Methods and Compositions for Treatment of Chlamydial Infection and Related Diseases and Disorders

Abstract

The present invention provides compositions and methods of use in the treatment/prevention of chlamydial infection and/or diseases and disorders associated with chlamydial infection in a subject.

What is claimed is: 
     
         1 . A method of treating chlamydial infection and/or treating and/or preventing a disease or disorder caused by or associated with chlamydial infection in a subject, comprising administering to the subject an effective amount of an inhibitor of epidermal growth factor receptor (EGFR) expression and/or activity. 
     
     
         2 . The method of  claim 1 , wherein the inhibitor of EGFR expression and/or activity is an antibody, a tyrosine kinase based inhibitor, an antisense oligonucleotide based inhibitor, FR18, an antibody or small molecule that targets the F-actin binding domain of EGFR, an antibody that targets an EGFR- Chlamydia  interaction, or any combination thereof. 
     
     
         3 . The method of  claim 2 , wherein the antibody is selected from the group consisting of Cetuximab, Panitumumab, Nimotuzumab, Matuzumab, Zalutumab, MDX-447, mAb-806 and any combination thereof. 
     
     
         4 . The method of  claim 2 , wherein the tyrosine kinase based inhibitor is selected from the group consisting of Erlotinib, Gefitinib, Lapatinib, Canertinib, Vandetanib and any combination thereof. 
     
     
         5 . The method of  claim 2 , wherein the antisense oligonucleotide based inhibitor is GEM231. 
     
     
         6 . The method of  claim 1 , wherein the disease or disorder caused by or associated with chlamydial infection is cancer, infertility, osteoporosis, arthritis, Alzheimer's disease, pelvic inflammatory disease, asthma, atherosclerosis, chronic fatigue syndrome, chronic obstructive pulmonary disease, coronary heart disease, metabolic syndrome, multiple sclerosis, myocardial infarction, stroke, Tourette syndrome, and any combination thereof. 
     
     
         7 . The method of  claim 6 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, cervical cancer, head and neck cancer, ovarian cancer and any combination thereof. 
     
     
         8 . The method of  claim 1 , further comprising administering to the subject an antibiotic, a chemotherapeutic agent, an anti-inflammatory agent, an immunomodulatory agent and/or radiation, in any combination. 
     
     
         9 . A method of delivering an agent of interest to a cell that expresses EGFR, comprising contacting the cell with a genetically modified  Chlamydia  organism comprising the agent of interest under conditions whereby the  Chlamydia  organism binds the EGFR on the cell, thereby delivering the agent of interest to the cell. 
     
     
         10 . The method of  claim 9 , wherein the agent of interest is a nucleic acid molecule, a protein, a drug, a small molecule, an imaging agent, a therapeutic agent and any combination thereof. 
     
     
         11 . A method of identifying a substance that inhibits the binding of EGFR to F-actin, comprising:
 a) contacting the substance with EGFR and F-actin under conditions whereby binding of EGFR and F-actin can occur; and   b) assaying for the formation of an EGFR/F-actin binding complex, wherein the absence of formation of an EGFR/F-actin binding complex identifies the substance as a substance that inhibits the binding of EGFR to F-actin.   
     
     
         12 . A method of identifying a subject as having an infection caused by  Chlamydia  or as having had an infection caused by  Chlamydia , comprising:
 a) obtaining a biological sample from the subject; and   b) assaying the sample of (a) for one or more proteins that are altered due to  Chlamydia  infection in the subject; wherein altered is defined as a decrease or increase in the amount of the protein(s), and/or as a decrease or increase or change in the posttranslational modification of the protein(s) and/or as a decrease or increase in activity of the protein(s), and wherein detection of an alteration in the protein(s) relative to a control identifies the subject as having an infection caused by  Chlamydia  or as having had an infection caused by  Chlamydia.     
     
     
         13 . A method of identifying a subject as having an increased likelihood of having or developing a disease or disorder associated with infection caused by  Chlamydia , comprising:
 a) obtaining a biological sample from the subject; and   b) assaying the sample of (a) for one or more proteins that are altered due to  Chlamydia  infection in the subject; wherein altered is defined as a decrease or increase in the amount of the protein(s), and/or as a decrease or increase or change in posttranslational modification of the protein(s) and/or as a decrease or increase in its activity of the protein(s), and wherein detection of an alteration in the protein(s) relative to a control identifies the subject as having an increased likelihood of having or developing a disorder associated with infection caused by  Chlamydia.     
     
     
         14 . A method of identifying a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated, comprising:
 a) obtaining a biological sample from the subject; and   b) assaying the sample of (a) for one or more proteins that are altered due to  Chlamydia  infection in the subject; wherein altered is defined as a decrease or increase in the amount of the protein(s), and/or as a decrease or increase or change in posttranslational modification of the protein(s) and/or as a decrease or increase in activity of the protein(s), and wherein detection of an alteration in the protein(s) relative to a control identifies the subject as a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated.   
     
     
         15 . The method of  claim 14 , further comprising:
 c) providing prophylactic treatment to the subject if the subject is identified in step (b) as a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated; and   d) not providing prophylactic treatment to the subject if the subject is not identified in step (b) as a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated.   
     
