Phage Interactions Research Articles

Identification of amino acid residue in the Cronobacter sakazakii LamB responsible for the receptor compatibility of polyvalent coliphage CSP1.

Polyvalent phages have the advantage of a broader host range, overcoming the limitation of the narrow host range of phages. However, the limited molecular biological understanding on the host bacteria-polyvalent phage interaction hinders its effective application. Here, we revealed that the ability of the polyvalent phage CSP1 to infect Cronobacter sakazakii ATCC 29544 is disturbed by a single proline residue in the LamB protein and that lipopolysaccharide is used as an auxiliary receptor for CSP1 to support the adsorption and the subsequent infection of C. sakazakii. These results can contribute to a better understanding of the interaction between polyvalent phages and host bacteria for efficient phage application.

Phage against the Machine: The SIE-ence of Superinfection Exclusion.

Prophages can alter their bacterial hosts to prevent other phages from infecting the same cell, a mechanism known as superinfection exclusion (SIE). Such alterations are facilitated by phage interactions with critical bacterial components involved in motility, adhesion, biofilm production, conjugation, antimicrobial resistance, and immune evasion. Therefore, the impact of SIE extends beyond the immediate defense against superinfection, influencing the overall fitness and virulence of the bacteria. Evaluating the interactions between phages and their bacterial targets is critical for leading phage therapy candidates like Pseudomonas aeruginosa, a Gram-negative bacterium responsible for persistent and antibiotic-resistant opportunistic infections. However, comprehensive literature on the mechanisms underlying SIE remains scarce. Here, we provide a compilation of well-characterized and potential mechanisms employed by Pseudomonas phages to establish SIE. We hypothesize that the fitness costs imposed by SIE affect bacterial virulence, highlighting the potential role of this mechanism in the management of bacterial infections.

Genomic reconstruction of unclassified microorganisms: Analysis of CRISPR arrays and genes involved in defense mechanisms

The constant battle between bacteria and viruses has led to the development of sophisticated antiviral defense strategies by bacteria to defend themselves against phages. This study analyzed a marshland metagenome to identify and characterize bacterial antiviral defense systems and phage interactions. We assembled 210 metagenome-assembled genomes (MAGs) from environmental DNA extracted from Pallikaranai marshland soil and 37 unclassified MAGs were filtered. MIMAG standards were followed, 2 high-quality and 15 medium-quality unclassified MAGs were picked. MINCED was used to identify 137 CRISPR arrays in the quality MAGs, and ViroBLAST was used to identify the phages that interact with the bacteria. About 242 spacer sequences were extracted from the CRISPR arrays, of which 54 had significant matches in the ViroBLAST database. 7 unverified bacteriophage species were also detected in the MAGs. The viral group of Caudoviricetes phage elements were identified as a frequent genome terminal repeat. The PADLOC identified 11 genes involved as a defense system in the MAGs. The PD-T4-6 defense system was found to be prevalent in 15 different unclassified MAGs. This study presents valuable insights intothe adaptations of unclassified bacteria to bacteriophages, as well as the genes used by these bacteria as a defense mechanism.

Acinetobacter baumannii satellite phage Aci01-2-Phanie depends on a helper myophage for its multiplication.

We report the discovery of a satellite-helper phage system with a novel type of dependence on a tail donor. The Acinetobacter baumannii satellite podovirus Aci01-2-Phanie (short name Phanie) uses a phage phi29-like DNA replication and packaging mode. Its linear 11,885 bp dsDNA genome bears 171 bp inverted terminal repeats (ITR). Phanie is related to phage DU-PP-III from Pectobacterium and to members of the Astrithrvirus from Salmonella enterica. Together, they form a new clade of phages with 27% to 30% identity over the whole genome. Detailed 3D protein structure prediction and mass spectrometry analyses demonstrate that Phanie encodes its capsid structural genes and genes necessary to form a short tail. However, our study reveals that Phanie virions are non-infectious unless they associate with the contractile tail of an unrelated phage, Aci01-1, to produce chimeric myoviruses. Following the coinfection of Phanie with myovirus Aci01-1, hybrid viral particles composed of Phanie capsids and Aci01-1 contractile tails are assembled together with Phanie and Aci01-1 particles.IMPORTANCEThere are few reported cases of satellite-helper phage interactions but many more may be yet undiscovered. Here we describe a new mode of satellite phage dependence on a helper phage. Phanie, like phage phi29, replicates its linear dsDNA by a protein primed-mechanism and protects it inside podovirus-like particles. However, these particles are defective, requiring the acquisition of the tail from a myovirus helper for production of infectious virions. The formation of chimeras between a phi29-like podovirus and a helper contractile tail reveals an unexpected association between very different bacterial viruses.

