Origin and adaptation of Fusobacterium nucleatum during colonisation of the human colorectal cancer microenvironment
General Genetics and Functional Genome Biology
Hematology, Oncology
Metabolism, Biochemistry and Genetics of Microorganisms
Final Report Abstract
AD is chronic, inflammatory skin disease and its etiology is comprised of host, environmental, and microbial factors. In particular, AD is characterized by the opportunistic pathogen S. aureus colonizing the inflamed, skin lesions of AD patients. However, S. aureus is not a typical skin commensal and the genetic mechanism facilitating colonization and spread are largely unknown. During my DFG funded postdoc in the Lieberman lab at MIT I investigated the microevolution of S. aureus colonizing the body of 25 AD patients collected during a 9-month longitudinal sampling period. In total, we analyzed over 1,500 S. aureus isolates revealing that new mutations spread rapidly across the patient and replace the preexisting diversity. We identify signatures of adaptive evolution in capD, an essential gene part of the polysaccharide capsule operon. We confirm the inferred adaptive effects of capsule loss during AD colonization using a recently, established mouse model and were further able to confirm our results in a metanalysis of S. aureus from 277 individuals. Our results point into new directions for probiotic therapy of AD using capsular Staphylococcus strains, which, however, has to be established and validated carefully given the known role of capsule as a virulence factor. In future, we are going to address fundamental questions in pathogen evolution combining the expertise in genomics, bioinformatics and microbiology I have collected throughout my career.