     
         16 . A method of guiding a treatment regimen for a subject being treated for a disease or disorder associated with infection caused by  Chlamydia , comprising:
 a) obtaining a first biological sample from the subject prior to or during treatment;   b) assaying the first biological sample for one or more proteins that are altered due to  Chlamydia  infection in the subject, wherein altered is defined as a decrease or increase in the amount of the protein(s), and/or as a decrease or increase or change in posttranslational modification of the protein(s) and/or as a decrease or increase in activity of the protein(s);   c) obtaining a second biological sample from the subject at a subsequent time point during treatment and/or after treatment;   d) assaying the second biological sample for the same one or more proteins that are altered due to  Chlamydia  infection in the subject; and   e) comparing the altered protein(s) assayed in (b) with the same altered protein(s) assayed in (d),   
       wherein a decrease in the amount of altered protein(s) measured in the second biological sample as compared with the amount of altered protein(s) measured in the first biological sample indicates that the treatment regimen is imparting a positive or beneficial effect and should be continued and/or increased and an increase or no change in the amount of altered protein(s) measured in the second biological sample as compared with the amount of altered protein(s) measured in the first biological sample indicates that the treatment regimen is not imparting a positive or beneficial effect and should be discontinued or reduced. 
     
     
         17 . The method of  claim 12 , wherein the protein is selected from the group consisting of EGFR, AKT, STAT3/5, PLCgamma, MKK4, ATR, cyclin B1, GADD45, MDM1, actin, p53, SIRT1-6, alpha-fetoprotein, apolipoprotein A-1, early growth response 1, peroxiredoxin 3, MK167 antigen identified by monoclonal antibody KI67, YWHAE, RbL1, heat shock protein 70 kDa (HSPA8), mitochondrial superoxide dismutase 2, endothelial nitric oxide synthase 3 and any combination thereof. 
     
     
         18 . A method of identifying a subject as having an infection caused by  Chlamydia  or as having had an infection caused by  Chlamydia , comprising:
 a) obtaining a biological sample from the subject; and   b) detecting in the sample of step (a) methylation at specific DNA CpG sites that are altered due to  Chlamydia  infection in the subject; wherein altered is defined as a decrease or increase in the amount of methylation relative to a control, and wherein detection of alteration of methylation at specific DNA CpG sites relative to control identifies the subject as having an infection caused by  Chlamydia  or as having had an infection caused by  Chlamydia.      
     
     
         19 . A method of identifying a subject as having an increased likelihood of having or developing a disease or disorder associated with infection caused by  Chlamydia , comprising:
 a) obtaining a biological sample from the subject; and   b) detecting in the sample of step (a) methylation at specific DNA CpG sites that are altered due to  Chlamydia  infection in the subject, wherein altered is defined as a decrease or increase in the amount of methylation relative to a control, and wherein detection of alteration of methylation at specific DNA CpG sites relative to control identifies the subject as having an increased likelihood of having or developing a disorder associated with infection caused by  Chlamydia.     
     
     
         20 . A method of identifying a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated, comprising:
 a) obtaining a biological sample from the subject; and   b) detecting in the sample of step (a) methylation at specific DNA CpG sites that are altered due to  Chlamydia  infection in the subject, wherein altered is defined as a decrease or increase in the amount of methylation relative to a control and wherein detection of alteration of methylation at specific DNA CpG sites relative to control identifies the subject as a subject for whom prophylactic treatment for a developing a disorder associated with infection caused by  Chlamydia  is indicated.   
     
     
         21 . The method of  claim 20 , further comprising:
 c) providing prophylactic treatment to the subject if the subject is identified in step (b) as a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated; and   d) not providing prophylactic treatment to the subject if the subject is not identified in step (b) as a subject for whom prophylactic treatment for a disease or disorder associated with infection caused by  Chlamydia  is indicated.   
     
     
         22 . A method of guiding a treatment regimen for a subject being treated for a disease or disorder associated with infection caused by  Chlamydia , comprising:
 a) obtaining a first biological sample from the subject prior to or during treatment;   b) detecting in the first biological sample the amount of methylation at specific DNA CpG sites that are altered due to  Chlamydia  infection in the subject;   c) obtaining a second biological sample from the subject at a subsequent time point during treatment and/or after treatment;   d) detecting in the second biological sample the amount of methylation at the same specific DNA CpG sites that are altered due to  Chlamydia  infection in the subject; and   e) comparing the amount of altered methylation as assayed in (b) with the amount of altered methylation at the same sites measured in (d),   
       wherein a decrease in the amount of altered methylation sites measured in the second biological sample as compared with the amount of altered methylation sites measured in the first biological sample indicates that the treatment regimen is imparting a positive or beneficial effect and should be continued and/or increased and an increase or no change in the amount of altered methylation sites measured in the second biological sample as compared with the amount of altered methylation sites measured in the first biological sample indicates that the treatment regimen is not imparting a positive or beneficial effect and should be discontinued or reduced. 
     
     
         23 . The method of  claim 13 , wherein the disease or disorder associated with infection caused by  Chlamydia  is cancer or a precancerous condition.