Editorial: Bacteriophage and host interactions

Editorial: Bacteriophage and host interactions

Amino-functionalized graphene oxide affects bacteria–phage interactions in aquatic environments

The widespread use of graphene family nanomaterials (GFNs) in mass production has resulted in their release into the atmosphere, soil and water environment through various processes. Among these, the water environment is particularly affected by GFN pollution. Our previous study has demonstrated the impact of graphene oxide (GO) on bacteria–phage interactions in natural systems. However, the effects of amino-functionalized GO with a positive charge on bacteria–phage interactions in aquatic environments remain unclear. In the present study, we found that amino-functionalized graphene oxide (AGO) (0.05 mg/mL) inhibited the growth of Pseudomonas aeruginosa Y12. Furthermore, treating P. aeruginosa Y12 and phage with AGO (0.05 mg/mL) led to a reduced ratio of phage to bacteria, indicating that AGO can inhibit phage infection of bacteria. Additionally, the acidic environment exacerbated this effect by promoting electrostatic adsorption between the positively charged AGO and the negatively charged phage. Finally, a field water body intervention experiment showed that the richness and diversity of bacterial communities in six water samples changed due to AGO exposure, as revealed by Illumina analysis based on the bacterial 16S rRNA gene. These findings offer valuable insights into the environmental impacts of GFNs.

In vitro investigation into the dynamics between Acinetobacter baumannii, bacteriophage, and mammalian bronchial epithelial cells

Antibiotic resistance is escalating due to the rapid emergence of multidrug-resistant bacteria and the stagnation in new antibiotic development. Bacteriophage, a natural enemy of bacteria, has re-emerged as a promising alternative in the post-antibiotic era. However, none of the recently completed randomized, placebo-controlled, and double-blinded clinical trials on phage therapy could confirm its efficacy. One of the major impediments is the lack of understanding of the phage, bacteria, and host body interactions. Our work investigates the dynamics between Acinetobacter baumannii, bacteriophage, and a mammalian bronchial epithelial cell line (BEAS-2B) in a coculture system. Our results demonstrated that the bactericidal effect of bacteriophage could be augmented in the presence of non-mucus-producing epithelial cells (by 3 – 5 log). Adsorption study indicated that both phages and bacteria could adhere to the epithelial cells, subsequently promoting their contact and the phage lytic effect. The presence of epithelial cells could also effectively inhibit/delay the emergence of phage resistance. These findings suggested that evaluating the in vitro antibacterial efficiency of bacteriophage in the presence of mammalian cells may yield better predictions of the therapeutic outcomes of bacteriophage therapy.

Genomic and biological characterization of bacteriophages against Enterobacter cloacae, a high-priority pathogen

Enterobacter cloacae is a clinically significant pathogen due to its multi-resistance to antibiotics, presenting a challenge in the treatment of infections. As concerns over antibiotic resistance escalate, novel therapeutic approaches have been explored. Bacteriophages, characterized by their remarkable specificity and ability to self-replicate within target bacteria, are emerging as a promising alternative therapy. In this study, we isolated and partially characterized nine lytic bacteriophages targeting E. cloacae, with two selected for comprehensive genomic analysis based on their host range and bacteriolytic activity. All identified phages exhibited a narrow host range, demonstrated stability within a temperature range of 30–60 °C, displayed pH tolerance from 3 to 10, and showed an excellent bacteriolytic capacity for up to 18 h. Notably, the fully characterized phage genomes revealed an absence of lysogenic, virulence, or antibiotic-resistance genes, positioning them as promising candidates for therapeutic intervention against E. cloacae-related diseases. Nonetheless, translating this knowledge into practical therapeutic applications mandates a deeper understanding of bacteriophage interactions within complex biological environments.

