Browsing by Author "Carilo, I."
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Item Characterization of Two New Multidrug-Resistant Strains of Mycobacterium smegmatis: Tools for Routine In Vitro Screening of Novel Anti-Mycobacterial Agents(Antibiotics, 2019-01) Arthur, P.K.; Amarh, V.; Cramer, P.; Arkaifie, G.B.; Blessie, E.J.S.; Fuseini, M.S.; Carilo, I.; Yeboah, R.; Asare, L.; Robertson, B.D.Mycobacterium tuberculosis is a pathogen of global public health concern. This threat is exacerbated by the emergence of multidrug-resistant and extremely-drug-resistant strains of the pathogen. We have obtained two distinct clones of multidrug-resistant Mycobacterium smegmatis after gradual exposure of Mycobacterium smegmatis mc² 155 to increasing concentrations of erythromycin. The resulting resistant strains of Mycobacterium smegmatis exhibited robust viability in the presence of high concentrations of erythromycin and were found to be resistant to a wide range of other antimicrobials. They also displayed a unique growth phenotype in comparison to the parental drug-susceptible Mycobacterium smegmatis mc² 155, and a distinct colony morphology in the presence of cholesterol. We propose that these two multidrug-resistant clones of Mycobacterium smegmatis could be used as model organisms at the inceptive phase of routine in vitro screening of novel antimicrobial agents targeted against multidrug-resistant Mycobacterial tuberculosis.Item Investigations Into The Mechanisms of Anti-Mycobacterial Drug Resistance Using Antipsychotic Compounds(University of Ghana, 2018-07) Carilo, I.The continual emergence of drug resistant strains of Mycobacterium tuberculosis has caused global public health concerns. This project establishes basis for deciphering diverse resistance mechanisms in mycobacteria which would lead to the development of novel therapeutic options. Unique classes of antipsychotic compounds have been found to possess antifungal and anti mycobacterial activities. The study sought to use antipsychotic compounds and a panel of phenotype modifying compounds to probe for resistance mechanisms in Mycobacterium smegmatis. Pairwise drug combinations (480 drug-pair conditions) between antipsychotic compounds/phenotypic compounds and antimicrobial agents produced resistance breaking interactions (37%) and resistance inducing interactions (6%) in M. smegmatis. The membrane disrupting antipsychotic compound, thioridazine, generated resistance breaking effects with a number of antibiotics with different antimicrobial profiles suggesting cell envelope homeostasis as a possible mechanism of antimicrobial tolerance and resistance. The DNA damaging agent 4 nitroquinoline oxide produced resistance breaking effects in pairwise combinations with 20 antibiotics tested in the study and disrupted biofilm in M. smegmatis, hence supporting the evidence that DNA damage repair is a possible mechanism of antibiotic tolerance. Deferoxamine and sulfometuron which induced biofilm formation in M. smegmatis also promoted mycobacterial resistance to a number of antibiotics. All antipsychotics tested promoted ethidium bromide uptake and reduced the rate of extrusion of ethidium bromide in M. smegmatis and erythromycin-resistant M .smegmatis A. DNA damaging agents inhibited biofilm formation in M. smegmatis and multidrug resistant erythromycin resistant M. smegmatis A, suggesting DNA disruption as a biofilm breaking strategy. The study highlights the usefulness of unrelated drugs and natural products in TB drug discovery while unveiling other determinants of drug resistance.