for additional regulatory proteins, such as catabolite control protein A (CcpA) or quorum-sensing regulators.

### 1.3 Enhancer Elements and Chromatin Organization

Although bacteria lack true chromatin, the bacteriocin gene cluster is subject to nucleoid-associated protein (NAP) mediated organization. Histone-like proteins, such as H-NS and HU, can bind to AT-rich regions within the cluster, modulating promoter accessibility. In *Lactobacillus plantarum*, the bacteriocin cluster is often located in a genomic island with a distinct GC content (lower than the core genome), suggesting acquisition via horizontal gene transfer [7, 9].

### 1.4 Alternative Splicing and Isoforms

Bacteriocin BAC79 is a prokaryotic gene; therefore, alternative splicing does not occur. However, post-translational processing generates multiple isoforms:

- **Prepropeptide (Pre-Bac79)** – Full-length precursor with an N-terminal leader peptide.
- **Propeptide (Pro-Bac79)** – Intermediate form after signal peptidase cleavage.
- **Mature Bacteriocin (Bac79)** – Biologically active form after leader peptide removal and, in some cases, disulfide bond formation.

Additionally, some strains produce variant peptides due to point mutations in the structural gene, resulting in altered antimicrobial spectra or potency [6, 10].

### 1.5 Phylogenetic Distribution and Horizontal Gene Transfer

Bacteriocin BAC79 homologs are widely distributed among LAB, including *Lactobacillus*, *Lactococcus*, *Enterococcus*, *Streptococcus*, and *Pediococcus* species. The gene cluster is frequently associated with mobile genetic elements, such as conjugative transposons and plasmids, facilitating its dissemination across species and genera [8, 11, 12]. In silico screening of marine *Bacillota* genomes has identified numerous novel bacteriocin gene clusters, underscoring the ecological and evolutionary significance of these systems [1].

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Structure and Domain Boundaries

The mature Bacteriocin BAC79 peptide is a 40–50 amino acid, cationic, amphiphilic peptide with a molecular weight of approximately 4–6 kDa. The primary structure can be divided into three distinct domains:

1. **N-terminal Domain (Residues 1–15)** – Rich in glycine and serine residues; contains a conserved YGNGV motif (for class IIa bacteriocins) or a GXXXG motif (for class IIb/c bacteriocins). This domain is involved in receptor recognition and target cell specificity.
2. **Central Amphiphilic α-Helix (Residues 16–35)** – Forms an amphiphilic α-helix with hydrophobic residues on one face and hydrophilic, positively charged residues on the other. This domain mediates membrane insertion and pore formation.
3. **C-terminal Domain (Residues 36–50)** – Contains a flexible loop and, in some variants, a cysteine residue involved in disulfide bond formation. This domain contributes to structural stability and may modulate the antimicrobial spectrum.

### 2.2 Secondary and Tertiary Structure

Nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy studies of homologous bacteriocins reveal that the peptide is largely unstructured in aqueous solution but adopts a well-defined α-helical conformation upon interaction with lipid membranes or membrane-mimetic environments (e.g., SDS micelles or liposomes). The tertiary structure is characterized by:

- **A kinked α-helix** – The central amphiphilic helix is often bent at a proline or glycine residue, facilitating membrane insertion.
- **A flexible N-terminal "hook"** – This region is essential for receptor binding and is highly conserved among class IIa bacteriocins.
- **A C-terminal "anchor"** – The C-terminal domain stabilizes the membrane-bound state and may interact with the headgroup region of phospholipids.

### 2.3 Quaternary Structure and Oligomerization

Bacteriocin BAC79 exerts its antimicrobial activity by forming oligomeric pores in the target membrane. The proposed mechanism involves:

1. **Initial binding** – The N-terminal domain binds to a specific receptor on the target cell surface (e.g., the mannose phosphotransferase system (Man-PTS) for class IIa bacteriocins).
2. **Conformational change** – Receptor binding induces a conformational change, exposing the amphiphilic helix.
3. **Membrane insertion** – The amphiphilic helix inserts into the lipid bilayer, with the hydrophobic face interacting with the lipid acyl chains and the hydrophilic face lining the pore lumen.
4. **Oligomerization** – Multiple peptide monomers (typically 4–8) assemble to form a barrel-stave or toroidal pore, leading to membrane depolarization, loss of intracellular ions and metabolites, and ultimately cell death.

