Structure-function analysis of carbapenem resistance factor A (CrfA) from Mycobacterium tuberculosis
TB has been touted as one of the top 10 leading causes of death in the latest WHO report (2017). Increasing tolerance to both first line and second line TB drugs has led to the emergence of multi-drug resistant (MDR) and extremely drug-resistant (XDR) Mtb strains. At such a time, carbapenems (a class of β-lactams) have been observed to be highly effective, especially in the presence of β-lactamase inhibitors. However, with enough time Mtb will develop resistance to even these drugs. This paper attempts to analyse CrfA, a gene that appears to be single-handedly involved in conferring carbapenem resistance. It is a relatively new protein hence its structure and function are not known. Homology modelling of CrfA has been performed and multiple models have been generated. Also, function of CrfA was also predicted. These models and functions needed to be verified by studying the protein through various assays for which CrfA needs to be expressed and isolated. E.coli system was used to express CrfA here, allowing for isolation and study of the protein in future studies.
Keywords: tuberculosis, β-lactam, carbapenem, drug resistance, CrfA