Research

Master's Thesis - SF State University

Phylogenetic Approach to Understand the Evolution of Antibiotic  Resistance in Mycobacterium Tuberculosis

Marisol Fermin Flores & Pleuni Pennings, PhD

Abstract: Mycobacterium tuberculosis (Mtb) is the causal agent for a severe bacterial disease that affects the lungs and causes tuberculosis (TB). Due to the increase of drug resistance in Mtb, treating TB effectively has become harder. It is critical to understand the evolution and spread of drug resistance in TB to find ways to prevent drug-resistant infections. In principle, there are two ways in which a host can get infected with an Mtb strain that is resistant to a given drug: through de novo evolution or via transmission of an already resistant strain. In de novo evolution, the patient is infected with a susceptible strain, which then evolves to become resistant during treatment; alternatively, an already resistant strain is transmitted from another host.  It is not well understood how much resistance is due to transmission. Understanding the importance of transmission for a given drug or country can help guide new policies or interventions to prevent transmission. Our objective is to determine the relative roles of de novo and transmitted resistance using publicly available data and a phylogenetic approach. The plan is to use a previously established approach in the Pennings lab to (1) create a phylogenetic tree from a publicly available genome sequences and (2) to identify phylogenetic clusters of drug resistant strains (using phytools in R) and (3) compare cluster sizes for resistances to different drugs. It is expected that host-to-host transmission of resistant strains leads to clusters of phylogenetically related strains that share drug resistance mutations. Findings from this study will help us understand the relative roles of de novo evolution and transmission for resistance in Mtb. Understanding Mtb drug resistance in tuberculosis can have a significant impact, as we might be able to provide personalized medicine and uncover ways to reduce rates of evolution and transmission of resistant Mtb.

Key words: Antibiotic Resistance (AR), Mycobacterium Tuberculosis (Mtb), Whole Genome Sequence (WGS), Phylogenetic tree, De Novo, Transmission