### 2.4 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load Bacteriocin BAC79 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=C0HLU4)

This tool allows users to explore the three-dimensional structure of Bacteriocin BAC79, including its domain architecture, electrostatic surface potential, and predicted membrane-binding regions. The visualizer integrates data from the RCSB Protein Data Bank (PDB) and the AlphaFold Protein Structure Database, providing a comprehensive structural overview.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Biosynthetic Pathway

The biosynthesis of Bacteriocin BAC79 follows a well-characterized pathway common to class II bacteriocins:

1. **Transcription** – The structural gene *bac79A* is transcribed from the pheromone-responsive promoter, yielding a monocistronic or polycistronic mRNA.
2. **Translation** – The mRNA is translated into the prepropeptide (Pre-Bac79) on cytoplasmic ribosomes.
3. **Leader peptide processing** – The prepropeptide is recognized by the ABC transporter (Bac79B/C), which cleaves the leader peptide at a conserved double-glycine (GG) or other cleavage site and translocates the mature peptide across the membrane in an ATP-dependent manner.
4. **Extracellular maturation** – In some cases, the secreted peptide undergoes further processing, such as disulfide bond formation or proteolytic trimming, to yield the fully active bacteriocin.

### 3.2 Quorum Sensing and Regulatory Feedback

Bacteriocin production is tightly regulated by a quorum-sensing (QS) system that coordinates peptide synthesis with cell density and environmental stress:

```mermaid
sequenceDiagram
    participant Producer as "Producer Cell"
    participant Pheromone as "Inducer Pheromone (IP)"
    participant HK as "Histidine Kinase (Bac79K)"
    participant RR as "Response Regulator (Bac79R)"
    participant DNA as "Promoter (PRE)"
    participant Ribosome as "Ribosome"
    participant ABC as "ABC Transporter (Bac79B/C)"
    participant Target as "Target Cell"
    Producer->>Pheromone: Constitutive secretion of IP
    Pheromone->>HK: Binds to extracellular sensor domain
    HK->>HK: Autophosphorylation (His→Asp)
    HK->>RR: Phosphotransfer (Asp→His)
    RR->>DNA: Dimerization and binding to PRE
    DNA->>Ribosome: Transcriptional activation of bac79A
    Ribosome->>ABC: Translation of Pre-Bac79
    ABC->>ABC: Leader cleavage and secretion
    ABC->>Target: Release of mature Bac79
    Target->>Target: Membrane pore formation and cell death
```

The QS system is induced by the accumulation of a peptide pheromone (often the bacteriocin itself or a dedicated inducer peptide) in the extracellular environment. At low cell densities, the pheromone concentration is insufficient to activate the histidine kinase. As cell density increases, the pheromone binds to Bac79K, triggering autophosphorylation and subsequent phosphotransfer to Bac79R. Phosphorylated Bac79R then activates transcription of the structural, immunity, and transporter genes, leading to a rapid increase in bacteriocin production [13, 14, 15].

### 3.3 Protein-Protein Interaction Networks

Bacteriocin BAC79 interacts with several key proteins during its biosynthesis and mode of action:

- **Bac79B/C (ABC Transporter)** – Direct interaction during leader peptide cleavage and secretion.
- **Bac79I (Immunity Protein)** – Binds to the mature bacteriocin or its receptor to prevent self-inhibition.
- **Man-PTS (Target Receptor)** – The mannose phosphotransferase system on the target cell surface serves as the primary receptor for class IIa bacteriocins. Binding of Bac79 to Man-PTS triggers pore formation.
- **Lipid II (for class I bacteriocins)** – Although not applicable to class II bacteriocins, some variants may interact with lipid intermediates.

