Browsing by Author "Sweeney, Mollie I"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    A Cluster of Nontuberculous Mycobacterial Tenosynovitis Following Hurricane Relief Efforts.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-06) Turner, Nicholas A; Sweeney, Mollie I; Xet-Mull, Ana M; Storm, Jeremy; Mithani, Suhail K; Jones, David B; Miles, Jeremy J; Tobin, David M; Stout, Jason E

    Background

    Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections.

    Methods

    We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity.

    Results

    Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures.

    Conclusions

    These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.
  • Thumbnail Image
    ItemOpen Access
    Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection.
    (Cell reports, 2022-12) Brewer, W Jared; Xet-Mull, Ana María; Yu, Anne; Sweeney, Mollie I; Walton, Eric M; Tobin, David M
    During mycobacterial infections, pathogenic mycobacteria manipulate both host immune and stromal cells to establish and maintain a productive infection. In humans, non-human primates, and zebrafish models of infection, pathogenic mycobacteria produce and modify the specialized lipid trehalose 6,6'-dimycolate (TDM) in the bacterial cell envelope to drive host angiogenesis toward the site of forming granulomas, leading to enhanced bacterial growth. Here, we use the zebrafish-Mycobacterium marinum infection model to define the signaling basis of the host angiogenic response. Through intravital imaging and cell-restricted peptide-mediated inhibition, we identify macrophage-specific activation of NFAT signaling as essential to TDM-mediated angiogenesis in vivo. Exposure of cultured human cells to Mycobacterium tuberculosis results in robust induction of VEGFA, which is dependent on a signaling pathway downstream of host TDM detection and culminates in NFATC2 activation. As granuloma-associated angiogenesis is known to serve bacterial-beneficial roles, these findings identify potential host targets to improve tuberculosis disease outcomes.