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.
(2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev 43(5), 517-547.
(2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176(6), 1340-1355.e15.
(2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab [Accepted]
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570.
(2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother 63(9), pii: e00707-19.
(2019) ZNF518B gene up-regulation promotes dissemination of tumour cells and is governed by epigenetic mechanisms in colorectal cancer. Sci Rep 9(1), 9339.
(2019) Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol [Accepted]
(2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297.
(2019) Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci ,
(2019) RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata. Front Microbiol 10, 1679.
(2019) A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans. J Infect Dis [Accepted]
(2019) A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Sci Transl Med [Accepted]
(2019) Candidalysin: discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109.
(2019) Host-Pathogen Interactions during Female Genital Tract Infections. Trends Microbiol , pii: S0966-842X(19)30190-8. (Review)
(2019) Antivirulence and avirulence genes in human pathogenic fungi. Virulence 10(1), 935-947.
(2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488.
(2018) Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis [Accepted]
(2018) Metals in fungal virulence. FEMS Microbiol Rev 42(1), (Review)
(2018) Power Spectrum Consistency among Systems and Transducers. Ultrasound Med Biol [Accepted]
(2018) Two's company: studying interspecies relationships with dual RNA-seq. Curr Opin Microbiol 42, 7-12. (Review)
(2017) Encapsulation of antifungals in micelles protects Candida albicans during gall-bladder infection. Front Microbiol 8, 117.
(2016) Candida species rewired hyphae developmental programs for chlamydospore formation. Front Microbiol 7, 1697.
(2016) Widespread inter- and intra-Ddmain horizontal gene transfer of d-amino acid metabolism enzymes in eukaryotes. Front Microbiol 7, 2001.
(2015) Csr1/Zap1 maintains zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 14(7), 661-670.
(2015) Of mice, flies - and men? Comparing fungal infection models for large-scale screening efforts. Dis Model Mech (8), 473-486.
(2014) Adaptive prediction as a strategy in microbial infections. PLOS Pathog 10(10), e1004356.
(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.
(2014) Fine-scale chromosomal changes in fungal fitness. J Curr Fungal Infect Rep Vol. 8(2), 171-178. (Review)
(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.
(2014) Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant. PLOS Genet 10(12), e1004824.
(2013) Two unlike cousins: Candida albicans and C. glabrata infection strategies. Cell Microbiol 15(5), 701-708. (Review)
(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.
Dr. Sascha Brunke
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Sofia Siscar Lewin
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