Molecular and Virulence Traits of Bacteria & Fungi Causing Persistent Infections

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Abstract

Core and pan genome analyses revealed that Mycobacterium abscessus subspecies massiliense (M. massiliense) outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic (not outbreak-related) isolates. However, pulmonary outbreak isolates were more likely to have antimicrobial resistance mutations compared to sporadic isolates. We characterized serial isolates from two CF patients with chronic pulmonary M. massiliense infection leading to death. One of the patients was the index case of a CF Center mycobacterial outbreak. Comparative genomic analysis revealed mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Interestingly, mutations in 23S rRNA (macrolide resistance), mmpL4 (lipid metabolism), porin locus (transport of hydrophilic solutes) and tetR genes (transcriptional regulation) occurred in isolates from both CF patients. We plan to continue using comparative genomics, susceptibility testing, and virulence studies to shed light on evolution of mycobacteria in the immunocompromised host. Current projects include: 1) Genomic comparison serial M. abscessus isolates with increasing MICs to clarithromycin, amikacin and imipenem. 2) Evolution and diversification of M abscessus in soft tissue infections.