Molecular and Virulence Traits of Bacteria & Fungi Causing Persistent Infections

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Abstract

Persistent and chronic infections are maintained by a dynamic modulation of microbe - host cell interactions. During this process, microorganisms evolve and adapt to the host by regulating the expression of different genes, in particular those involved in virulence. At the bacterial population level, specific (possibly hypervirulent) clones may predominate at different times in individuals as well as groups of patients. The timely storage of microbial pathogens in the microbiology laboratory together with the availability of clinical data from the patients allows following virulence traits, host adaptation and changing epidemiology of the pathogens. Three examples are summarized below: 1) Work on Mycobacterium abscessus revealed high relatedness between strains involved in global outbreaks in cystic fibrosis patients. Serial isolates from the index case of a CF outbreak iprovided valuable insights on the adaptative changes of M. abscessus towards more virulent and possibly more transmissible populations. Interestingly, M. abscessus adaptation and virulence traits share some striking similarities to those of Mycobacterium tuberculosis. 2) We characterized Mycobacterium bovis BCG isolates from lung and brain from a previously BCG-vaccinated patient with IFNR1 deficiency. We show that both clinical Isolates derived from the BCG-vaccine but displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. 3) In an effort to address multidrug resistance and treatment challenges of chromic respiratory infections, we have evaluated novel antimicrobial approaches including synthetic peptides and nitric oxide.