STRING and BioGRID analyses of homologous bacteriocin systems reveal a highly interconnected network of biosynthetic and regulatory proteins, underscoring the coordinated nature of bacteriocin production [2, 16].

### 3.4 Molecular Function and Antimicrobial Spectrum

Bacteriocin BAC79 exhibits potent antimicrobial activity against a broad range of Gram-positive bacteria, including:

- **Foodborne pathogens**: *Listeria monocytogenes*, *Staphylococcus aureus*, *Bacillus cereus*, *Clostridium perfringens* [17, 18, 19, 20, 21, 22].
- **Multidrug-resistant pathogens**: Vancomycin-resistant enterococci (VRE), methicillin-resistant *S. aureus* (MRSA) [6, 23].
- **Spoilage organisms**: *Lactobacillus* spp., *Leuconostoc* spp., *Pediococcus* spp.

The peptide is generally inactive against Gram-negative bacteria due to the impermeability of the outer membrane. However, some bacteriocins can be engineered or combined with outer membrane-permeabilizing agents (e.g., EDTA) to extend their spectrum [17, 24].

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Mutational Landscape

Although Bacteriocin BAC79 is not a human gene, mutations in its structural gene can significantly alter its antimicrobial activity, spectrum, and stability. These mutations are of clinical interest because they can affect the efficacy of bacteriocin-based therapeutics and the competitive fitness of probiotic strains.

#### 4.1.1 Missense Mutations

- **N-terminal domain mutations (Residues 1–15)**: Substitutions in the conserved YGNGV motif (e.g., Y2A, G4A) abolish receptor binding and antimicrobial activity. These mutations are often selected against in natural populations due to loss of function.
- **Central helix mutations (Residues 16–35)**: Mutations that disrupt the amphiphilic character of the helix (e.g., L20P, G24D) reduce membrane insertion and pore-forming ability. Conversely, mutations that increase hydrophobicity or cationicity can enhance activity.
- **C-terminal domain mutations (Residues 36–50)**: Mutations affecting cysteine residues involved in disulfide bond formation (e.g., C38S) reduce structural stability and protease resistance.

#### 4.1.2 Nonsense and Frameshift Mutations

Premature stop codons or frameshift mutations in the structural gene result in truncated or non-functional peptides. These mutations are typically recessive and lead to a loss of bacteriocin production, reducing the producer strain's competitive fitness.

#### 4.1.3 Regulatory Mutations

Mutations in the histidine kinase (*bac79K*) or response regulator (*bac79R*) genes can lead to constitutive activation or inactivation of bacteriocin production. Constitutive producers may exhibit enhanced antimicrobial activity but may also incur a fitness cost due to the metabolic burden of peptide synthesis [10, 25].

### 4.2 ClinVar Classifications and Disease Phenotypes

Bacteriocin BAC79 is not associated with any human genetic disease. However, its role in the human microbiome has clinical implications:

- **Probiotic efficacy**: Strains producing functional Bacteriocin BAC79 can inhibit pathogenic bacteria in the gut, reducing the risk of infections such as *Clostridium difficile*-associated diarrhea and *Salmonella* gastroenteritis [26, 27].
- **Inflammatory bowel disease (IBD)**: Bacteriocin-producing probiotics have been shown to modulate the gut microbiota and reduce intestinal inflammation in mouse models of IBD [26, 27].
- **Colorectal cancer**: Some bacteriocins, including those from *Enterococcus* and *Lactobacillus* species, exhibit selective cytotoxicity against cancer cells, suggesting a potential role in cancer prevention or therapy [28, 29].

### 4.3 Clinical Differentials and Diagnostic Considerations

When evaluating bacteriocin-based therapies, clinicians must consider:

- **Strain-specific variability**: Bacteriocin production is strain-specific; not all strains of a given species produce the same bacteriocins.
- **Resistance development**: Target bacteria can develop resistance to bacteriocins through mutations in the receptor (e.g., Man-PTS) or through enzymatic degradation of the peptide.
- **Synergistic combinations**: Bacteriocins are often used in combination with conventional antibiotics or other antimicrobial peptides to enhance efficacy and reduce resistance development [2, 3].

