• Candida albicans quorum-sensing molecule farnesol modulates staphyloxanthin production and activates the thiol-based oxidative-stress response in Staphylococcus aureus

      Vila, Taissa; Ibrahim, Ahmed; Shetty, Amol C.; McCracken, Carrie; Bruno, Vincent; Jabra-Rizk, Mary Ann; Kong, Eric F. (Taylor and Francis Inc., 2019-07-06)
      Microbial species utilize secreted-signaling molecules to coordinate their behavior. Our previous investigations demonstrated a key role for the Candida albicans-secreted quorum-sensing molecule farnesol in modulating Staphylococcus aureus response to antimicrobials in mixed biofilms. In this study, we aimed to provide mechanistic insights into the impact of farnesol on S. aureus within the context of inter-species interactions. To mimic biofilm dynamics, farnesol-sensitized S. aureus cells were generated via sequential farnesol exposure. The sensitized phenotype exhibited dramatic loss of the typical pigment, which we identified as staphyloxanthin, an important virulence factor synthesized by the Crt operon in S. aureus. Additionally, farnesol exposure exerted oxidative-stress as indicated by transcriptional analysis demonstrating alterations in redox-sensors and major virulence regulators. Paradoxically, the activated stress-response conferred S. aureus with enhanced tolerance to H2O2 and phagocytic killing. Since expression of enzymes in the staphyloxanthin biosynthesis pathway was not impacted by farnesol, we generated a theoretical-binding model which indicated that farnesol may block staphyloxanthin biosynthesis via competitive-binding to the CrtM enzyme crucial for staphyloxanthin synthesis, due to high structural similarity to the CrtM substrate. Finally, mixed growth with C. albicans was found to similarly induce S. aureus depigmentation, but not during growth with a farnesol-deficient C. albicans strain. Collectively, the findings demonstrate that a fungal molecule acts as a redox-cycler eliciting a bacterial stress response via activation of the thiol-based redox system under the control of global regulators. Therefore, farnesol-induced transcriptional modulations of key regulatory networks in S. aureus may modulate the pathogenesis of C. albicans-S. aureus co-infections.
    • Comparative Evaluations of the Pathogenesis of Candida auris Phenotypes and Candida albicans Using Clinically Relevant Murine Models of Infections

      Vila, Taissa; Montelongo-Jauregui, Daniel; Ahmed, Hussian; Puthran, Taanya; Sultan, Ahmed S; Jabra-Rizk, Mary Ann (American Society for Microbiology, 2020-08-05)
      The newly emerged Candida species Candida auris is associated with an exponential rise in life-threatening invasive disease in health care facilities worldwide. Unlike other species, C. auris exhibits a high level of transmissibility, multidrug resistance, and persistence in the environment, yet little is known about its pathogenesis largely due to limited data from animal models. Based on in vitro biofilm evaluations and confocal laser scanning microscopy, C. auris phenotypes with different biofilm-forming abilities were identified, indicating potential clinical implications. Using clinically relevant murine models of implanted catheter, oral, and intraperitoneal infections, we comparatively evaluated the host site-specific pathogenic potential of C. auris phenotypes and Candida albicans Based on the results of microbial recovery and scanning electron microscopy analysis of explanted catheters, compared to C. albicans, C. auris more avidly adhered and formed biofilms on catheters. However, although C. auris adhered to oral tissue ex vivo, unlike C. albicans, it failed to colonize the oral cavity in vivo, as demonstrated by microbial recovery and tissue histopathology analysis. In contrast, recovery from peritoneal lavage fluid and kidneys during time course experiments demonstrated that C. auris persisted longer in the peritoneal cavity and kidneys. Although there were clear niche-specific differences in pathogenic features between C. auris and C. albicans, no significant differences were noted between the C. auris phenotypes in vivo The combined findings highlight unique niche-specific pathogenic traits for C. auris warranting further investigations. Understanding the factors contributing to the rise of C. auris as a nosocomial pathogen is critical for controlling the spread of this species.IMPORTANCE The newly emerged Candida species C. auris has been associated with an exponential rise in invasive disease in health care facilities worldwide with a mortality rate approaching 60%. C. auris exhibits a high level of transmissibility, multidrug resistance, and persistence in hospital environments, yet little is known about its pathogenesis largely due to limited data from animal studies. We used clinically relevant murine models of infection to comparatively evaluate the host niche-specific pathogenic potential of C. auris and C. albicans Findings demonstrated that C. auris adheres more avidly, forming robust biofilms on catheters implanted in mice. However, although C. auris adhered to oral tissue ex vivo, it failed to colonize the oral cavity in vivo In contrast, in the intraperitoneal infection model, C. auris persisted longer in the peritoneal cavity and kidneys. Understanding the host-pathogen factors contributing to the rise of C. auris as a nosocomial pathogen is critical for controlling the spread of this species.
    • Convalescent serum therapy for COVID-19: A 19th century remedy for a 21st century disease

      Montelongo-Jauregui, Daniel; Vila, Taissa; Sultan, Ahmed S.; Jabra-Rizk, Mary Ann (Public Library of Science (PLoS), 2020-08-12)
    • Editorial overview of Pearls Microbiome Series: E pluribus unum

      Hogan, Deborah A; Heitman, Joseph; Jabra-Rizk, Mary Ann; Knoll, Laura J; Leong, John M; Silverman, Neal (Public Library of Science, 2021-08-31)
    • The power of saliva: Antimicrobial and beyond.

      Vila, Taissa; Rizk, Alexandra M; Sultan, Ahmed S; Jabra-Rizk, Mary Ann (Public Library of Science, 2019-11-14)
    • Prolonged facial mask wear is a concern for the development of dysbiotic microbiome.

      Brooks, John K; Sultan, Ahmed S; Jabra-Rizk, Mary Ann (Elsevier Inc., 2021-11-27)