Did you know?
Phages are the most abundant biological entities on Earth, with an estimated 10^31 phages in the biosphere! That’s more phages than every other organism on the planet combined—including bacteria, plants, and animals.
Phage Therapy
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Phage therapy uses viruses to target and kill specific bacteria, offering a precise alternative to antibiotics, especially for resistant infections.
Research feed -
Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
FAQs 
Research Feed 
References Overview
Phage therapy is a targeted therapeutic approach that utilizes bacteriophages (or simply “phages”)—viruses that infect and lyse specific bacterial cells—to combat bacterial infections. This method is gaining renewed interest, especially in the context of rising antibiotic resistance, due to its ability to selectively target pathogenic bacteria while sparing the host’s normal microbiota.
Mechanism of Action
Phages operate by binding to specific receptors on the surface of their target bacterial host. Once attached, the phage injects its genetic material into the bacterium, hijacking the host’s machinery to produce more phage particles. This process culminates in bacterial lysis, releasing new phages to infect additional bacterial cells.
Key Characteristics of Phage Therapy
Phage therapy offers a highly specific, self-regulating, and targeted approach to bacterial infections, making it an ideal candidate for precision medicine. Unlike broad-spectrum antibiotics, bacteriophages can be tailored to selectively eliminate pathogenic bacteria without disrupting beneficial commensal flora, thereby reducing the risk of dysbiosis. Their natural diversity allows for the isolation of phages that target drug-resistant or particularly virulent strains, offering therapeutic options where conventional antibiotics fail. Moreover, phages replicate only in the presence of their bacterial host, making them inherently self-limiting and minimizing the risk of overtreatment or systemic toxicity. A particularly compelling advantage of phage therapy is its ability to penetrate and disrupt biofilms—dense microbial communities that are often recalcitrant to antibiotic treatment. This property positions phage therapy as a promising intervention for chronic, biofilm-associated infections such as those seen in cystic fibrosis, prosthetic joint infections, and diabetic ulcers.
Clinical Applications
Antibiotic resistance limits the effectiveness of conventional treatments. In chronic wound infections, phages targeting Pseudomonas aeruginosa and Staphylococcus aureus have shown promise in promoting healing when standard antibiotics are ineffective. In respiratory tract infections, particularly in cystic fibrosis patients, phage therapy has been investigated as a means to reduce bacterial load and disrupt biofilms formed by Pseudomonas species, which are notoriously resistant to treatment. Moreover, phage cocktails have been employed under compassionate use protocols to treat multidrug-resistant (MDR) infections caused by pathogens such as Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. In several of these cases, clinical improvement has been observed after the failure of traditional antimicrobial therapies, underscoring phage therapy’s potential as a precision tool in the fight against antimicrobial resistance. [1]
Phage Cocktails and Customization
Given that bacterial resistance to individual phages can emerge, phage therapy commonly employs phage cocktails—combinations of multiple bacteriophages designed to target the same or a range of bacterial strains. This approach reduces the likelihood of resistance development while expanding antimicrobial coverage and improving clinical efficacy. Phage cocktails can be strategically customized in two key ways. First, by analyzing microbial resistance profiles and identifying Major Microbial Associations (MMAs) within a patient’s microbiome, clinicians can select phages that specifically target the most pathogenic or overrepresented taxa. Second, in personalized medicine contexts, phage cocktails can be tailored to individual patients by isolating phages that are active against the specific bacterial strains present in their infection. This allows for a precision-targeted intervention that maximizes therapeutic impact while minimizing disruption to commensal microbial communities.
Considerations for Phage Therapy
Phage therapy remains largely in the experimental and compassionate use stages across many countries, with ongoing clinical trials evaluating its efficacy, safety, and standardization. Key challenges include ensuring phage stability during storage and delivery—whether topical, oral, or intravenous—as viability is essential for therapeutic effect. Regulatory and manufacturing hurdles also persist, particularly in the consistent production of phage cocktails that meet safety and quality standards. Additionally, the host immune system may recognize and neutralize phages, especially with systemic administration, potentially reducing their effectiveness over repeated dosing or long-term use.