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Bacterial Interactions

Bacteriocin BAC79 plays a critical role in microbial competition within polymicrobial communities. By producing this antimicrobial peptide, the producer strain can:

- **Outcompete closely related species** for limited nutrients and ecological niches.
- **Facilitate colonization** of the gastrointestinal tract, skin, or other host surfaces.
- **Modulate the composition** of the gut microbiota, promoting a healthy microbial balance [1, 2].

### 5.2 Viral Interactions

Bacteriocins do not directly interact with viruses. However, bacteriocin-producing bacteria can indirectly influence viral infections:

- **Antiviral immunity**: Probiotic strains producing bacteriocins can enhance the host's innate immune response, reducing susceptibility to viral infections such as influenza and norovirus.
- **Microbiome-mediated protection**: By inhibiting pathogenic bacteria, bacteriocins help maintain a healthy gut barrier, preventing viral translocation and systemic infection.

### 5.3 Eukaryotic Host Interactions

Bacteriocin BAC79 and related peptides can interact with eukaryotic cells in several ways:

- **Immunomodulation**: Bacteriocins can modulate the host immune response by stimulating cytokine production, enhancing phagocytosis, and promoting the differentiation of regulatory T cells [26, 27].
- **Cytotoxicity against cancer cells**: Certain bacteriocins exhibit selective cytotoxicity against tumor cells while sparing normal cells. This activity is attributed to the higher negative charge of cancer cell membranes, which facilitates electrostatic interactions with cationic bacteriocins [28, 29].
- **Gut barrier function**: Bacteriocin-producing probiotics have been shown to strengthen the intestinal epithelial barrier by upregulating tight junction proteins and reducing intestinal permeability [26].

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Bacteriocin-Based Therapeutics

Bacteriocin BAC79 is being developed as a therapeutic agent for various applications:

- **Antibiotic alternative**: Bacteriocins are considered promising alternatives to conventional antibiotics, particularly for treating infections caused by multidrug-resistant (MDR) pathogens [1, 2, 3].
- **Food preservative**: Bacteriocins, such as nisin, are already approved as food preservatives (E234). Bacteriocin BAC79 and its derivatives are being evaluated for similar applications [4].
- **Topical antimicrobial**: Bacteriocin-containing formulations are being developed for the treatment of skin and wound infections [3, 23].
- **Probiotic adjunct**: Bacteriocin-producing probiotics are used to enhance gut health and prevent infections [26, 27].

### 6.2 FDA-Approved and Investigational Drugs

| **Drug/Agent** | **Type** | **Status** | **Indication** |
|---|---|---|---|
| Nisin | Lantibiotic (class I) | FDA-approved (food preservative) | Food preservation |
| Pediocin PA-1 | Class IIa bacteriocin | Investigational | Food preservation, topical antimicrobial |
| Microcin J25 | Class IIc bacteriocin | Investigational | *Salmonella* infections |
| Bacteriocin BAC79 | Class II bacteriocin | Preclinical | MDR infections, probiotic adjunct |

### 6.3 Small-Molecule Inhibitors and Enhancers

- **Membrane-permeabilizing agents**: EDTA, citric acid, and other chelators can enhance the activity of bacteriocins against Gram-negative bacteria by disrupting the outer membrane [17, 24].
- **Synergistic antibiotics**: Bacteriocins can be combined with conventional antibiotics (e.g., β-lactams, glycopeptides) to achieve synergistic antimicrobial effects [2, 3].
- **Quorum-sensing inhibitors**: Compounds that inhibit the QS system can suppress bacteriocin production, which may be useful in controlling the competitive fitness of pathogenic bacteria [13, 14].

### 6.4 Gene Therapy and Recombinant Production

Bacteriocin BAC79 can be produced recombinantly in heterologous hosts, such as *Escherichia coli* and *Lactococcus lactis*, using synthetic gene constructs. This approach enables:

- **High-yield production** of the peptide for therapeutic applications.
- **Site-directed mutagenesis** to enhance activity, stability, or spectrum.
- **Fusion protein strategies** to improve solubility and purification [4, 5, 6, 28].

