Defining the genetic requirements for MABS and MABR colony morphotypes of Mycobacteroides abscessus
Author(s)
Patel, Evani N.
Advisor(s)
Editor(s)
Collections
Supplementary to:
Permanent Link
Abstract
Mycobacteroides abscessus is a rapidly growing, multi-drug tolerant bacterium, that is becoming more important in the infectious disease field due to its detrimental respiratory infections. This is a significant problem particularly for persons with Cystic Fibrosis because their genetic mutation leads to mucus buildup in their lungs, providing an ideal living environment for M. abscessus to establish an infection. M. abscessus can present as either a smooth or rough colony morphology, the latter of which causes more pathology in human lungs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and nitric oxide (NO) have been used in MAB treatment; however, it is unclear if the treatment will be effective against both morphotypes. Because the rough morphotype elicits a proinflammatory response by the host, including increased NO production, it is hypothesized that the rough morphotype is better equipped to survive NO treatment. To address this question, the survival of both morphotypes following NO treatment was quantified using transposon insertion sequencing. To confirm the findings, CRISPR-interference was utilized to conditionally knockdown 3 genes required for survival: MAB_0428 and MAB_1959 for MABS and MAB_0519 for MABR. MAB_0428 and MAB_1959 were confirmed to be required for only MABS survival and MAB_0519 was confirmed to be required only in MABR survival. These findings will inform the field of differences between MAB morphotypes physiologies when treated with NO which should be considered in future treatment.
Sponsor
Date
Extent
Resource Type
Text
Resource Subtype
Undergraduate Research Option Thesis