Associate Professor Mary Ann Jabra-Rizk, PhD

The research in our laboratory focuses on the characterization of virulence factors in the opportunistic fungal pathogen Candida albicans and on analyzing the factors that play a role in the transition between colonization and infection. We have several ongoing projects pursuing different aspects of Candida pathogenesis including biofilm formation, drug resistance and fungal-bacterial interactions in biofilm. Our studies have focused on studying the interactions between C. albicans and the bacterial species Staphylococcus aureus, the most commonly co-isolated human pathogens largely due to their ability to adhere to biotic and abiotic surfaces. Biofilm-related polymicrobial infections are typically associated with the presence of catheters and indwelling medical devices. By taking various approaches, our in vitro and in vivo studies have provided strong evidence indicating a strong affinity between these diverse species impacting biofilm development, drug tolerance and evasion of host immune factors. We are currently studying the clinical and therapeutic implications of their synergistic interaction using a clinically relevant mouse subcutaneous catheter model to study in vivo-grown mixed biofilms. Through dissecting the regulatory and transcriptional pathways uniquely expressed during co-infection, we aim to identify microbial phenotypes of enhanced pathogenic potential central to the persistence and enhanced drug tolerance of biofilm co-infections. The overall goal of this project is to identify novel therapeutic strategies targeting complex polymicrobial infections.

 

We are also investigating the role of host oral innate immunity, specifically the salivary antifungal peptide histatin-5, in protection of the oral cavity against C. albicans colonization. As oral candidiasis is the most prevalent opportunistic infection in HIV+ individuals, we hypothesize that decreased histatin-5 salivary levels play a key role in the enhanced predisposition of this patient population to oral candidiasis. In this project, using prospective clinical studies, we aim to define a novel mechanism behind the prevalence of oral candidiasis in these vulnerable individuals. In light of the increasing emergence of C. albicans strains resistant to the common antifungals, antimicrobial peptides have gained considerable attention as alternate therapeutics and specifically histatin-5. We recently developed the first pharmaceutically viable bioadhesive hydrogel formulation of histatin-5 (under patenting) designed for oral topical application for the prevention and treatment of oral candidiasis. The efficacy of the novel formulation was demonstrated in vivo in our mouse model of oral candidiasis. Currently, we are developing mouse models of periodontal disease and wound healing in order to explore the anti-inflammatory and tissue regeneration properties of the new formulation.

 

Recent studies have reported high prevalence for the cariogenic bacterial species Streptococcus mutans in dental biofilms where C. albicans resides, suggesting that this fungal-bacterial interaction may mediate development of dental caries. Therefore, another ongoing project in our laboratory is to investigate the co-adherence and co-colonization of these species in vitro and in vivo within the context of dental caries development.

 

SELECTED PUBLICATIONS

 

