Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized that blocking the recovery from the condensed state could weaken the bacteria. We showed that after inducing DNA condensation, and subsequent blocking of acetylation of DNA binding proteins, the DNA localization in the bacteria is altered. Importantly under these conditions, Mycobacterium smegmatis did not replicate and its survival was significantly reduced. Our work demonstrates that agents that block recovery from the condensed state of the nucleoid can be exploited as antibiotic. The combination of fusidic acid and inhibition of acetylation of DNA binding proteins, via the Eis enzyme, potentiate the efficacy of fusidic acid by 10 and the Eis inhibitor to 1,000-fold. Hence, we propose that successive treatment with antibiotics and drugs interfering with recovery from DNA condensation constitutes a novel approach for treatment of tuberculosis and related bacterial infections.

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This study was conducted on clinical cases of broiler chicken brought at National Avian Disease Investigation Laboratory (NADIL) and Veterinary Teaching Hospital, Agriculture and Forestry University during the period of December, 2018 to April, 2019. The study was aimed to find the antibiogram pattern of Escherichia coli, Salmonella species and Staphylococcus species. A total of 50 ill broiler liver samples were collected and inoculated in Nutrient Agar, XLD agar Mac-Conkey agar, EMB Agar and Mannitol Salt Agar and incubated for 24 hours at 370C. During microbiological examination, prevalence of E.coli was 36 %, Salmonella species was 2% and Staphylococcus species was 8% where as mixed infection was 40%. Antibiogram profile for E. coli isolates were sensitive to Amikacin (88.89%) followed by Colistin (66.67%), Ciprofloxacin (50%), Levofloxacin (42.10%) and Gentamycin (27.78%) while Ceftriaxone (11.11%) and Tetracycline (11.11%) was recorded as least sensitive, for Salmonella species isolates were highly sensitive to Amikacin (100%) and other remaining antibiotics; Ceftriaxone , Gentamicin, Levofloxacin, Ciprofloxacin, Colistin and Tetracycline were observed to be resistant and for Staphylococcus spp. isolates were sensitive to Amikacin (75%) followed by Gentamicin (25%) , Levofloxacin (25%), and Ciprofloxacin (25%) while Tetracycline and Colistin were resistant. In the conclusion, it is strongly recommended to decrease the unethical use of antibiotics to minimize the development of resistance strain of microbes in the future.