Dual Nature of Bacteriophages: Friends or Foes in Minimally Processed Food Products—A Comprehensive Review
Abstract
1. Introduction
2. Minimally Processed Food
2.1. Microbiological Hazards in Minimally Processed Food Products
2.2. Methods of Preserving Minimally Processed Foods
3. Food as a Carrier of Antibiotic-Resistant Bacteria
3.1. Antibiotics and Mechanisms of Their Action
3.2. Antibiotic Resistance and Mechanisms of Bacterial Resistance
- i.
- MDR (multidrug resistance): the strain shows resistance to at least one antibiotic from three or more different classes of antibacterial drugs;
- ii.
- XDR (extensively drug resistance): the strain is resistant to at least one antibiotic from all but a maximum of two classes of antibiotics used to treat infections caused by the microorganism;
- iii.
3.3. Natural Resistance of Bacteria to Antibiotics
4. Bacteriophages as a Natural Method of Biocontrol of Bacterial Microbiota in Food
4.1. Phage Particle Structure
4.2. Bacteriophage Replication Cycles
4.3. Benefits and Risks of Using Bacteriophages
4.4. Invisible Guardians: The Role of Bacteriophages in Food Safety
4.4.1. Primary Production
4.4.2. Bio-Sanitization
4.4.3. Biopreservation
4.5. The Dark Side of Phages: Challenges in Food Production and Fermentation
4.6. Risks and Implications of Contaminants in Phage-Based Preparations
4.7. Legal Aspects Related to the Use of Bacteriophages in the Agri-Food Industry
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Abi | abortive infection system |
ACE | accessory cholera enterotoxin |
AIDS | acquired immunodeficiency syndrome |
AMR | antimicrobial resistance |
AMS | antibiotic stewardship |
ARG | antibiotic resistance gene |
BREX | bacteriophage exclusion |
BVS | Bacterial Viruses Subcommittee |
cAMP | cyclic adenosine monophosphate |
Cas | CRISPR-associated genes |
CDC | Centers for Disease Control and Prevention |
CFU | colony-forming unit |
CIP | clean-in-place |
CRISPR | clustered, regularly interspaced short palindromic repeats |
CT | cholera toxin |
DHF | dihydrofolate |
DISARM | defense island system associated with restriction modification |
dsDNA | double-stranded deoxyribonucleic acid |
dsRNA | double-stranded ribonucleic acid |
ECDC | European Centre for Disease Prevention and Control |
EFSA | European Food Safety Authority |
EHEC | enterohemorrhagic Escherichia coli |
EMA | European Medicines Agency |
EU | European Union |
FAO | Food and Agriculture Organization |
FDA | Food and Drug Administration |
FEEDAP | Panel on Additives and Products or Substances used in Animal Feed |
GEI | genome island |
GRAS | generally recognized as safe |
HGT | horizontal gene transfer |
HHP | high hydrostatic pressure |
HIIET PAS | Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences |
HMC | glucosylated hydroxymethylcytosine |
ICTV | International Committee on Taxonomy of Viruses |
LAB | lactic acid bacteria |
LPS | lipopolysaccharide |
MDR | multidrug-resistant, multidrug resistance |
MPF | minimally processed food |
MRSA | methicillin-resistant Staphylococcus aureus |
PABA | p–aminobenzoic acid |
PAHO | Pan American Health Organization |
PAI | pathogenicity island |
PAM | protospacer-adjacent motif |
PDR | pandrug resistance |
PFU | plaque-forming unit |
PIP | phage infection protein |
qPCR | quantitative polymerase chain reaction |
R-M | restriction–modification |
ROS | reactive oxygen species |
SCFA | short-chain fatty acid |
Sie | superinfection exclusion mechanism |
TA | toxin-antitoxin |
TEM | transmission electron microscopy |
THF | tetrahydrofolate |
TNB | total number of bacteria |
USDA | United States Department of Agriculture |
WHO | World Health Organization |
XDR | extensively drug resistance |
ZOT | zonula occludens toxin |
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Saprophytic Bacteria | ||||
---|---|---|---|---|
Food Matrices (Storage Conditions) | Bacteria | Phage/Phage Cocktail (Application Method) | Main Results | Reference |
alfalfa sprouts kale sprouts lentil sprouts sunflower sprouts radish sprouts (20 °C/350 mbar) | natural bacterial microbiota of the product | cocktail of 18 phages (spraying and an absorption pad) | The spraying method was significantly more effective, achieving a maximum reduction of 1.5 log CFU g−1 after 48 h, while phage-soaked pads reduced bacterial counts by only 0.27–0.79 log CFU g−1. | [77] |
rucola (20 °C/protective atmosphere) | natural bacterial microbiota of the product | cocktail of 43 phages (spraying, and an absorption pad) | The spray and absorbent pad applications reduced TNB* growth similarly after 6 h. During storage, control samples saw a 3-log increase, while the phage cocktail applications reduced TNB by 99% (2-log reduction). | [242] |
