AUTHOR=Van Dyck Katrien , Viela Felipe , Mathelié-Guinlet Marion , Demuyser Liesbeth , Hauben Esther , Jabra-Rizk Mary Ann , Vande Velde Greetje , Dufrêne Yves F. , Krom Bastiaan P. , Van Dijck Patrick 

TITLE=Adhesion of Staphylococcus aureus to Candida albicans During Co-Infection Promotes Bacterial Dissemination Through the Host Immune Response

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.624839

DOI=10.3389/fcimb.2020.624839

ISSN=2235-2988

ABSTRACT=<p>Interspecies interactions greatly influence the virulence, drug tolerance and ultimately the outcome of polymicrobial biofilm infections. A synergistic interaction is observed between the fungus <italic>Candida albicans</italic> and the bacterium <italic>Staphylococcus aureus</italic>. These species are both normal commensals of most healthy humans and co-exist in several niches of the host. However, under certain circumstances, they can cause hospital-acquired infections with high morbidity and mortality rates. Using a mouse model of oral co-infection, we previously showed that an oral infection with <italic>C. albicans</italic> predisposes to a secondary systemic infection with <italic>S. aureus</italic>. Here, we unraveled this intriguing mechanism of bacterial dissemination. Using static and dynamic adhesion assays in combination with single-cell force spectroscopy, we identified <italic>C. albicans</italic> Als1 and Als3 adhesins as the molecular players involved in the interaction with <italic>S. aureus</italic> and in subsequent bacterial dissemination. Remarkably, we identified the host immune response as a key element required for bacterial dissemination. We found that the level of immunosuppression of the host plays a critical yet paradoxical role in this process. In addition, secretion of candidalysin, the <italic>C. albicans</italic> peptide responsible for immune activation and cell damage, is required for <italic>C. albicans</italic> colonization and subsequent bacterial dissemination. The physical interaction with <italic>C. albicans</italic> enhances bacterial uptake by phagocytic immune cells, thereby enabling an opportunity to disseminate.</p>