Targeted deletion of Pf prophages from diverse Pseudomonas aeruginosa isolates has differential impacts on quorum sensing and virulence traits.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that commonly causes medical hardware, wound, and respiratory infections. Temperate filamentous Pf phages that infect P. aeruginosa impact numerous virulence phenotypes. Most work on Pf phages has focused on Pf4 and its host P. aeruginosa PAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf phages infecting P. aeruginosa clinical isolates. We describe a simple technique targeting the Pf lysogeny maintenance gene, pflM (PA0718), that enables the effective elimination of Pf prophages from diverse P. aeruginosa hosts. The pflM gene shows diversity among different Pf phage isolates; however, all examined pflM alleles encode the DUF5447 domain. We demonstrate that pflM deletion results in prophage excision but not replication, leading to total prophage loss, indicating a role for lysis/lysogeny decisions for the DUF5447 domain. This study also assesses the effects different Pf phages have on host quorum sensing, biofilm formation, pigment production, and virulence against the bacterivorous nematode Caenorhabditis elegans. We find that Pf phages have strain-specific impacts on quorum sensing and biofilm formation, but nearly all suppress pigment production and increase C. elegans avoidance behavior. Collectively, this research not only introduces a valuable tool for Pf prophage elimination from diverse P. aeruginosa isolates but also advances our understanding of the complex relationship between P. aeruginosa and filamentous Pf phages.IMPORTANCEPseudomonas aeruginosa is an opportunistic bacterial pathogen that is frequently infected by filamentous Pf phages (viruses) that integrate into its chromosome, affecting behavior. Although prior work has focused on Pf4 and PAO1, this study investigates diverse Pf in clinical isolates. A simple method targeting the deletion of the Pf lysogeny maintenance gene pflM (PA0718) effectively eliminates Pf prophages from clinical isolates. The research evaluates the impact Pf prophages have on bacterial quorum sensing, biofilm formation, and virulence phenotypes. This work introduces a valuable tool to eliminate Pf prophages from clinical isolates and advances our understanding of P. aeruginosa and filamentous Pf phage interactions.

Impact of lytic phages infecting Salmonella enterica subspecies arizonae on physicochemical and microbiological water quality of the old Port of Bizerte (Tunisia, SW Mediterranean Sea)

Phage therapy is among recent innovative technology to improve wastewater quality. Previous phage studies have focused on the interactions of phages with bacterial host cells or the impact of environmental conditions on phage-host cell dynamics. In this research, we particularly examined the impact of phages on a marine physicochemical and microbiological environmental characteristic. Following three days of incubation, seawaters receiving separately phage fBC-Eco01 (OM272052) and phage PA25, undergone a temperature increase of 1.7 °C and 2.5 °C, respectively. Seawater salinity values saved an increase in conductivity over time that ranged between 51.03 and 53.94 µS and from 51.04 to 53.7 μS for the phage PA25 and the phage fBC-Eco01, respectively. A significant decrease in dissolved oxygen levels of 2,1 mg/L were reported following the addition of both phages PA25 and fBC-Eco01 during three days of incubation, compared to a decrease of 1 mg/L in the control seawaters. The TOC increased from 0.33 ppm to 0.67 ppm in the presence of the PA25 phage and from 0.2 ppm to 1.51 ppm after the addition of the fBC-Eco01 phage, compared to control that saved values decreasing from 0.35 ppm to 0.05 ppm. The absorbance and fluorescence spectrophotometry values were also affected by phages addition. Moreover, phages addition reduced total aerobic mesophilic bacteria (TAMB) and Total aerobic thermophilic bacteria (TATB) abundance, corresponding to a decrease of 2 Ulog and 1 Ulog discharge, respectively following addition of PA25 and 3 Ulog and 2 Ulog discharge, respectively with addition of fBC-Ec01 phage.

Bacteriophage specificity is impacted by interactions between bacteria.

There is significant natural diversity in how many different types of bacteria a bacteriophage can infect, but the mechanisms driving this diversity are unclear. This study uses a combination of mathematical modeling and an in vitro system consisting of Escherichia coli, Salmonella enterica, a T5-like generalist phage, and the specialist phage P22vir to highlight the connection between bacteriophage specificity and interactions between their potential microbial prey. Mathematical modeling suggests that competing bacteria tend to favor generalist bacteriophage, while bacteria that benefit each other tend to favor specialist bacteriophage. Experimental results support this general finding. The experiments also show that the optimal phage strategy is impacted by phage degradation and bacterial physiology. These findings enhance our understanding of how complex microbial communities shape selection on bacteriophage specificity, which may improve our ability to use phage to manage antibiotic-resistant microbial infections.

Diversities and interactions of phages and bacteria in deep-sea sediments as revealed by metagenomics.

