טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentYelin Idan
SubjectMicrobial Evolution in Real-Time: Identification of
Selective Agents and of Evolvability
Determinants
DepartmentDepartment of Biology
Supervisors Professor Roy Kishony
Professor Oded Beja
Full Thesis textFull thesis text - English Version


Abstract

Bacteria are intimate companions of ours, they constantly occupy our skin and our gut. In these environments, bacteria encounter our immune system, as well as other bacteria, various microorganisms and bacteriophages. Some of these bacteria may invade our bodies, causing infection and eliciting an immune response, as well as a pharmaceutical response represented by antibiotic drugs, all directed to impede bacterial invasion. These environments eventually select for bacteria more adapted to the human host or to antibiotic drugs. Here, we apply an approach of observing evolution in action to study the details of the evolutionary process which human-inhabiting bacteria and bacteria exposed to antibiotics undergo. Using recent advances in DNA sequencing technologies which allow comprehensive characterization of the bacterial genome, we study changes in the genomes of longitudinal clinical isolates of the opportunistic pathogenic bacterium Staphylococcus aureus, and of in vitro evolved bacterial populations of antibiotic resistant Escherichia coli. Regarding the clinical isolates we ask what are the selective pressures shaping their evolution, and in the case of bacteria evolved in vitro to adapt to an antibiotic drug we characterize changes in the rate of evolution as bacteria continuously adapt to increasing drug concentrations. In both cases we analyze the genomes of both ancestor and progeny, and perform experiments in the lab to test our hypotheses stemming from genotypic observations. Focusing on within-host evolution of S. aureus we find unexpectedly that much of the genomic changes do not represent adaptation to factors from the human host environment but rather adapting to a prophage, a bacteria infecting virus which is harbored in the genome of these bacteria. Specifically, we identify a prophage replacement event which advances bacteria carrying it as they inhibit and possibly kill their next of kin while spreading through the colonizing bacterial population. With regard to adaptation of E. coli to an antibiotic drug we characterize an increase in the rate of adaptation to the antibiotic, and identify multiple independent cases of  emergence of similar genomic structures underlying this highly directional facilitation of adaptation to an antibiotic drug. These results expand our understanding of genomic changes underlying adaptive evolutionary processes in bacteria, and may pave new ways for diagnostic and preventive measures taken in our efforts to disrupt these processes.