Method of treating microbial infections
Inventors
Gallo, Richard L. • Nakatsuji, Teruaki
Assignees
Office of General Counsel of VA • University of California San Diego UCSD
Publication Number
US-10085997-B2
Publication Date
2018-10-02
Expiration Date
2032-02-14
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Abstract
The disclosure provides for novel antimicrobial agents, methods of making, and methods of use thereof.
Core Innovation
The invention provides novel antimicrobial agents derived from the culture supernatant of Staphylococcus epidermidis strain MO34, methods of preparing these agents, and their applications in treating microbial infections. The core innovation includes the isolation and purification of a novel compound referred to as "firmocidin," which has a molecular formula of C5H5N5O and exhibits selective antimicrobial activity against common skin pathogens such as Group A Streptococcus (GAS), Group B Streptococcus (GBS), Staphylococcus aureus including methicillin-resistant strains (MRSA), while sparing Staphylococcus epidermidis, a normal skin commensal.
The method of purifying firmocidin involves culturing S. epidermidis MO34, isolating the culture supernatant by filtration (0.2 μm filter), and further purification by high-performance liquid chromatography (HPLC) using a TaskGel NH2-100 column with a gradient elution. Firmocidin does not match any previously known antimicrobial agents based on NMR and mass spectrometry analysis, indicating its novelty. Its antimicrobial activity is stronger than commonly used topical agents such as benzoyl peroxide and is not cytotoxic to human keratinocytes and sebocytes, suggesting suitability for safe topical use.
The problem being solved is the widespread increase of antibiotic-resistant microbial infections, especially skin-related infections caused by prevalently resistant strains of Staphylococcus aureus such as MRSA. Existing antibiotic therapies often lack specificity, disrupting beneficial skin microflora and potentially contributing to further resistance development. Moreover, current antibiotics have limitations including toxicity, broad-spectrum killing that harms normal flora, cross-resistance, and high costs of newer agents. There is an unmet need for pathogen-specific antimicrobial agents that are effective against resistant strains, safe for the host, and preserve the normal skin microbial balance.
Claims Coverage
The patent contains multiple claims encompassing compositions, methods of preparation, and methods of inhibiting skin pathogens using antimicrobial compositions derived from Staphylococcus epidermidis strain MO34. The independent claims focus on the purified supernatant and its antimicrobial use.
Composition comprising purified culture supernatant of Staphylococcus epidermidis strain MO34
A composition comprising a supernatant obtained by filtering a culture of Staphylococcus epidermidis strain MO34 through a 0.2 µm filter, optionally dried under vacuum and formulated for topical administration in various forms including liposomes, lotions, creams, soaps, emulsions, gels, sprays, ointments, and patches.
Method of making the antimicrobial composition
A method comprising culturing Staphylococcus epidermidis strain MO34 in a culture medium such as tryptic soy broth, isolating the culture supernatant by filtration (0.2 µm filter or 3 kDa cutoff), and lyophilizing the supernatant to obtain the antimicrobial composition.
Method of inhibiting skin pathogens by contacting with the antimicrobial composition
A method of inhibiting a broad range of skin pathogens including gram-positive and gram-negative bacteria, fungi, and yeasts by contacting the pathogens with the purified culture supernatant composition derived from Staphylococcus epidermidis strain MO34. The pathogens include but are not limited to Staphylococcus aureus, Streptococcus pyogenes (group A), Streptococcus agalactiae (group B), various other bacteria, Microsporum, Trichophyton species, Candida species, Aspergillus species, and others.
The independent claims cover the purified antimicrobial composition derived from S. epidermidis strain MO34, the methods of culturing and purifying this composition, and its use in inhibiting a wide range of skin pathogens effectively and safely.
Stated Advantages
Firmocidin exhibits pathogen-specific antimicrobial activity against resistant and common skin pathogens including MRSA while sparing beneficial skin microflora such as S. epidermidis.
Firmocidin has stronger antimicrobial activity in vitro than benzoyl peroxide, a commonly used topical medication.
Firmocidin is not cytotoxic to human keratinocytes and sebocytes, indicating safety for topical applications.
Firmocidin is derived from a microorganism residing in the normal skin microflora, suggesting low host toxicity and preservation of skin homeostasis.
The methods and compositions provide a novel approach to control skin infections caused by antibiotic-resistant and common pathogens, potentially overcoming resistance and toxicity issues with existing antibiotics.
Documented Applications
Treatment of skin infections caused by bacteria including methicillin-resistant Staphylococcus aureus (MRSA), Group A streptococcus (GAS), Group B streptococcus (GBS), and Staphylococcus aureus.
Treatment of fungal infections caused by species such as Microsporum sp., Trichophyton sp., Candida albicans, Aspergillus sp., and others.
Use as a topical antimicrobial agent formulated in creams, ointments, gels, lotions, sprays, and other topical dosage forms for controlling skin pathogens while preserving normal skin flora.
Use in combination with other antibiotics or antimicrobial agents to treat various bacterial, fungal, viral, or parasitic infections.
Potential application in treatment or prevention of dermatological disorders including wounds, diabetic ulcers, acne, rosacea, atopic dermatitis, pyodermas, and burn wounds.
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