tetracycline and Tuberculosis

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a major health threat listed among the top 10 causes of death worldwide. Treatment of multidrug-resistant Mtb requires use of additional second-line drugs that prolong the treatment process and result in higher death rates. Our team previously identified a 2-pyridone molecule (C10) that blocks tolerance to the first-line drug isoniazid at C10 concentrations that do not inhibit bacterial growth. Here, we discovered that the genes rv3160c and rv3161c are highly induced by C10, which led us to investigate them as potential targets. We show that Rv3160c acts as a TetR-like transcriptional repressor binding to a palindromic sequence located in the rv3161c promoter. We also demonstrate that C10 interacts with Rv3160c, inhibiting its binding to DNA. We deleted the rv3161c gene, coding for a putative oxygenase, to investigate its role in drug and stress sensitivity as well as C10 activity. This Δrv3161c strain was more tolerant to isoniazid and lysozyme than wild type Mtb. However, this tolerance could still be blocked by C10, suggesting that C10 functions independently of Rv3161c to influence isoniazid and lysozyme sensitivity.

Topics: Antitubercular Agents; Bacterial Proteins; Drug Resistance, Microbial; Gene Expression; Gene Expression Regulation, Bacterial; Isoniazid; Mycobacterium tuberculosis; Oxygenases; Protein Binding; Repressor Proteins; Tetracycline; Transcription Factors; Tuberculosis; Tuberculosis, Multidrug-Resistant

Eleven antimicrobial peptides (AMP) based on the incorporation of cyclic tetra substituted C(α) amino acids, as well as other unnatural amino acids were designed, synthesized and screened for in vitro activity against 18 strains of bacteria as well as 12 cancer cell lines. The AMPs discussed herein are derived from the following peptide sequence: Ac-GF(X)G(X)B(X)G(X)F(X)G(X)GB(X)BBBB-amide, X=any one of the following residues, A5c, A6c, Tic or Oic and B=any one of the following residues, Arg, Lys, Orn, Dpr or Dab. A diversity of in vitro inhibitory activity was observed for these AMPs. Several analogs exhibited single digit μM activity against drug resistant bacteria including; multiple drug resistant Mycobacterium tuberculosis, extremely drug resistant Mycobacterium tuberculosis and MRSA. The physicochemical properties of the basic amino acid residues incorporated into these AMPs seem to play a major role in defining antibacterial activity. Overall hydrophobicity seems to play a limited role in defining antibacterial activity. The ESKAPE pathogens were used to compare the activity of these AMPs to another family of synthetic AMPs incorporating the unnatural amino acids Tic and Oic. In most cases similarly substituted members of both families exhibited similar inhibitory activity against the ESKAPE pathogens. In specific cases differences in activity as high as 15 fold were observed between analogs. In addition four of these AMPs exhibited promising IC50 (<7.5μM) values against 12 different and diverse cancer cell lines. Five other AMPs exhibited promising IC50 (<7.5μM) values against selected cancer cell lines.

Topics: Amino Acid Sequence; Amino Acids; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Bacterial Infections; Cell Line, Tumor; Humans; Models, Molecular; Mycobacterium tuberculosis; Neoplasms; Peptides; Tuberculosis

Topics: Animals; Azathioprine; Cyclophosphamide; Drug Administration Schedule; Guinea Pigs; Immunity, Cellular; Macrophages; Skin; Skin Tests; Tetracycline; Tuberculosis

Topics: Adult; Diagnosis, Differential; Drug Combinations; Epididymitis; Gonorrhea; Hernia; Humans; Infant, Newborn; Infrared Rays; Male; Orchitis; Penicillins; Phenylbutazone; Prognosis; Prostatitis; Spermatic Cord Torsion; Sulfamethoxazole; Testicular Neoplasms; Tetracycline; Trimethoprim; Tuberculosis

Topics: Antiviral Agents; BCG Vaccine; Bronchitis; Humans; Isoniazid; Respiratory Tract Infections; Tetracycline; Tuberculosis; Virus Diseases

Topics: Amides; Aminosalicylic Acids; Antitubercular Agents; Capreomycin; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Isoniazid; Isonicotinic Acids; Kanamycin; Phenylthiourea; Pyrazinamide; Rifampin; Streptomycin; Tetracycline; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Africa; Asia; Brucellosis; Chloramphenicol; Chloroquine; Fever; Humans; Leishmaniasis, Visceral; Liver Abscess, Amebic; Malaria; Metronidazole; Plasmodium falciparum; Tetracycline; Travel; Trypanosomiasis, African; Tuberculosis; Typhoid Fever; United Kingdom

Topics: Anabolic Agents; Anemia, Aplastic; Blood Cell Count; Blood Transfusion; Chloramphenicol; Erythrocytes; Female; Follow-Up Studies; Germany, West; Glucocorticoids; Hemostatics; Hepatitis; Humans; Male; Mumps; Phenylbutazone; Plasma; Sulfonamides; Tetracycline; Time Factors; Tuberculosis

Topics: Adult; Aged; Ascitic Fluid; Bone Neoplasms; Breast Neoplasms; Cardiovascular Diseases; False Negative Reactions; False Positive Reactions; Female; Filtration; Gastrointestinal Neoplasms; Humans; Male; Membranes, Artificial; Methods; Middle Aged; Neoplasms; Ovarian Neoplasms; Pleural Effusion; Prostatic Neoplasms; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Testicular Neoplasms; Tetracycline; Tuberculosis

