Evolution & adaptation in pathogenicity
“Nothing in biology makes sense except in the light of evolution” (T.Dobzhansky)
The host-pathogen interaction is no exception from this rule: while the pathogens adapt to the specific stresses and requirements inside their hosts, the hosts themselves are selected for best defense against damage done by these microorganisms. This evolutionary battle led to many astonishingly specific adaptations, from optimized nutrient uptake systems to our adaptive immunity.
We are interested in the mechanisms responsible for the adaptation of Candida albicans and C. glabrata, the two most important opportunistic pathogens among the Candida species, during the infection process. It is known for both species that they exhibit phenotypic and genotypic plasticity and can therefore react to changing environments by generating new phenotypes. For example, microevolution has clearly been demonstrated for the acquisition of high levels of antifungal drug resistance. In our laboratory, we used serial passage experiments to monitor the in vitro adaptation of fungi to macrophages, the “big eaters” of the immune system. We used two models: a wild type strain of C. glabrata and a hyphal-deficient C. albicans strain, which cannot escape from macrophages (as C. albicans normally does). In both cases we observed a striking change in the morphology of the strains after a series of co-culture passages. Usually, both strains grow as single cells, but during the microevolution experiment this growth form switched to a more filamentous form. Interestingly, the ability to form filaments is a well characterized virulence trait in wild type C. albicans, which was recreated here. We characterized the evolved strains in more detail using in vitro and in vivo experiments to investigate the impact of this phenotypic alteration on the pathogenicity of the strains. To determine the underlying genetic mechanisms, which cause the phenotypic alterations, we used different molecular techniques like microarrays, DNA and RNA sequencing. An in vivo adaptation experiment of C. albicans to the specific environment in the kidney complements our investigations into the adaptability of pathogenic yeasts in the host.


(2021) Experimental evolution of Candida by serial passaging in host cells. Methods Mol Biol 2260, 145-154. Details PubMed
(2020) Wettrüsten zwischen Pilz und Wirt. BIOSpektrum 26(3), 280-286. Details PubMed PDF
(2020) Candidalysin is a potent trigger of alarmin and antimicrobial peptide release in epithelial cells. Cells 9(3), 699. Details PubMed Open Access PDF
(2020) Fungal factors involved in host immune evasion, modulation and exploitation during infection. Cell Microbiol 23(1), e13272. Details PubMed Open Access PDF
(2020) Ahr1 and Tup1 contribute to the transcriptional control of virulence-associated genes in Candida albicans. mBio 11(2), e00206-20. Details PubMed Open Access PDF
(2020) Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome 8(1), 133. Details PubMed Open Access PDF
(2020) A TRP1-marker-based system for gene complementation, overexpression, reporter gene expression, and gene modification in Candida glabrata. FEMS Yeast Res 20(8), foaa066. Details PubMed Open Access
(2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev 43(5), 517-547. Details PubMed Open Access
(2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176(6), 1340-1355. Details PubMed Open Access PDF
(2019) The Candida albicans exotoxin Candidalysin promotes alcohol-associated liver disease. J Hepatol 72(3), 391-400. Details PubMed
(2019) Cooperative role of MAPK pathways in the interaction of Candida albicans with the host Epithelium. Microorganisms 8(1), 48. Details PubMed Open Access PDF
(2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother 63(9), e00707-19. Details PubMed Open Access PDF
(2019) ZNF518B gene up-regulation promotes dissemination of tumour cells and is governed by epigenetic mechanisms in colorectal cancer. Sci Rep 9(1), 9339. Details PubMed Open Access PDF
(2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297. Details PubMed Open Access PDF
(2019) Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci 29(2), 480-493. Details PubMed
(2019) RNAi as a tool to study virulence in the pathogenic yeast Candida glabrata. Front Microbiol 10, 1679. Details PubMed Open Access PDF
(2019) Candidalysin: Discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. Details PubMed Open Access PDF
(2019) Host-pathogen interactions during female genital tract infections. Trends Microbiol 27(12), 982-996. (Review) Details PubMed
(2019) Antivirulence and avirulence genes in human pathogenic fungi. Virulence 10(1), 935-947. Details PubMed Open Access PDF
(2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488. Details PubMed Open Access PDF
(2018) Metals in fungal virulence. FEMS Microbiol Rev 42(1), fux050. (Review) Details PubMed Open Access
(2018) Power spectrum consistency among systems and transducers. Ultrasound Med Biol 44(11), 2358-2370. Details PubMed Open Access
(2018) Two's company: studying interspecies relationships with dual RNA-seq. Curr Opin Microbiol 42, 7-12. (Review) Details PubMed Open Access PDF
(2017) Encapsulation of antifungals in micelles protects Candida albicans during gall-bladder infection. Front Microbiol 8, 117. Details PubMed Open Access
(2016) Candida species rewired hyphae developmental programs for chlamydospore formation. Front Microbiol 7, 1697. Details PubMed Open Access
(2016) Widespread inter- and intra-Ddmain horizontal gene transfer of d-amino acid metabolism enzymes in eukaryotes. Front Microbiol 7, 2001. Details PubMed Open Access
(2015) Csr1/Zap1 maintains zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 14(7), 661-670. Details PubMed Open Access PDF
(2015) Of mice, flies - and men? Comparing fungal infection models for large-scale screening efforts. Dis Model Mech (8), 473-486. Details PubMed Open Access PDF
(2014) Adaptive prediction as a strategy in microbial infections. PLOS Pathog 10(10), e1004356. Details PubMed Open Access
(2014) One small step for a yeast - Microevolution within macrophages renders Candida glabrata hypervirulent due to a single point mutation. PLOS Pathog 10(10), e1004478. Details PubMed Open Access
(2014) Fine-scale chromosomal changes in fungal fitness. J Curr Fungal Infect Rep Vol. 8(2), 171-178. (Review) Details
(2014) Gene expansion shapes genome architecture in the human pathogen Lichtheimia corymbifera: an evolutionary genomics analysis in the ancient terrestrial Mucorales (Mucoromycotina). PLOS Genetics 10(8), e1004496. Details PubMed Open Access
(2014) Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant. PLOS Genet 10(12), e1004824. Details PubMed Open Access
(2013) Two unlike cousins: Candida albicans and C. glabrata infection strategies. Cell Microbiol 15(5), 701-708. (Review) Details PubMed Open Access
(2013) Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney. PLOS One 8(5), e64482. Details PubMed Open Access