Biology subjects

Hill, D. J.

Publications and source records attributed to Hill, D. J..

2 recordsLinked to original sources

bioRxiv2020

Mechanisms of interaction of staphylococcus aureus with human mesenchymal stem cells and their differentiated phenotypes

Mesenchymal stem cells (MSCs) are multipotent cells commonly derived from the bone marrow, adipose tissue and placenta. Human bone marrow derived MSCs migrate to a site of injury, release proinflammatory cytokines and modulate T-cell proliferation. At sites of injury, MSCs may well encounter bacterial pathogens most commonly the Gram positive pathogen Staphylococcus aureus. However, the precise molecular mechanism(s) of this interaction remain to be elucidated. In the present study we aim to show if a direct interaction occurs between S. aureus and bone marrow derived MSCs and identify if MSCRAMMs have a role in this interaction. We further aim to compare S. aureus interaction with cells that differentiate from MSCs, namely; osteoblasts, adipocytes and chondrocytes, since MSCs co-exist in the niche of these cells. Our results showed that S. aureus is able to interact with MSCs in the form of adhesion and invasion to the cells, and that this interaction is largely dependent on the expression of fibronecting-binding protein (FnBP) by S. aureus. We also showed that the same mechanism of interaction to osteoblasts, adipocytes and chondrocytes that are directly differentiated from the same MSCs. Finally, we have found that the presence of 10% FBS in the infection medium is essential as it helps in achieving the best specific bacterial-cell association with the least background association. The results reveals a mechanism of interaction between S. aureus and MSCs that could pave the way for therapeutic intervention that minimises the burden of infection in inflammatory diseases.

microbiology↗

bioRxiv2018

Assessment of Environmental and Occupational Exposure while Working with Candida auris a Multidrug Resistant (MDR) Fungus in the Animal Facility.

In less than a decade since its identification in 2009, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality. Unlike any other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models use inoculums as high as 107-108 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. Using real-time quantitative PCR and culture, we monitored the animal holding room as well as the procedure room for up to six months while working with an intravenous model of C. auris infection. This study determined that shedding of the organism is dose-dependent, as detectable levels of C. auris were detected in the cage bedding when mice were infected with 107 and 108 cells, but not with doses of 105 and 106 cells. Autoclaving bedding in closed micro-isolator cages was found to be an effective way to minimize exposure to animal caretakers. We found that tissue necropsies of infected mice were also an important source of potential source exposure to C. auris. To mitigate these potential exposures, we implemented a rigorous \"buddy system\" workflow and a disinfection protocol that uses 10% bleach followed by 70% ethanol and can be used in any animal facility when using small animal models of C. auris infection.

microbiology↗