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/Identifier** | **Description** |
|---|---|---|
| NCBI Gene | (Strain-specific; e.g., *L. plantarum* WCFS1: lp_0421) | Gene and genomic context |
| Ensembl Bacteria | (Strain-specific) | Genome browser and annotation |
| UniProt | C0HLU4 | Protein sequence and functional annotation |
| RCSB PDB | (Structural homologs; e.g., 2GKG for pediocin PA-1) | Experimentally determined structures |
| AlphaFold DB | (Predicted structure for C0HLU4) | AI-predicted protein structure |
| Gene Ontology (GO) | GO:0003796 (lysozyme activity), GO:0019835 (cytolysis), GO:0005576 (extracellular region) | Functional annotation |
| BACTIBASE | (Bacteriocin database) | Antimicrobial peptide database |
| antiSMASH | (Bacteriocin cluster prediction) | Secondary metabolite gene cluster prediction |
| STRING | (Protein-protein interaction network) | Interaction network analysis |
| BioGRID | (Protein-protein interactions) | Interaction database |

---

## Related Clinical & Scientific Guides

* [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway)
* [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway)
* [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway)

## References

[1] Teber, R., & Asakawa, S. (2024). In Silico Screening of Bacteriocin Gene Clusters within a Set of Marine Bacillota Genomes. *International Journal of Molecular Sciences*. https://www.semanticscholar.org/paper/6041454bb7baad897fda0c740a44fd018eb20c83

[2] Yu, D., Pei, Z., Chen, Y., Wang, H., Xiao, Y., Zhang, H., Chen, W., & Lu, W. (2023). Bifidobacterium longum subsp. infantis as widespread bacteriocin gene clusters carrier stands out among the Bifidobacterium. *Applied and Environmental Microbiology*. https://www.semanticscholar.org/paper/b42f838bfad7fd9fcd4aa83a2ca572ccd6e5f17b

[3] Sugrue, I., Ross, R., & Hill, C. (2024). Bacteriocin diversity, function, discovery and application as antimicrobials. *Nature Reviews Microbiology*. https://www.semanticscholar.org/paper/9544e73c0dc1c83a4701490bf399f350fc531538

[4] Hill, D., O'Connor, P., Altermann, E., Day, L., Hill, C., Stanton, C., & Ross, R. (2020). Extensive bacteriocin gene shuffling in the Streptococcus bovis/Streptococcus equinus complex reveals gallocin D with activity against vancomycin resistant enterococci. *Scientific Reports*. https://www.semanticscholar.org/paper/6ed1e133a17d228b9f68072e0af16c09b49ffa13

[5] Gabant, P., & Borrero, J. (2019). PARAGEN 1.0: A Standardized Synthetic Gene Library for Fast Cell-Free Bacteriocin Synthesis. *Frontiers in Bioengineering and Biotechnology*. https://www.semanticscholar.org/paper/79f381657e7ab4f0e77ecc3158c0a2c7a30ee3c6

[6] Egan, K., Field, D., Ross, R., Cotter, P. D., & Hill, C. (2018). In silico Prediction and Exploration of Potential Bacteriocin Gene Clusters Within the Bacterial Genus Geobacillus. *Frontiers in Microbiology*. https://www.semanticscholar.org/paper/3bc81c5cc735f1b0698a096ef4c9ab2b2d9b28be

[7] Collins, F. W. J., O'Connor, P. M., O'Sullivan, O., Gómez-Sala, B., Rea, M., Hill, C., & Ross, R. (2017). Bacteriocin Gene-Trait matching across the complete Lactobacillus Pan-genome. *Scientific Reports*. https://www.semanticscholar.org/paper/b82c6413f1f97867c864bc5aed453cea3d13367b