mixed-leaf salad with carrot (20 °C/protective atmosphere) | Spray and absorbent pad applications showed no significant bacterial reduction at 6 h but significantly reduced TNB at 48 h. The absorbent pad was more effective on the food product. During storage, microbial counts in phage spray tests increased by 1 log, while both methods reduced TNB by 99.9% compared to controls. | |||
mixed-leaf salad with beetroot (20 °C/protective atmosphere) | The spray and absorbent pad had little effect on TNB at 6 h but significantly reduced growth at 48 h. Spraying was more effective on the product. Both methods reduced TNB by 99% (2-log reduction) compared to controls. | |||
washed spinach (20 °C/protective atmosphere) | The spray and absorbent pad significantly reduced bacterial growth at 6 h, but no inhibitory effect was observed at 24 h and 48 h. | |||
unwashed spinach (20 °C/protective atmosphere) | Applying the spray and absorbent pad to unwashed spinach significantly reduced TNB growth at 6 h and 24 h, but not at 48 h. | |||
broccoli sprouts (20 °C/protective atmosphere) | natural bacterial microbiota of the product | cocktail of 29 phages (spraying and an absorption pad) | The application of the spray and absorbent pad notably inhibited microbial growth in the product environment after 24 h. During storage, TNB in the control sample increased by less than half a logarithmic unit, whereas in the phage-treated samples, it decreased by a comparable amount. | [243] |
spinach leaves (20 °C/protective atmosphere) | Both spraying and absorbent pad application effectively suppressed microbial growth in the product environment within 6 h compared to the control. The application of the phage cocktail on spinach leaves led to a reduction in TNB by half to nearly one log unit, depending on the method used. | |||
freshly squeezed carrot–celery juice (20 °C/protective atmosphere) | cocktail of 29 phages (phage suspension (5% of the volume of juice)) | Throughout the 48 h storage period, TNB in the control sample remained largely unchanged. However, applying the phage suspension to the juice significantly reduced TNB within 6 h. During storage, TNB in the product treated with the phage mixture continued to decline steadily. | ||
fresh-cut mixed vegetables (iceberg lettuce, carrot, and purple cabbage) (20 °C/nitrogen gas) | E. coli strain K12 | cocktail of coliphages (Escherichia phage SUT_E420, Escherichia phage SUT_E520, Escherichia phage SUT_E1520, and Escherichia phage SUT_E1620) (phage suspension) | When the coliphage cocktail was applied, no E. coli were detected in treated samples on day 0, showing a reduction of approximately 3.8 log CFU mL−1. However, E. coli levels gradually increased to 0.9–1.4 log CFU mL−1. Despite this, bacterial counts in treated samples remained significantly lower than in untreated samples throughout the experiment, with a 2.4 log CFU mL−1 reduction still observed by the end of day 3. | [244] |
lettuce leaves (Lactuca sativa var iceberg) (no data) | Enterobacter kobei strain AG07E | bacteriophage FENT2 (single-phage treatment by immersion) | Immersing lettuce leaves in the phage suspension effectively reduced the presence of the E. kobei strain AG07E on their surface, resulting in a significant reduction of 1 ± 0.06 log. | [245] |
Bacterial Pathogens | ||||
Food Matrices (Storage Conditions) | Bacteria | Phage/Phage Cocktail (Application Method) | Main Results | Reference |
radish sprouts (20 °C/normal atmosphere) | S. Virchow strain KKP 997 | cocktail of four salmophages (KKP 3265, KKP 3266, KKP 3267, and KKP 3332) (spraying, and an absorption pad) | In all cases, the absorbent pad more effectively inhibited Salmonella growth in the food matrix, reducing it by up to 2 log units, compared to the spray method. | [246] |
S. Itami strain KKP 1001 | ||||
S. Enteritidis strain KKP 3078 | ||||
S. Typhimurium strain KKP 3079 | ||||
HHP-preserved carrot–mango–apple juice(4 °C) | S. enterica subsp. enterica serovar 6,8:l,-:1,7 strain KKP 1762 | single or phage cocktail: Salmonella phage KKP 3822, Salmonella phage KKP 3829, Salmonella phage KKP 3830, and Salmonella phage KKP 3831 (phage suspension) | Applying either individual phages or a phage cocktail to juice significantly reduced Salmonella growth, except when Salmonella phage KKP 3830 was added to juice infected with S. enterica strain KKP 1762, where no significant reduction occurred. Pathogen growth was most effectively restricted by the phage targeting the specific bacterial strain. The phage cocktail reduced the growth of both bacterial pathogen strains by approximately one log unit (90%) by the end of refrigerated storage, compared to untreated control samples. | [247] |