Phage Therapy vs. Antibiotics
While antibiotics remain the cornerstone of bacterial infection treatment, phage therapy presents several distinct advantages—especially in the context of rising antibiotic resistance. One key benefit is the reduced resistance pressure phages exert on microbial communities; their high specificity limits off-target effects, thereby minimizing the selection of resistant strains among commensal or unrelated bacteria. Additionally, phage therapy holds strong potential for co-therapy applications. When used alongside antibiotics, phages can act synergistically due to their distinct mechanisms of action, enhancing bacterial clearance and improving outcomes in cases involving multidrug-resistant infections. This complementary approach may also help preserve antibiotic efficacy and reduce treatment failure.
Clinical Outlook
For clinicians, phage therapy represents a promising adjunct or alternative to traditional antibiotics, particularly in the fight against antibiotic-resistant infections. However, patient selection, microbiological diagnosis, microbiome signature consensus, and regulatory hurdles remain key considerations. As research progresses and regulatory pathways become clearer, phage therapy could become a valuable tool in the clinical management of recalcitrant bacterial infections.
FAQs
How do phage cocktails fit into the framework of Microbiome-Targeted Interventions (MBTIs)?
How do phage cocktails fit into the framework of Microbiome-Targeted Interventions (MBTIs)?
Phage cocktails are a form of Microbiome-Targeted Interventions (MBTIs) designed to selectively target and eliminate pathogenic microbes identified as Major Microbial Associations (MMAs) within a disease’s microbiome signature. By harnessing the specificity of phages, phage cocktails can be tailored to attack harmful bacterial strains while preserving beneficial microbes. This precision minimizes collateral damage to the overall microbiome, making phage cocktails a promising intervention for restoring microbial balance in conditions where dysbiosis plays a critical role, such as inflammatory bowel disease (IBD) or chronic wound infections.
How are phage cocktails developed based on the microbiome signature of a specific condition?
How are phage cocktails developed based on the microbiome signature of a specific condition?
Phage cocktails are developed by identifying the MMAs—key pathogenic microbes consistently associated with a disease’s microbiome signature. Through sequencing and metagenomic analysis, these pathogenic microbes are isolated and matched with phages that can specifically lyse them. The cocktail is then formulated to target multiple strains or species of these MMAs, reducing the risk of bacterial resistance and ensuring a comprehensive intervention that aligns with the microbial profile of the condition.
Why are MMAs important in designing personalized phage therapies for specific conditions?
Why are MMAs important in designing personalized phage therapies for specific conditions?
MMAs help clinicians and researchers pinpoint the most relevant bacterial targets for phage therapy in specific diseases. By understanding which microbes drive the pathogenesis of a condition, phage cocktails can be personalized for the patient’s unique microbiome. This precision ensures that phage therapy is not only effective in eliminating the pathogenic microbes involved in the disease but also preserves the beneficial members of the patient’s microbiome, leading to more successful and targeted therapeutic outcomes.
Research Feed
Phage Therapy Against Antibiotic‐Resistant and Multidrug‐Resistant Infections Involving Nonhealing Wounds: A Mini‐Review
This review highlights the safety and efficacy of phage therapy for chronic and prosthetic joint infections, showing a 91% success rate. Targeted pathogens include P. aeruginosa and S. aureus, key MMAs in wound microbiomes, underscoring phages as viable interventions for biofilm-associated, drug-resistant infections.
What Was Reviewed?
This mini-review titled “Phage Therapy Against Antibiotic-Resistant and Multidrug-Resistant Infections Involving Nonhealing Wounds and Prosthetic Joint Infections Associated With Biofilms” evaluates 27 studies published between 2017 and 2023 to determine the efficacy and safety of bacteriophage (phage) therapy in the treatment of chronic wounds (CWs) and prosthetic joint infections (PJIs), particularly those complicated by biofilm formation and antimicrobial resistance. The authors conducted a systematic literature search across PubMed, Web of Science, Cochrane, and ClinicalTrials.gov, yielding 3151 articles, of which 27 met the inclusion criteria, encompassing 130 patients and 152 distinct infections. The review focuses on the types of infections treated, microbial etiologies, therapeutic modalities employed, and clinical outcomes following phage therapy.
