Compositions and methods for treating antibiotic resistance
Inventors
FORD, Christopher Burton • BRYANT, Jessica • O'Brien, Edward J.
Assignees
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Publication Number
US-12214002-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The present invention relates to compositions and methods for reducing the carriage of antibiotic resistance genes.
Core Innovation
The invention provides ROAR (reduction of antibiotic resistance) compositions and methods that reduce the abundance of antibiotic-resistance genes in the microbiome of a mammalian subject. The composition comprises a combination of bacteria including Blautia wexlerae and Anaerotruncus colihominis, administered as a therapeutically effective amount to produce a reduction in antibiotic-resistance gene abundance after administration.
The methods address antibiotic-resistance genes that confer resistance to beta-lactam antibiotics and at least one additional antibiotic drug class. In a treating context, the subject is at risk for or diagnosed with an undesirable level of bacteria that are resistant to multiple antibiotic drug classes, where the undesirable level is significantly greater than that in a healthy subject population.
Blautia wexlerae is defined by a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255, and Anaerotruncus colihominis is defined by a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92. The documented content further connects administration with changes in gut resistome gene abundance and includes analysis tied to resistance gene markers and drug classes, including findings that engraftment of administered spores is associated with decreased antibiotic-resistance gene abundance.
Claims Coverage
The independent claims cover two method categories: reducing the abundance of at least one antibiotic-resistance gene in the microbiome of a mammalian subject, and treating a mammalian subject at risk for or diagnosed with an undesirable level of bacteria resistant to multiple antibiotic drug classes. Each independent claim centers on administering a therapeutically effective composition that combines Blautia wexlerae and Anaerotruncus colihominis, with both bacteria defined by specific 16S rDNA identity thresholds to specified SEQ ID NOs.
Combination of Blautia wexlerae and Anaerotruncus colihominis for microbiome reduction or treatment
Administering to a mammalian subject a therapeutically effective amount of a composition comprising a combination of bacteria comprising Blautia wexlerae and Anaerotruncus colihominis.
Reducing antibiotic-resistance gene abundance with beta-lactam and additional drug class resistance
After administration, the abundance of at least one antibiotic-resistance gene in the microbiome of the subject is reduced as compared to a corresponding subject who did not receive the administration, wherein the at least one antibiotic-resistance gene is capable of conferring resistance to beta-lactam antibiotics and at least one additional antibiotic drug class.
Treatment of multi-drug-class resistant bacteria at risk or diagnosed with undesirable level
Treating a mammalian subject at risk for or diagnosed with an undesirable level of bacteria that are resistant to multiple antibiotic drug classes, wherein the undesirable level is significantly greater than that in a healthy subject population, and wherein the multiple antibiotic drug classes comprise beta-lactam antibiotics and at least one additional antibiotic drug class.
16S rDNA identity-defined Blautia wexlerae
Blautia wexlerae comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255.
16S rDNA identity-defined Anaerotruncus colihominis
Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.
Across the independent claims, the core inventive structure is a therapeutically effective composition containing a defined combination of Blautia wexlerae and Anaerotruncus colihominis, where each species is defined by 16S rDNA sequence identity of at least 97% to specified SEQ ID NO reference sequences. The claimed outcomes are reduction in the abundance of at least one antibiotic-resistance gene in a mammalian microbiome or treatment of subjects with an undesirable level of bacteria resistant to multiple antibiotic drug classes.
Stated Advantages
Reduces the abundance of at least one antibiotic-resistance gene in the microbiome of the subject compared to a corresponding subject who did not receive the administration.
Supports treatment of a mammalian subject at risk for or diagnosed with an undesirable level of bacteria that are resistant to multiple antibiotic drug classes, compared to a healthy subject population baseline.
Treats a mammalian subject at risk for or diagnosed with an undesirable level of bacteria resistant to multiple antibiotic drug classes.
Documented Applications
Reducing gut resistome antibiotic-resistance gene abundance in a mammalian gastrointestinal microbiome, including reduction across beta-lactam antibiotics and additional antibiotic drug classes.
Reducing an abundance of at least one antibiotic-resistance gene in the microbiome of a mammalian subject in need thereof.
Treating a mammalian subject at risk for or diagnosed with an undesirable level of bacteria resistant to multiple antibiotic drug classes.
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