S. Typhimurium strain KKP 3080 | ||||
raw carrot–apple juice (4 °C or 20 °C) | S. enterica subsp. enterica serovar 6,8:l,-:1,7 strain KKP 1762 | phage cocktail: Salmonella phage KKP 3822, Salmonella phage KKP 3829, Salmonella phage KKP 3830, and Salmonella phage KKP 3831 (phage suspension) | Addition of a phage cocktail to juice infected with S. enterica strain KKP 1762 and storage at 4 °C for 24 h significantly reduced the pathogen level. For S. Typhimurium strain KKP 3080, a significant reduction was observed after 48 h. At 20 °C, control samples showed a one-fold increase in Salmonella counts after 24 h, while phage-treated samples showed a significant reduction. After two days at 20 °C or seven days at 4 °C, no Salmonella were detected in either control or phage-treated samples (strong pH changes during storage). | |
S. Typhimurium strain KKP 3080 | ||||
alfalfa sprout seeds (22 °C/in the dark) | S. Enteritidis strain S5-483, S. Newport strain S5-639, S. Muenchen strain S5-504, and S. Typhimurium strain S5-5336 | phage cocktail (SE14, SE20, SF6) (single-phage treatment or repeated-phage treatment via washing) | The results indicate that S. Enteritidis was the most susceptible to both bacteriophage cocktails, showing a reduction of approximately 2.5 log CFU mL−1 on day 0 with cocktails SE14, SF5, and SF6. While S. enterica populations across all strains continued to grow despite daily bacteriophage applications, their growth rate was significantly lower compared to a single bacteriophage application. The extent of reduction varied depending on the S. enterica strain, but the findings suggest that repeated-phage treatment during sprout germination are more effective at reducing S. enterica populations than single-phage application. | [248] |
phage cocktail (SE14, SF5, SF6) (single-phage treatment or repeated-phage treatment via washing) | ||||
green juice (4 °C and 25 °C) | Shiga toxin-producing E. coli O157:H7 (STEC) strain ATCC 43895 | bacteriophage vB_ESM-pEJ01 (phage suspension) | The phage’s effectiveness was evaluated by measuring viable host cell counts and Shiga toxin genes (stx1, stx2) abundance. After 24 h at 4 °C, phage treatment reduced host cells by 1.5 log CFU mL−1. At 25 °C, a 2.7 log CFU mL−1 reduction occurred after 12 h, but bacterial regrowth was observed at 24 h, suggesting better efficacy at 4 °C. Phage-treated samples also showed a significant decrease in stx gene abundance at 4 °C after 24 h and at 25 °C after 12 h. | [249] |
Romaine lettuce (10 °C) | E. coli O157 (STEC) | single coliphages (VE04, VE05, and VE07) | All tested phages successfully inhibited E. coli O157 on Romaine lettuce. After three days of storage at 10 °C, the log reduction compared to control groups ranged from 2.6 log CFU cm−2 to approximately 6 log CFU cm−2. | [250] |
celery (4 °C) | L. monocytogenes | cocktail of three lytic phages: LMPC01, LMPC02, and LMPC03 (spraying) | During 7 days of refrigerated storage, the phage cocktail with MOI = 10 reduced L. monocytogenes by 2.2 log CFU g−1. | [251] |
enoki mushroom (4 °C) | During 7 days of refrigerated storage, the phage cocktail with MOI = 10 reduced L. monocytogenes by 1.8 log CFU g−1. | |||
baby spinach (8 °C, 12 °C, and 25 °C) | L. monocytogenes strain 3053 | phage vB_LmoH_P61 (spraying) | After 6 days of storage at 8, 12, and 25 °C, the concentration of L. monocytogenes decreased by 1.93, 2.06, and 3.3 log CFU g−1, respectively. | [252] |
orange juice (4 °C) | L. monocytogenes strain LM008 | phage vB-LmoM-SH3-3 (phage suspension) | Phage treatment resulted in an approximately 3.9-log decrease in L. monocytogenes. | [253] |
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Wójcicki, M.; Sokołowska, B.; Górski, A.; Jończyk-Matysiak, E. Dual Nature of Bacteriophages: Friends or Foes in Minimally Processed Food Products—A Comprehensive Review. Viruses 2025, 17, 778. https://doi.org/10.3390/v17060778
Wójcicki M, Sokołowska B, Górski A, Jończyk-Matysiak E. Dual Nature of Bacteriophages: Friends or Foes in Minimally Processed Food Products—A Comprehensive Review. Viruses. 2025; 17(6):778. https://doi.org/10.3390/v17060778
Chicago/Turabian StyleWójcicki, Michał, Barbara Sokołowska, Andrzej Górski, and Ewa Jończyk-Matysiak. 2025. "Dual Nature of Bacteriophages: Friends or Foes in Minimally Processed Food Products—A Comprehensive Review" Viruses 17, no. 6: 778. https://doi.org/10.3390/v17060778
APA StyleWójcicki, M., Sokołowska, B., Górski, A., & Jończyk-Matysiak, E. (2025). Dual Nature of Bacteriophages: Friends or Foes in Minimally Processed Food Products—A Comprehensive Review. Viruses, 17(6), 778. https://doi.org/10.3390/v17060778