  1. Scheper MA, Shirtliff ME, Meiller TF, Peters B, Jabra-Rizk MA. “Farnesol a fungal quorum sensing molecule triggers apoptosis in human oral squamous carcinoma cells”. Neoplasia 2008; 10(9): 954-963.
  2. Meiller TF, Hube B, Schild L, Shirtliff ME, Scheper MA, Winkler R, Ton A, Jabra-Rizk MA. “Novel immune evasion strategy of Candida albicans: Proteolytic cleavage of a salivary antimicrobial peptide”. PLoS ONE 2009; 4(4): e5039, 1-9. PMID: 19352427A.
  3. Shirtliff ME, Krom BP, Meijering R,Peters BM, Zhu J, Jabra-Rizk MA. “Farnesol-induced apoptosis in Candida albicans”. Antimicrob Agents Chemother 2009; 53(6): 2392-2401.
  4. Peters BM,Zhu J,Fidel PL,Scheper MA, Hackett W, El Shaye S, Jabra-Rizk MA.”Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infection”. FEMS Yeast Res 2010; 10(5): 597-604.
  5. Peters BM, Jabra-Rizk MA, Leid JG, Costerton JW, Shirtliff ME. “Microbial interactions and differential protein expression within Candida albicans-Staphylococcus aureus polymicrobial biofilms”. FEMS Immunol Med Microbiol 2010; (59): 494-503.
  6. Peters BM, Shirtliff ME,Jabra-Rizk MA. “Antimicrobial peptides: Primeval molecules or novel drugs?” PLoS Pathog 2010: 6(10): e1001067.
  7. Jabra-Rizk MA. “Pathogenesis of polymicrobial biofilms”. Open Mycol J 2011; (5)39-43.
  8. Dawson CC, Intapa C,Jabra-Rizk MA. “Persisters”: Survival at the cellular level”.  PLoS Pathog 2011: 7(7): e1002121.
  9. Zhu J, Krom BP, Sanglard D, Intapa C, Dawson CC, Peters BM, Shirtliff ME,Jabra-Rizk MA. “Farnesol-induced apoptosis in Candida albicans is mediated by Cdr1-p extrusion and depletion of intracellular glutathione”. PLoS ONE 2011: 6(12): e28830.
  10. Peters BM, Jabra-Rizk MA, O’May GA, Costerton W, Shirtliff ME. “Polymicrobial interactions in biofilms: Impact on pathogenesis and human disease”. Clin Microbiol Rev 2012: 25(1): 193-213.
  11. Peters BM, Ovchinnikova E, Schlecht LM, Hoyer LL, Busscher HK, van der Mei HC, Krom BP,Jabra-Rizk MA, Shirtliff ME. “Staphylococcus aureus adherenceto Candida albicans hyphae is mediated by the hyphal adhesin Als3p”. Microbiol 2012 (2): 2975-86.
  12. Khan SA, Fidel PL, Al Thunayyan A, Meiller TF, Jabra-Rizk MA. “Impaired histatin-5 level and salivary antimicrobial activity against C. albicans in HIV-infected individuals”. J AIDS Clin Res 2013; 4(2):1-6. 
  13. Metwalli KH, Khan SA, Krom BP, Jabra-Rizk MA. “Streptococcus mutans, Candida albicans and the human mouth: A sticky situation”. PLoS Pathog 2013; 9(10); e1003616.
  14. Demuyser L,Jabra-Rizk MA, Van Dijck P. “Microbial cell surface proteins and secreted metabolites involved in multispecies biofilms”. Pathog Dis 2014; 70, 219–230.
  15. Schlecht LM, Peters BM, Krom BP, Hänsch GM, Filler SG,Jabra-Rizk MA, Shirtliff ME. “Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion in a murine model of oral co-infection”. Microbiol 2014; doi.org/10.1099/mic.0.083485-0.
  16. Intapa C, Basile J, Jabra-Rizk MA. “Farnesol-induced apoptosis in oral squamous carcinoma cells is mediated by MRP1 extrusion and depletion of intracellular glutathione”. Trends in Cancer Res 2014 (10) 1–16.
  17. Kong EF, Kucharíková S, Van Dijck P, Peters BM, Shirtliff ME,Jabra-Rizk MA. “Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease”. Infect Immun 2015; 83(2). 83:000–000. doi:10.1128/IAI.02843-14.
  18. Kong EF,Jabra-Rizk MA. “The Great Escape: Pathogen versus Host”. PLoS Pathog 2015; e1004661.
  19. Khan SA, Kong EF, Meiller TF, Jabra-Rizk MA. "Periodontal Diseases: Bug induced, host promoted." PLoS Pathog 2015; 11(7): e1004952.
  20. Tsui C, Kong EF, Jabra-Rizk MA. "Pathogenesis of Candida albicans biofilm." Pathog Dis 2016; doi:10.1093/femspd/ftw018.

 

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/46012026/

 

 

EDUCATION AND TRAINING:

 

Ph. D Microbiology and Immunology