Phages are found virtually everywhere, even in extreme environments, and are extremely diverse both in their virion structures and in their genomic content. They are thought to shape the taxonomic and functional composition of microbial communities as well as their stability. A number of studies on laboratory culture and viral metagenomic research provide deeper insights into the abundance, diversity, distribution, and interaction with hosts of phages across a wide range of ecosystems. Although most of these studies focus on easily accessible samples, such as soils, lakes, and shallow oceans, little is known about bathypelagic phages. In this study, through analyzing the 16S rRNA sequencing and viral metagenomic sequencing data of 25 samples collected from five different bathypelagic ecosystems, we detected a high diversity of bacteria and phages, particularly in the cold seep and hydrothermal vent ecosystems, which have stable chemical energy. The relative abundance of phages in these ecosystems was higher than in other three abyssal ecosystems. The low phage/host ratios obtained from host prediction were different from shallow ecosystems and indicated the prevalence of prophages, suggesting the complexity of phage-bacteria interactions in abyssal ecosystems. In the correlation analysis, we revealed several phages-bacteria interaction networks of potential ecological relevance. Our study contributes to a better understanding of the interactions between bathypelagic bacteria and their phages.

Chitosan-based matrix as a carrier for bacteriophages

Wound healing is a dynamic and complex process where infection prevention is essential. Chitosan, thanks to its bactericidal activity against gram-positive and gram-negative bacteria, as well as anti-inflammatory and hemostatic properties, is an excellent candidate to design dressings for difficult-to-heal wound treatment. The great advantage of this biopolymer is its capacity to be chemically modified, which allows for the production of various functional forms, depending on the needs and subsequent use. Moreover, chitosan can be an excellent polymer matrix for bacteriophage (phage) packing as a novel alternative/supportive antibacterial therapy approach. This study is focused on the preparation and characteristics of chitosan-based material in the form of a film with the addition of Pseudomonas lytic phages (KTN4, KT28, and LUZ19), which would exhibit antibacterial activity as a potential dressing that accelerates the wound healing. We investigated the method of producing a polymer based on microcrystalline chitosan (MKCh) to serve as the matrix for phage deposition. We described some important parameters such as average molar mass, swelling capacity, surface morphology, phage release profile, and antibacterial activity tested in the Pseudomonas aeruginosa bacterial model. The chitosan polysaccharide turned out to interact with phage particles immobilizing them within a material matrix. Nevertheless, with the high hydrophilicity and swelling features of the prepared material, the external solution of bacterial culture was absorbed and phages went in direct contact with bacteria causing their lysis in the polymer matrix.Key points• A novel chitosan-based matrix with the addition of active phages was prepared• Phage interactions with the chitosan matrix were determined as electrostatic• Phages in the matrix work through direct contact with the bacterial cells

A unified compendium of prokaryotic and viral genomes from over 300 anaerobic digestion microbiomes

BackgroundThe anaerobic digestion process degrades organic matter into simpler compounds and occurs in strictly anaerobic and microaerophilic environments. The process is carried out by a diverse community of microorganisms where each species has a unique role and it has relevant biotechnological applications since it is used for biogas production. Some aspects of the microbiome, including its interaction with phages, remains still unclear: a better comprehension of the community composition and role of each species is crucial for a cured understanding of the carbon cycle in anaerobic systems and improving biogas production.ResultsThe primary objective of this study was to expand our understanding on the anaerobic digestion microbiome by jointly analyzing its prokaryotic and viral components. By integrating 192 additional datasets into a previous metagenomic database, the binning process generated 11,831 metagenome-assembled genomes from 314 metagenome samples published between 2014 and 2022, belonging to 4,568 non-redundant species based on ANI calculation and quality verification. CRISPR analysis on these genomes identified 76 archaeal genomes with active phage interactions. Moreover, single-nucleotide variants further pointed to archaea as the most critical members of the community. Among the MAGs, two methanogenic archaea, Methanothrix sp. 43zhSC_152 and Methanoculleus sp. 52maCN_3230, had the highest number of SNVs, with the latter having almost double the density of most other MAGs.ConclusionsThis study offers a more comprehensive understanding of microbial community structures that thrive at different temperatures. The findings revealed that the fraction of archaeal species characterized at the genome level and reported in public databases is higher than that of bacteria, although still quite limited. The identification of shared spacers between phages and microbes implies a history of phage-bacterial interactions, and specifically lysogenic infections. A significant number of SNVs were identified, primarily comprising synonymous and nonsynonymous variants. Together, the findings indicate that methanogenic archaea are subject to intense selective pressure and suggest that genomic variants play a critical role in the anaerobic digestion process. Overall, this study provides a more balanced and diverse representation of the anaerobic digestion microbiota in terms of geographic location, temperature range and feedstock utilization.

