Bacteriophage compositions and methods for treatment of bacterial infections
Inventors
Maresso, Anthony • Ramig, Robert • Green, Sabrina • Terwilliger, Austen • Salazar, Keiko • Clark, Justin R. • Trautner, Barbara
Assignees
Baylor College of Medicine • US Department of Veterans Affairs
Publication Number
US-12274723-B2
Publication Date
2025-04-15
Expiration Date
2042-12-05
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Abstract
Disclosed are compositions, devices, kits, and methods for treatment of Enterobacteriaceae infection. Aspects of the present disclosure are directed to bacteriophage compositions comprising one or more of ES17, ES19, HP3, HP3.1, and HP3.2. Certain aspects of the disclosure are directed to compositions comprising (a) bacteriophage ES17 or bacteriophage ES19, (b) bacteriophage HP3, and (c) bacteriophage HP3.1. Also disclosed are compositions comprising bacteriophage HP 3.2. Further disclosed are devices and kits comprising such compositions and methods for use of such compositions in treatment and prevention of pathogenic E. coli infection.
Core Innovation
Aspects of the present disclosure are directed to bacteriophage compositions comprising one or more of bacteriophages ES17, ES19, HP3, HP3.1, and HP3.2 for treatment and prevention of Enterobacteriaceae infections, specifically pathogenic and multidrug-resistant (MDR) Escherichia coli (E. coli) infections, including extraintestinal pathogenic E. coli (ExPEC). The compositions may also include metals and pharmaceutically acceptable excipients and can be provided in various formulations or housed in delivery devices. Methods are disclosed for administering these compositions to individuals to treat or prevent E. coli infections, as well as devices and kits incorporating such bacteriophage compositions.
The invention addresses the problem that multidrug-resistant (MDR) bacteria, especially Enterobacteriaceae such as ExPEC strains of E. coli, pose an urgent threat due to their resistance to antibiotics, making infections untreatable. Existing antibiotic development is slow and resistance rapidly emerges. Bacteriophage (phage) therapy is a promising alternative due to phage specificity and ability to infect MDR bacteria but is limited by environmental factors such as mucins in the gastrointestinal tract that inhibit phage activity, and by development of phage-resistant bacterial strains. There is a need for new and improved bacteriophage compositions and methods capable of overcoming these challenges to effectively treat or prevent bacterial infections including MDR E. coli.
The disclosure specifically solves the problem of phage inhibition by mucin present in intestinal environments by identifying and employing phage ES17, which uniquely binds mucin and mammalian heparan sulfated proteoglycans to locate bacterial hosts more effectively in mucin-rich environments. It also addresses the frequent emergence of phage-resistant bacteria by evolving phage HP3 into derivatives HP3.1 and HP3.2 that can overcome such resistance. These phages and their combinations demonstrate enhanced efficacy in vivo and in vitro in treating E. coli infections, including in complex environments like the mammalian intestine and bloodstream, thereby providing compositions and methods suitable for effective therapeutic use.
Claims Coverage
The patent document includes two independent claims focusing on compositions comprising bacteriophage HP3.2 and bacteriophage HP3.1, as well as methods and devices comprising these compositions. The main inventive features relate to phage compositions, associated devices, and methods for treating E. coli infections.
Composition comprising bacteriophage HP3.2
Discloses a composition comprising bacteriophage HP3.2 optionally combined with one or more metals such as calcium, magnesium, iron, sodium, and potassium. The composition can be provided in liquid or solid formulation and housed within a delivery apparatus.
Medical device incorporating bacteriophage HP3.2 composition
A device such as a catheter, implant, or stent comprising the bacteriophage HP3.2 composition on, in, or around the device, including devices further defined as coated with the bacteriophage composition.
Method of treating or preventing E. coli infection with HP3.2 composition
A method of administering a therapeutically effective amount of the bacteriophage HP3.2 composition to an individual to treat or prevent an E. coli infection. Administration routes include intravenous, oral, or administration on a device, with dosing regimens ranging from once to multiple times per day, week, or month for periods from weeks to months.
Composition comprising bacteriophage HP3.1 with metals
A composition including bacteriophage HP3.1 and one or more metals serving as additional components.
Medical device incorporating bacteriophage HP3.1 composition
A device such as those described for HP3.2 incorporating a composition comprising bacteriophage HP3.1 on, in, or around the device.
Method of treating or preventing E. coli infection with HP3.1 composition
A method of administering a therapeutically effective amount of a composition comprising bacteriophage HP3.1 to an individual for treatment or prevention of E. coli infections, including multidrug-resistant or extraintestinal pathogenic strains, using intravenous, oral, or device-based administration.
The claims cover compositions specifically comprising bacteriophages HP3.2 and HP3.1 optionally combined with metals, medical devices incorporating these compositions, and methods of treating or preventing E. coli infections by administering these compositions via various routes and dosing regimens. The inventive features focus on use of these bacteriophages in compositions, devices, and therapeutic methods aimed at combating pathogenic E. coli infections.
Stated Advantages
The compositions comprising bacteriophage ES17 demonstrate enhanced ability to lyse pathogenic E. coli in mucin-rich intestinal environments, overcoming the inhibitory effect of intestinal mucins.
The evolved bacteriophages HP3.1 and HP3.2 are capable of overcoming bacterial resistance developed against the original phage HP3, improving efficacy against multidrug-resistant E. coli strains.
Phage compositions and cocktails provide effective reduction or elimination of pathogenic E. coli in complex biological environments including the intestine and organs affected in bacteremia.
Devices coated or containing the bacteriophage compositions can prevent or treat infections associated with indwelling medical devices, such as catheters and implants.
Documented Applications
Treatment or prevention of infections caused by pathogenic E. coli, including multidrug-resistant and extraintestinal pathogenic strains, in humans and non-humans.
Therapy for infections in various body sites including urinary tract, blood, gut, abdomen, stomach, lungs, skin, kidneys, prostate, bladder, brain, vaginal tract, heart, liver, and spleen.
Treatment or prevention of catheter-associated urinary tract infections and infections associated with other implanted or inserted medical devices.
Use in immunosuppressed individuals including those undergoing chemotherapy or immunosuppressive treatments, to reduce risk or severity of E. coli infections.
Coating of medical devices to inhibit bacterial colonization and biofilm formation, thereby preventing device-associated infections.
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