Bacterial biofilms and cancer

Abstract

Compositions for the treatment of colorectal cancer target bacterial biofilms in the gastrointestinal tract. Methods of treatment include one or more agents which target bacteria and the bacterial biofilms.

1 . A method of treating cancer in a subject, comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from  Bacteroides  and at least one bacterial type from Enterobacteriaceae; thereby treating the subject. 
     
     
         2 . The method of  claim 2 , wherein the one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria comprise antibacterial agents, antibiotics, probiotics, mucosal protective agents, adjuvants, vaccines, antibodies, small molecule inhibitors, mucosal antigen specific immune cell modulating agents, anti-inflammatory agents, anti-cytokine agents, cytokines, antigen presenting cells, small molecule compounds, small molecule inhibitors of toxins, antisense oligonucleotides, antibiotics, species-specific bacteriophages, toxins, membrane destabilizing agents, antibacterial or antimicrobial compounds, siRNA reagents, antibodies, antibody fragments bearing epitope recognition sites, such as Fab, Fab′, F(ab′) 2  fragments, Fv fragments, single chain antibodies, antibody mimetics (such as DARPins, affibody molecules, affilins, affitins, anticalins, avimers, fynomers, Kunitz domain peptides and monobodies), peptoids, aptamers; cytokines, cellular factors, enzymes, immune cell modulating agents, adoptive cell therapeutics, peptides, organic or inorganic molecules, natural or synthetic compounds, or combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the at least one bacterial type from  Bacteroides  is enterotoxigenic  Bacteroides fragilis  (ETBF) and the at least one bacterial type from Enterobacteriaceae is  Escherichia coli  ( E. coli ). 
     
     
         4 . The method of  claim 3 , wherein the  E. coli  comprise polyketide synthase (pks) genes. 
     
     
         5 . The method of  claim 3 , wherein the  E. coli  encode or express a colibactin genotoxin. 
     
     
         6 . The method of  claim 3 , wherein the enterotoxigenic  Bacteroides fragilis  (ETBF) encode or express a  Bacteroides fragilis  toxin (bft). 
     
     
         7 . The method of  claim 1 , wherein the ETBF and  E. coli  co-colonize the subject's gastrointestinal tract. 
     
     
         8 . The method of  claim 2 , wherein the one or more antibiotics comprise: clindamycin, beta-lactams, macrolides, chloramphenicol, aminoglycosides, fluoroquinolones, carbapenems, sulbactam or combinations thereof. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 2 , wherein the administered one or more agents are B-cell activating factor (BAFF), cytokines, adjuvants, immunogens, peptides, vectors expressing one or more peptides, or combinations thereof. 
     
     
         11 . The method of  claim 10 , wherein vector expressing one or more peptides are administered and the peptides comprise one or more epitopes of ETBF and/or  E. coli.    
     
     
         12 . The method of  claim 2 , wherein the administered one or more agents are cytotoxic for ETBF and/or  E. coli.    
     
     
         13 . The method of  claim 2 , wherein the administered one or more agents inhibit bacterial adherence to the subject's gastrointestinal tract. 
     
     
         14 . The method of  claim 2 , wherein the administered one or more agents comprise an anti-cytokine agent that inhibits IL-17 induction by ETBF bacteria. 
     
     
         15 . The method of  claim 2 , wherein the administered a probiotic agent comprises one or more species of selected from the group consisting of  Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Sutterella, Bilophila, Campylobacter, Wolinella, Butyrovibrio, Megamonas, Desulfomonas, Desulfovibrio, Bifidobacterium, Lactobacillus, Eubacterium, Actinomyces, Eggerthella, Coriobacterium, Propionibacterium , non-spore-forming anaerobic gram-positive bacilli,  Bacillus, Peptostreptococcus Peptococcus, Acidaminococcus, Ruminococcus, Megasphaera, Gaffkya, Coprococcus, Veillonella, Sarcina, Clostridium, Aerococcus, Streptococcus, Enterococcus, Pediococcus, Micrococcus, Staphylococcus, Corynebacterium , Enterobacteriaceae, Pseudomonadaceae or combinations thereof. 
     
     
         16 . The method of  claim 1 , further comprising administering to the subject a chemotherapeutic agent. 
     
     
         17 . The method of  claim 1 , wherein the cancer is colorectal cancer (CRC). 
     
     
         18 . A composition comprising a therapeutically effective amount of one or more antibacterial agents and/or one or more probiotics, wherein the antibacterial agents are bactericidal and/or bacteriostatic for enterotoxigenic  Bacteroides fragilis  (ETBF) and  Escherichia coli  ( E. coli ). 
     
     
         19 . The composition of  claim 18 , further comprising one or more probiotics and/or chemotherapeutic agents. 
     
     
         20 . A method of preventing colorectal cancer or treating a subject for colorectal cancer, comprising administering to the subject an antimicrobial agent and/or probiotic, wherein colibactin (clbB) and  Bacteroides fragilis  toxin (bft) are detected in mucosa of a subject's gastrointestinal tract; or
 A method of treating a neoplastic condition in a subject comprising:   detecting a bacterial biofilm within the gastrointestinal tract of a subject and administering an antimicrobial agent or a probiotic agent to the subject in an amount effective to reduce the size of the bacterial biofilm; thereby,   treating or preventing a neoplastic condition in the subject; or   A method of treating colorectal cancer, comprising administering a chemotherapeutic agent and a pharmaceutical composition comprising a therapeutically effective amount of an antimicrobial agent to a subject in need thereof, wherein the antimicrobial agents comprise one or more bactericidal and/or bacteriostatic agents for enterotoxigenic  Bacteroides fragilis  (ETBF) and/or  Escherichia coli  ( E. coli ); or   A method of treating colorectal cancer, comprising administering a one or more immune modulating agents and a pharmaceutical composition comprising a therapeutically effective amount of an antimicrobial agent to a subject in need thereof, wherein the antimicrobial agents comprise one or more bactericidal and/or bacteriostatic agents for enterotoxigenic  Bacteroides fragilis  (ETBF) and/or  Escherichia coli  ( E. coli ).   
     
     
         21 - 27 . (canceled) 
     
     
         28 . A kit for detecting enterotoxigenic  Bacteroides fragilis  (ETBF) and  Escherichia coli  ( E. coli ) comprising:
 a synthetic oligonucleotide conjugated to a detectable label, wherein the synthetic oligonucleotide specifically hybridizes to  Bacteroides fragilis  or  Bacteroides fragilis  toxin (bft); and,   a synthetic oligonucleotide conjugated to a detectable label, wherein the synthetic oligonucleotide specifically hybridizes to  Escherichia coli  or colibactin (clbB);
 or, 
   one or more antibodies specific for one or more epitopes of ETBF and/or  E. coli.      
     
     
         29 - 40 . (canceled)