rifampin and Communicable-Diseases--Emerging

Topics: Adjuvants, Immunologic; Adult; Animals; Bacterial Vaccines; Child; Communicable Diseases, Emerging; Disease Models, Animal; Humans; Immunotherapy; Leprostatic Agents; Leprosy; Mycobacterium leprae; Neglected Diseases; Post-Exposure Prophylaxis; Rifampin; Vaccines, Synthetic

The spread of multidrug resistant Mycobacterium tuberculosis is one of the major challenges in tuberculosis control. In Eurasia, the spread of multidrug resistant tuberculosis is driven by the M. tuberculosis Beijing genotype. In this study, we examined whether selective advantages are present in the proteome of Beijing isolates that contribute to the emergence of this genotype. To this end, we compared the proteome of M. tuberculosis Beijing to that of M. tuberculosis H37Rv, both in the presence and absence of the first-line antibiotic rifampicin. During rifampicin exposure, both M. tuberculosis genotypes express proteins belonging to the DosR dormancy regulon, which induces a metabolically hypoactive-, drug tolerant phenotype. However, these markers of rifampicin tolerance were already more abundant in the M. tuberculosis Beijing isolate prior to drug exposure. To determine whether the a priori high abundance of specific proteins contribute to the formation of antibiotic resistance in M. tuberculosis Beijing, we quantified the abundance of 33 selected proteins in 27 clinical isolates from the five most common M. tuberculosis lineages using parallel reaction monitoring. The observed pre-existing high abundance of dormancy proteins in Beijing strains provides an evolutionary advantage that allows these strains to persist for prolonged periods during rifampicin treatment.. M. tuberculosis is the leading cause of death by a bacterial infection worldwide. Treatment-regimen to eradicate this pathogen make use of the first-line antibiotic rifampicin, which is considered to be the cornerstone of modern day anti-tuberculosis treatment. Despite the potency of rifampicin, there is an increasing occurrence of rifampicin resistant mutants in a specific cluster of M. tuberculosis, the Beijing genotype. Using both a data dependent acquisition and a targeted proteomic approach we identified markers of rifampicin tolerance to be high abundant in members of the M. tuberculosis Beijing genotype, already prior drug exposure. The identification of this M. tuberculosis Beijing specific trait will contribute to improved diagnostics and treatment of M. tuberculosis.

Topics: Bacterial Typing Techniques; Biomarkers, Pharmacological; China; Communicable Diseases, Emerging; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Humans; Molecular Diagnostic Techniques; Mycobacterium tuberculosis; Proteomics; Rifampin; Tuberculosis, Multidrug-Resistant

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Communicable Diseases, Emerging; Community-Acquired Infections; Endocarditis, Bacterial; Female; Gastrectomy; Genes, Bacterial; Gentamicins; Humans; Lymphoma, B-Cell, Marginal Zone; Methicillin-Resistant Staphylococcus aureus; Mitral Valve Insufficiency; Multiple Sclerosis; Neoplasms, Second Primary; Ovarian Neoplasms; Postoperative Complications; Rifampin; Staphylococcal Infections; Stomach Neoplasms; Vancomycin

Equine proliferative enteropathy (EPE) is an emerging infectious enteric disease caused by the obligate intracellular gram-negative bacterium Lawsonia intracellularis. EPE was tentatively diagnosed in six weanling foals, aged between 5 and 7 months. Clinical signs included depression, anorexia, ventral oedema, and weight loss. Plasma biochemistry consistently revealed severe hypoproteinaemia. The ante-mortem diagnosis of EPE was based on clinical signs, hypoproteinaemia (6/6), the detection of moderate-to-high titres of L. intracellularis antibody (6/6), and severe thickening of the small intestinal wall on ultrasonography (2/2), or L. intracellularis detected in faeces by PCR (I/2). The first foal died despite treatment and at post-mortem examination the tentative diagnosis was EPE. Three foals from the same farm, which showed similar clinical symptoms were treated with azithromycin and rifampicin; two survived. Post-mortem examination of the foal that died confirmed the tentative clinical diagnosis of EPE on the basis of the lesions found and the detection of L. intracellularis--DNA in the ileum and jejunum. The fifth foal died despite intensive treatment and the post-mortem examination revealed lymphohistiocytic enteritis, typhlitis, and widespread thrombosis in several organs. The sixth foal recovered completely after treatment. This report confirms the presence of clinical L. intracellularis infection in weanling foals in the Netherlands and shows the difficulty in reaching a definitive ante-mortem diagnosis.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Azithromycin; Communicable Diseases, Emerging; Desulfovibrionaceae Infections; Disease Outbreaks; Enteritis; Female; Horse Diseases; Horses; Lawsonia Bacteria; Male; Netherlands; Rifampin; Weaning