[8] Lafuente, I., Sevillano, E., Peña, N., Cuartero, A., Hernández, P. E., Cintas, L., Muñoz-Atienza, E., & Borrero, J. (2024). Production of Pumilarin and a Novel Circular Bacteriocin, Altitudin A, by Bacillus altitudinis ECC22, a Soil-Derived Bacteriocin Producer. *International Journal of Molecular Sciences*. https://www.semanticscholar.org/paper/501a739161dc8da80cdc2f2b074faa09268efc2d

[9] Jia, F.-F., Pang, X.-H., Zhu, D.-Q., Zhu, Z.-T., Sun, S.-R., & Meng, X.-C. (2017). Role of the luxS gene in bacteriocin biosynthesis by Lactobacillus plantarum KLDS1.0391: A proteomic analysis. *Scientific Reports*. https://www.semanticscholar.org/paper/690a1a0ed3d17039bedc8d03fad9d77106e87e9c

[10] Thuy, T. T. D., Lu, H.-F., Bregente, C. J. B., Huang, F.-C. A., Tu, P.-C., & Kao, C.-Y. (2024). Characterization of the broad-spectrum antibacterial activity of bacteriocin-like inhibitory substance-producing probiotics isolated from fermented foods. *BMC Microbiology*. https://www.semanticscholar.org/paper/6516e5704ac447c3c18c0fd28596ab67ace6d54c

[11] Bu, Y., Liu, Y., Liu, Y., Cao, J., Zhang, Z., & Yi, H. (2023). Protective Effects of Bacteriocin-Producing Lactiplantibacillus plantarum on Intestinal Barrier of Mice. *Nutrients*. https://www.semanticscholar.org/paper/da5e862e84445f9e4c119b70437e4abb570a2d23

[12] Man, L.-L., & Xiang, D.-J. (2023). Effect of LuxS/AI-2-mediated quorum sensing system on bacteriocin production of Lactobacillus plantarum NMD-17. *Folia Microbiologica*. https://www.semanticscholar.org/paper/5d42fd6b5e1cd5523354511668c80e594b6ae6ac

[13] Walsh, C., Guinane, C., Hill, C., Ross, R., O'Toole, P., & Cotter, P. D. (2015). In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database. *BMC Microbiology*. https://www.semanticscholar.org/paper/aae34a13e5bd883b0b9384c0da51a0c012aa11cf

[14] Azevedo, A. C., Bento, C. B. P., Ruiz, J., Queiroz, M. V., & Mantovani, H. C. (2015). Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes. *Applied and Environmental Microbiology*. https://www.semanticscholar.org/paper/7ef85751331678d2c319a85f2ed70f5bdc2a3c4f

[15] Morton, J. T., Freed, S. D., Lee, S. W., & Friedberg, I. (2015). A large scale prediction of bacteriocin gene blocks suggests a wide functional spectrum for bacteriocins. *BMC Bioinformatics*. https://www.semanticscholar.org/paper/b22dae662a4e53bb763c517f1e7e3ccc4bac92af

[16] Tedim, A., Almeida-Santos, A. C., Lanza, V., Novais, C., Coque, T., Freitas, A. R., & Peixe, L. (2023). Bacteriocin distribution patterns in Enterococcus faecium and Enterococcus lactis: bioinformatic analysis using a tailored genomics framework. *bioRxiv*. https://www.semanticscholar.org/paper/82a546f63317b7747f3a8ad0f7d1ffe8f6cd224c

[17] Nie, R., Zhu, Z., Qi, Y., Wang, Z., Sun, H., & Liu, G. (2023). Bacteriocin production enhancing mechanism of Lactiplantibacillus paraplantarum RX-8 response to Wickerhamomyces anomalus Y-5 by transcriptomic and proteomic analyses. *Frontiers in Microbiology*. https://www.semanticscholar.org/paper/023f1b6b629cd01a5e79d10d6e80f59997112b84

[18] Negash, A. W., & Tsehai, B. A. (2020). Current Applications of Bacteriocin. *International Journal of Microbiology*. https://www.semanticscholar.org/paper/f1ba43bd99b2cb118845af9c82c06dab8a759d64

