The catheterized bladder environment promotes Efg1- and Als1-dependent
            <i>Candida albicans</i>
            infection

Bella, Alyssa Ann La; Andersen, Marissa Jeme; Gervais, Nicholas C; Molina, Jonathan Jesus; Molesan, Alex; Stuckey, Peter V.; Wensing, Lauren; Nobile, Clarissa J.; Shapiro, Rebecca; Santiago-Tirado, Felipe H.; Flores-Mireles, Ana L.

doi:10.1126/sciadv.ade7689

Cited by 6 publications

(1 citation statement)

References 62 publications

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“…More recently, CRISPRa techniques have also been applied in fungal pathogens and other fungal species. In C. albicans, CRISPRa techniques have been successfully applied to drive high levels of expression of genes involved in biofilm formation, antifungal drug resistance, and stress tolerance, and phenotypically validate their role in these processes (39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

Functional genetic characterization of stress tolerance and biofilm formation inNakaseomyces glabratavia a novel CRISPR activation system

Maroc,

Shaker,

Shapiro

2023

Preprint

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The overexpression of genes frequently arises inNakaseomyces(formerlyCandida)glabratavia gain-of-function mutations, gene duplication or aneuploidies, with important consequences on pathogenesis traits and antifungal drug resistance. This highlights the need to develop specific genetic tools to mimic and study genetic amplification in this important fungal pathogen. Here, we report the development, validation, and applications of the first CRISPR activation (CRISPRa) system inN. glabratafor targeted genetic overexpression. Using this system, we demonstrate the ability of CRISPRa to drive high levels of gene expression inN. glabrata, and further assess optimal guide RNA targeting for robust overexpression. We demonstrate the applications of CRISPRa to overexpress genes involved in fungal pathogenesis and drug resistance, and detect corresponding phenotypic alterations in these key traits, including the characterization of novel phenotypes. Finally, we capture strain variation using our CRISPRa system in two commonly usedN. glabratagenetic backgrounds. Together, this tool will expand our capacity for functional genetic overexpression in this pathogen, with numerous possibilities for future applications.

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Section: Introductionmentioning

confidence: 99%

Functional genetic characterization of stress tolerance and biofilm formation inNakaseomyces glabratavia a novel CRISPR activation system

Maroc,

Shaker,

Shapiro

2023

Preprint

Self Cite

View full text Add to dashboard Cite

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Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI

Molina,

Kohler,

Gager

et al. 2024

Nat Commun

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Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

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Fungal mechanisms of intracellular survival: what can we learn from bacterial pathogens?

Stuckey

Santiago-Tirado

2023

Infect Immun

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Fungal infections represent a major, albeit neglected, public health threat with serious medical and economic burdens globally. With unacceptably high mortality rates, invasive fungal pathogens are responsible for millions of deaths each year, with a steadily increasing incidence primarily in immunocompromised individuals. The poor therapeutic options and rise of antifungal drug resistance pose further challenges in controlling these infections. These fungal pathogens have adapted to survive within mammalian hosts and can establish intracellular niches to promote survival within host immune cells. To do that, they have developed diverse methods to circumvent the innate immune system attack. This includes strategies such as altering their morphology, counteracting macrophage antimicrobial action, and metabolic adaptation. This is reminiscent of how bacterial pathogens have adapted to survive within host cells and cause disease. However, relative to the great deal of information available concerning intracellular bacterial pathogenesis, less is known about the mechanisms fungal pathogens employ. Therefore, here we review our current knowledge and recent advances in our understanding of how fungi can evade and persist within host immune cells. This review will focus on the major fungal pathogens, including Cryptococcus neoformans, Candida albicans , and Aspergillus fumigatus , among others. As we discover and understand the strategies used by these fungi, similarities with their bacterial counterparts are becoming apparent, hence we can use the abundant information from bacteria to guide our studies in fungi. By understanding these strategies, new lines of research will open that can improve the treatments of these devastating fungal diseases.

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The catheterized bladder environment promotes Efg1- and Als1-dependent Candida albicans infection

Cited by 6 publications

References 62 publications

Functional genetic characterization of stress tolerance and biofilm formation inNakaseomyces glabratavia a novel CRISPR activation system

Functional genetic characterization of stress tolerance and biofilm formation inNakaseomyces glabratavia a novel CRISPR activation system

Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI

Fungal mechanisms of intracellular survival: what can we learn from bacterial pathogens?

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