Surface-enhanced Raman spectroscopy for the characterization of bacterial pellets of Staphylococcus aureus infected by bacteriophage.

Drug-resistant pathogenic bacteria are a major cause of infectious diseases in the world and they have become a major threat through the reduced efficacy of developed antibiotics. This issue can be addressed by using bacteriophages, which can kill lethal bacteria and prevent them from causing infections. Surface-enhanced Raman spectroscopy (SERS) is a promising technique for studying the degradation of infectious bacteria by the interaction of bacteriophages to break the vicious cycle of drug-resistant bacteria and help to develop chemotherapy-independent remedial strategies. The phage (viruses)-sensitive Staphylococcus aureus (S. aureus) bacteria are exposed to bacteriophages (Siphoviridae family) in the time frame from 0 min (control) to 50 minutes with intervals of 5 minutes and characterized by SERS using silver nanoparticles as SERS substrate. This allows us to explore the effects of the bacteriophages against lethal bacteria (S. aureus) at different time intervals. The differentiating SERS bands are observed at 575 (C-C skeletal mode), 620 (phenylalanine), 649 (tyrosine, guanine (ring breathing)), 657 (guanine (COO deformation)), 728-735 (adenine, glycosidic ring mode), 796 (tyrosine (C-N stretching)), 957 (C-N stretching (amide lipopolysaccharides)), 1096 (PO2 (nucleic acid)), 1113 (phenylalanine), 1249 (CH2 of amide III, N-H bending and C-O stretching (amide III)), 1273 (CH2, N-H, C-N, amide III), 1331 (C-N stretching mode of adenine), 1373 (in nucleic acids (ring breathing modes of the DNA/RNA bases)) and 1454 cm-1 (CH2 deformation of saturated lipids), indicating the degradation of bacteria and replication of bacteriophages. Multivariate data analysis was performed by employing principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to study the biochemical differences in the S. aureus bacteria infected by the bacteriophage. The SERS spectral data sets were successfully differentiated by PLS-DA with 94.47% sensitivity, 98.61% specificity, 94.44% precision, 98.88% accuracy and 81.06% area under the curve (AUC), which shows that at 50 min interval S. aureus bacteria is degraded by the replicating bacteriophages.

Chemical inhibition of cell surface modification sensitizes bacteria to phage infection.

Many bacteriophages that infect Gram-positive bacteria rely on the bacterial cell surface polymer wall teichoic acid (WTA) as a receptor. However, some bacteria modulate their cell wall with d-alanine residues, which can disrupt phage adsorption. The prevalence and significance of WTA alanylation as an anti-phage defense is unknown. A chemical inhibitor of WTA d-alanylation could be employed to efficiently screen phage-host combinations for those that exhibit alanylation-dependent infections. Since the incorporation of d-alanine residues into the cell wall requires the activity of d-alanine:alanyl carrier protein ligase (DltA), a DltA inhibitor was employed as this tool. Herein, we found that a chemical probe inhibiting DltA activity impeded bacterial cell wall alanylation and enhanced infectivity of many phages against Bacillus subtilis, including phages Phi29, SPP1, SPO1, SP50, and Goe2. This finding reveals the breadth of immunity conferred by WTA alanylation in B. subtilis, which was previously known to impact only phages Phi29 and SPP1, but not SPO1, SP50, or Goe2. DltA inhibition selectively promoted infection by several phages that bind WTA, having no impact on the flagellotropic phage PBS1. Unexpectedly, DltA inhibition also had no effect on phage SP10, which binds to WTA. This selective chemical tool has the potential to unravel bacteriophage interactions with bacteria, leading to improved phage therapies in the future.

Interaction of Bacteriophages with the Immune System: Induction of Bacteriophage-Specific Antibodies.

In all cases when a bacteriophage makes a direct contact with a mammalian organism, it may challenge the mammalian immunological system. Its major consequence is the production of antibodies specific to the bacteriophage, particularly IgM, IgG, and IgA as the typical response. Here we present protocols applicable in studies of the ability of bacteriophage to induce specific antibodies; immunization to whole virions or to isolated phage proteins has been included. The protocols have been divided into three parts: purification, immunization, and detection (enzyme-linked immunosorbent assay, ELISA).