Who Was Reviewed?
The reviewed studies involved 130 patients, most of whom were treated for chronic wound infections (n=130 infections) and prosthetic joint infections (n=22 infections). The demographic diversity included cases from the USA, France, Germany, India, Georgia, Australia, Belgium, and Italy. Notably, infections were predominantly caused by Pseudomonas aeruginosa (36.2%) and Staphylococcus aureus (27.0%) in wound cases, and S. aureus (50%) in PJIs. Most of these infections were either antibiotic-resistant or multidrug-resistant (MDR), and 65% of MDR cases were treated with phage cocktails. Treatment modalities varied and included topical, intraarticular, intravenous, or combined applications.
Most Important Findings
Phage therapy achieved an overall success rate of 91%, highlighting its substantial potential in managing nonhealing wounds and PJIs associated with biofilms and antibiotic resistance. The data suggest that P. aeruginosa and S. aureus are major microbial associations (MMAs) in chronic and prosthetic wound infections, reaffirming their significance in dysbiotic microbiomes characterized by biofilm resilience and MDR phenotypes. Topical application was the most frequently employed modality (78.8%), particularly for chronic wounds. Despite differences in phage types, doses (ranging from 10⁶ to 10¹⁰ PFU/mL), and treatment duration (from 1 day to 7 weeks), the outcomes were predominantly favorable.
Importantly, the phages’ ability to disrupt biofilms via depolymerase activity and potentially enhance antibiotic susceptibility suggests a dual benefit in combination therapies. This was indirectly supported by observations that many patients received concurrent antibiotics, indicating possible phage-antibiotic synergy. Adverse effects were minimal, with only 4.6% of patients reporting complications, most commonly transient elevations in liver enzymes (ALT/AST), typically in S. aureus-associated PJIs. There were no serious complications directly attributable to phage therapy.
From a microbiome perspective, the consistent isolation of P. aeruginosa, S. aureus, S. epidermidis, and E. coli across chronic wound and prosthetic joint infections suggests a stable core dysbiosis pattern across these pathologies. These organisms are known for their biofilm-forming capacity and resistance mechanisms, reinforcing their designation as MMAs in wound microbiome dysbiosis. The successful targeting of these taxa using phage cocktails validates the role of phage therapy as a precision intervention to address microbial imbalances and resistant infections.
Greatest Implications
The review underscores phage therapy’s clinical viability as a microbiome-targeted strategy for managing MDR infections involving MMAs like P. aeruginosa and S. aureus, especially when biofilms are implicated. The ability to bypass traditional resistance mechanisms, dismantle biofilm matrices, and reduce persister cell populations positions phage therapy as a transformative adjunct or alternative to antibiotics. For microbiome-focused clinicians, these findings validate the consideration of phage therapy in cases where the pathogen composition is known and aligns with established MMAs. Moreover, the minimal adverse effects and high success rate justify expanded clinical trials and standardized dosing protocols, particularly for microbiome-restorative therapeutic frameworks.
Escherichia coli (E. coli)
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Major Microbial Associations (MMAs)
Major Microbial Associations (MMAs) are fundamental in understanding disease-microbiome interactions and play a crucial role in advancing microbiome-targeted interventions aimed at treating or preventing diseases through microbial modulation.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
References
- Bacteriophage Therapy of Chronic Nonhealing Wound: Clinical Study.. Gupta P, Singh HS, Shukla VK, Nath G, Bhartiya SK.. (Int J Low Extrem Wounds. 2019)
Gupta P, Singh HS, Shukla VK, Nath G, Bhartiya SK.
Bacteriophage Therapy of Chronic Nonhealing Wound: Clinical Study.Int J Low Extrem Wounds. 2019