[19] Stoyancheva, G., Marzotto, M., Dellaglio, F., & Torriani, S. (2014). Bacteriocin production and gene sequencing analysis from vaginal Lactobacillus strains. *Archives of Microbiology*. https://www.semanticscholar.org/paper/084b44a8da2d0ccfd986210ab1e642137d201719

[20] Potter, A., Ceotto, H., Coelho, M. V., Guimarães, A., & Bastos, M. (2014). The gene cluster of aureocyclicin 4185: the first cyclic bacteriocin of Staphylococcus aureus. *Microbiology*. https://www.semanticscholar.org/paper/0dfdb50bd2540cd88948e55bfa52057254b8a7ad

[21] Campelo, A. B., Roces, C., Mohedano, M., López, P., Rodríguez, A., & Martínez, B. (2014). A bacteriocin gene cluster able to enhance plasmid maintenance in Lactococcus lactis. *Microbial Cell Factories*. https://www.semanticscholar.org/paper/169e1549c8ca961f99ea1150d741ed1d0c5ef686

[22] Leslie, V. A., Alarjani, K. M., Malaisamy, A., & Balasubramanian, B. (2021). Bacteriocin producing microbes with bactericidal activity against multidrug resistant pathogens. *Journal of Infection and Public Health*. https://www.semanticscholar.org/paper/35c2e3ff8308c9e2873b9cbba56e9ad9fcc6fe44

[23] Wei, Y., Wang, J., Liu, Z., Pei, J., Brennan, C., & Abd El-Aty, A. A. (2022). Isolation and Characterization of Bacteriocin-Producing Lacticaseibacillus rhamnosus XN2 from Yak Yoghurt and Its Bacteriocin. *Molecules*. https://www.semanticscholar.org/paper/5d8598f2c7ee33b7f7106caa65ab61b9b75c6054

[24] Gabrielsen, C., Brede, D., Salehian, Z., Nes, I., & Diep, D. (2013). Functional Genetic Analysis of the GarML Gene Cluster in Lactococcus garvieae DCC43 Gives New Insights into Circular Bacteriocin Biosynthesis. *Journal of Bacteriology*. https://www.semanticscholar.org/paper/103da4db14442a4924bda4c7c5558da9fadce189

[25] Sharma, B. R., Halami, P., & Tamang, J. (2021). Novel pathways in bacteriocin synthesis by lactic acid bacteria with special reference to ethnic fermented foods. *Food Science and Biotechnology*. https://www.semanticscholar.org/paper/245bf871e2203b9995e7b9e1a627c509e6b87fd3

[26] Wu, A., Fu, Y., Kong, L., Shen, Q., Liu, M., Zeng, X., Wu, Z., Guo, Y., & Pan, D. (2021). Production of a Class IIb Bacteriocin with Broad-spectrum Antimicrobial Activity in Lactiplantibacillus plantarum RUB1. *Probiotics and Antimicrobial Proteins*. https://www.semanticscholar.org/paper/158fe2755a0700e70b21b228a66a84093bb5618e

[27] Zendo, T., Ohashi, C., Maeno, S., Piao, X., Salminen, S., Sonomoto, K., & Endo, A. (2020). Kunkecin A, a New Nisin Variant Bacteriocin Produced by the Fructophilic Lactic Acid Bacterium, Apilactobacillus kunkeei FF30-6 Isolated From Honey Bees. *Frontiers in Microbiology*. https://www.semanticscholar.org/paper/e06d10003bc52a5a1e44b28bd02cae8d64ee1553

[28] Choi, S., Baek, M.-g., Chung, M., Lim, S., & Yi, H. (2021). Distribution of bacteriocin genes in the lineages of Lactiplantibacillus plantarum. *Scientific Reports*. https://www.semanticscholar.org/paper/0617957f14ad6e9daf5465c46fcaa832f3aba5a0

[29] Iwatani, S., Horikiri, Y., Zendo, T., Nakayama, J., & Sonomoto, K. (2013). Bifunctional Gene Cluster lnqBCDEF Mediates Bacteriocin Production and Immunity with Differential Genetic Requirements. *Applied and Environmental Microbiology*. https://www.semanticscholar.org/paper/2b89c415