The use of plant extracts and bacteriophages as an alternative therapy approach in combatting bacterial infections: the study of lytic phages and Stevia rebaudiana.

In the light of the problem of antibiotic resistance, the use of combined alternative therapies in combatting bacteria-related disorders has gained popularity. Bacteriophages are one element implemented in new combination therapy. Stevia rebaudiana is known to have antimicrobial activity and regarded as potentially having a synergistic effect with bacteriophages. Therefore, possible interactions of lytic bacteriophages (MS2, T4 and Phi6) with acetone and methanol S. rebaudiana extracts (SRa and SRm) in the bacterial environment were examined. The interactions were tested using a microdilution method, phage-extract co-incubation assay, static interaction (synography) and dynamic growth profile experiments in a bioreactor. The interactions of the tested factors in a static environment differed from those in a dynamic environment. Dynamic conditions altered the effect of the extracts in a concentration-dependent manner. How different the effect of the SRa extract was to that of the SRm extract on bacterial growth in a dynamic environment depended on the species of the phage and bacterial host. The greatest differences were observed for E. coli strains and their phages, whereas Pseudomonas syringae and the Phi6 phage reacted very similarly to both extracts. Differences also emerged for the same extract in different E. coli strains and their phages. Every extract type should be tested on a case-by-case basis and experiment outcomes should not be generalised before gathering data. Moreover, many varied experiments should be performed, especially when examining such multifactorial mixtures. The tested mixtures could potentially be used in multidrug-resistant bacterial infection treatments.

Basic Guidelines for Bacteriophage Isolation and Characterization.

The world is on the cusp of a post-antibiotic period. A century ago, before the advent of antibiotics, bacteriophage therapy was the treatment of choice for bacterial infections. Although bacteriophages have yet to be approved as a treatment in Western medicine, researchers and clinicians have begun to anticipate phage therapy. Bacteriophages are viruses that depend on bacterial cell metabolism to multiply. They offer a promising alternative to the use of antibiotics and an excellent antibacterial option for combating multidrug resistance in bacteria. However, not every phage is suitable for phage therapy. In particular, prophages should not be used because they can lysogenize host cells instead of lysing them. To offer adequate therapeutic options for patients suffering from various infectious diseases, a wide selection of different phages is needed. While there is no evidence of direct toxicity induced by phage particles, it is crucial to study mammalian cell-phage interactions. This requires phage preparations to be free of bacterial cells, toxins and other compounds to avoid skewing host responses. Negative staining of purified viruses and electron microscopy remain the gold standard in the identification of bacteriophages. Interestingly, genomics has greatly changed our understanding of phage biology. Bacteriophage genome sequencing is essential to obtain a complete understanding of the bacteriophages' biology and to obtain confirmation of their lifestyle. Full genetic sequencing of bacteriophage will enable a better understanding of the phage-encoded proteins and biomolecules (especially phage lytic enzymes) involved in the process of bacterial cell lysis and death. Mass spectrometry can be used for the identification of phage structural proteins. The use of lytic phages as biocontrol agents requires the most appropriate and standard methods to ensure application safety. This review pursues recent research and methods in molecular biology for the isolation and characterization of phages to facilitate follow-up and implementation of work for other researchers. Patents related to this topic have been mentioned in the text.

The Role of Bacteriophages in the Gut Microbiota: Implications for Human Health.

Bacteriophages (phages) are nano-sized viruses characterized by their inherent ability to live off bacteria. They utilize diverse mechanisms to absorb and gain entry into the bacterial cell wall via the release of viral genetic material, which uses the replication mechanisms of the host bacteria to produce and release daughter progeny virions that attack the surrounding host cells. They possess specific characteristics, including specificity for particular or closely related bacterial species. They have many applications, including as potential alternatives to antibiotics against multi-resistant bacterial pathogens and as control agents in bacteria-contaminated environments. They are ubiquitously abundant in nature and have diverse biota, including in the gut. Gut microbiota describes the community and interactions of microorganisms within the intestine. As with bacteria, parasitic bacteriophages constantly interact with the host bacterial cells within the gut system and have obvious implications for human health. However, it is imperative to understand these interactions as they open up possible applicable techniques to control gut-implicated bacterial diseases. Thus, this review aims to explore the interactions of bacteriophages with bacterial communities in the gut and their current and potential impacts on human health.