Molecular and Virulence Traits of Bacteria & Fungi Causing Persistent Infections

Clinical Center

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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. Two specific examples are summarized below: 1) We have previously performed extensive molecular identification and typing of clinical isolates of M. abscessus and the closely related newly-described subspecies M. massiliense and M bolletii from NIH patients. Pan-mycobacterial microarray platforms were used to reveal genomic differences among these clonal groups and led to a rapid and cost effective PCR-based assay for identification and typing of these organisms and detection of the inducible clarithromycin erm (41) gene. More recently, we performed whole genome sequencing of serial isolates and outbreak-linked strains of Mycobacterium massiliense and identified virulence and epidemiological traits associated to multi-nation outbreaks. 2) We have recently described a novel and emerging species of molds causing disease in immunocompromised patients. One example is the isolation of a novel species of Phellinus from a patient with chronic granulomatous disease. Review of clinical charts and laboratory data unveiled additional cases of this species and related species within the genus. Another example is the recovery of a recently described species of Mucor, Mucor velutinosus, from several immunocompromised patients