Topics: Age Factors; Autopsy; Bronchopneumonia; Child; Child, Preschool; Chlorpromazine; Female; Humans; Infant; Infant, Newborn; Kwashiorkor; Male; Measles; Penicillins; Pertussis Vaccine; Phenobarbital; Prognosis; Seizures; Tetracycline; Tuberculosis; Uganda; Vomiting; Whooping Cough

Topics: Animals; Mice; Staphylococcal Infections; Tetracycline; Tuberculosis

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Bronchitis; Drug Resistance; Drug Resistance, Microbial; Erythromycin; Haemophilus influenzae; Humans; Penicillins; Preventive Medicine; Sputum; Streptococcus pneumoniae; Sulfamethoxypyridazine; Tetracycline; Toxicology; Tuberculosis; United Kingdom

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Antitubercular Agents; Child; Cycloserine; Drug Tolerance; Ethionamide; Isoniazid; Oxytetracycline; Pyrazinamide; Streptomycin; Tetracycline; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Child; Chloramphenicol; Erythromycin; Gastroenterology; Humans; Infant; Infant, Newborn; Infections; Meningitis; Pediatrics; Penicillins; Polymyxins; Respiratory Tract Diseases; Streptomycin; Sulfonamides; Tetracycline; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Child; Diagnosis, Differential; Humans; Isoniazid; Lipids; Paraffin; Penicillins; Pneumonia; Pneumonia, Lipid; Prednisolone; Radiography, Thoracic; Tetracycline; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Actinomycosis; Anti-Bacterial Agents; Diagnosis, Differential; Humans; Iodine; Lung Diseases; Lung Diseases, Fungal; Penicillin V; Penicillins; Radiography, Thoracic; Sulfonamides; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Chickenpox; Child; Clinical Enzyme Tests; Cortisone; Dermatomyositis; Drug Hypersensitivity; Drug Therapy; Humans; Isoniazid; Prednisolone; Streptomycin; Tetracycline; Toxicology; Tuberculosis; Tuberculosis, Miliary

Topics: Antitussive Agents; Bronchitis; Humans; Oxadiazoles; Respiratory System; Respiratory Tract Diseases; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bronchial Fistula; Bronchopneumonia; Cross Infection; Empyema; Humans; Influenza, Human; Lung Abscess; Pneumonectomy; Postoperative Complications; Sputum; Staphylococcal Infections; Surgical Wound Infection; Tetracycline; Thoracic Diseases; Thoracoplasty; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antibiotic Prophylaxis; Humans; Injections, Intravenous; Pneumonectomy; Pneumothorax; Pneumothorax, Artificial; Postoperative Care; Pulmonary Surgical Procedures; Pyrrolidines; Rolitetracycline; Tetracycline; Thoracoplasty; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Drug Therapy; Erythromycin; Humans; Lung Diseases; Lung Diseases, Fungal; Penicillins; Pneumonia; Pneumonia, Pneumococcal; Pneumonia, Rickettsial; Pneumonia, Viral; Streptomycin; Tetracycline; Tuberculosis

Topics: Amphotericin B; Cryptococcosis; Encephalitis; Humans; Isoniazid; Meningoencephalitis; Streptomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Chemoprevention; Child; Communicable Disease Control; Humans; Malaria; Penicillins; Preventive Medicine; Rheumatic Fever; Sexually Transmitted Diseases; Streptococcal Infections; Tetracycline; Tuberculosis; Whooping Cough

Topics: Anti-Bacterial Agents; Bacillus; Biomedical Research; Brucellosis; Chloramphenicol; Chlortetracycline; Communicable Diseases; Cycloserine; Diphtheria; Dysentery; Dysentery, Bacillary; Erythromycin; Escherichia coli Infections; Humans; Influenza, Human; Liver Extracts; Methicillin; Penicillins; Pneumonia; Research; Staphylococcal Infections; Streptomycin; Syphilis; Tetracycline; Trachoma; Tuberculosis; USSR

Topics: Adrenocorticotropic Hormone; Aminosalicylic Acid; Aminosalicylic Acids; Chloramphenicol; Drug Therapy; Isoniazid; Prednisolone; Streptomycin; Surgical Procedures, Operative; Synovitis; Tetracycline; Tuberculosis; Tuberculosis, Ocular; Tuberculosis, Osteoarticular; Tuberculosis, Pulmonary; Tuberculosis, Renal

Topics: Anti-Bacterial Agents; Bacillus; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Streptomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Anti-Bacterial Agents; Antitubercular Agents; Cycloserine; Ethionamide; Humans; Oxytetracycline; Protein Synthesis Inhibitors; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Bronchitis; Penicillins; Protein Synthesis Inhibitors; Tetracycline; Tuberculosis

Topics: Anti-Bacterial Agents; Empyema; Humans; Oleandomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Ear; Kanamycin; Protein Synthesis Inhibitors; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Humans; Oleandomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Humans; Oleandomycin; Sputum; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Female; Humans; Tetracycline; Tuberculosis; Tuberculosis, Female Genital

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Protein Synthesis Inhibitors; Tetracycline; Tuberculosis; Tuberculosis, Osteoarticular

Topics: Animals; Characidae; Humans; Pyrimidines; Tetracycline; Tuberculosis

Topics: Administration, Oral; Anti-Bacterial Agents; Bacteria; Humans; Meningitis; Meningitis, Bacterial; Tetracycline; Tuberculosis; Tuberculosis, Meningeal