Invasive candidiasis is a fungal infection characterized by a high mortality rate. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family receptors play a crucial role in regulating innate responses of both leukocytes and epithelia. Human CEACAM3, CEACAM5 and CEACAM6 receptors recognize Candida albicans and are expressed in transgenic CEABAC10 mice. In a murine C. albicans infection model, CEABAC10 mice exhibited a shortened survival period attributed to an early cytokine storm, an exacerbated acute phase response, and heightened systemic inflammation compared to their wild-type littermates. The livers and kidneys of CEABAC10 mice displayed intensified purulent necrotizing inflammation, accompanied by increased infiltration of neutrophils and macrophages. Our in vivo and in vitro data indicated that the expression of CEACAM6 on monocytes of CEABAC10 mice caused the elevated cytokine levels and the subsequent exacerbation of the acute phase response upon C. albicans infection, resulting in decreased survival.

ABSTRACT The commensal and pathogenic lifestyles of the opportunistic fungal pathogen Candida albicans require complex signaling networks regulated by protein kinases. To investigate the role of C. albicans protein kinases at the intestinal epithelial interface, we screened a comprehensive protein kinase deletion library for the capacity of the mutants to damage intestinal epithelial cells (IEC). Mutants showing altered IEC cytotoxicity relative to the wild type were further analyzed for their growth and morphology, focusing on hyper-damaging strains to identify kinases that rather prevent host cell damage. Deletion of CRK1 caused increased IEC-specific damage, despite slower growth, reduced hyphal length, and reduced adhesion as compared to wild-type cells. While tissue invasion levels and the formation of transcellular tunnels of the crk1 Δ/Δ mutant were increased, the translocation capacity through the IEC barrier was reduced. Transcriptional and metabolic profiling suggested a role for Crk1 in metabolic adaptation to carbon and nitrogen sources, which was validated by showing that high glucose and amino acids are required for crk1 Δ/Δ to cause increased IEC damage. Deletion of CRK1 rendered C. albicans more susceptible to cell wall and membrane stressors, but caused higher resistance to a catalase-specific and histidine biosynthesis inhibitor. This phenotypic pattern of medium- and epithelial cell type-specific cytotoxicity displayed by a C. albicans protein kinase mutant suggests that Crk1 regulates processes linked to carbon and amino acid metabolism that are relevant to interactions with intestinal epithelial cells. IMPORTANCE Microbial signal transduction pathways regulate adaptation to changing environmental conditions and facilitate the success of many microbes during interactions with their hosts. The fungal pathobiont Candida albicans exists as a harmless commensal on mucosal surfaces of most humans but can also cause superficial and invasive infections under certain circumstances. Both lifestyles require complex signaling networks, predominantly regulated by protein kinases. The C. albicans genome was predicted to encode 108 protein kinases, yet nearly 50% remain uncharacterized. We aimed to dissect the role of C. albicans protein kinases during the transition from commensal to pathogen. We showed that multiple protein kinase genes are involved in epithelial cell damage. Particularly, the protein kinase gene Crk1 was of interest because deletion of CRK1 caused increased damage to intestinal epithelial cells under distinct conditions. Our study links Crk1 with regulation of metabolic processes relevant for commensalism and pathogenicity of C. albicans .

Human pathogenic fungi are increasingly recognized as major threats to human health, yet their complex biology and interactions with the host remain poorly understood. This review highlights the role of image-based systems biology in fungal infection research, emphasizing how computational models bridge experimental observations and mechanistic understanding. Recent advances in imaging, quantitative image analysis, and mechanistic modeling have enabled dynamic and precise characterization of fungal infections. Integrative studies in Candida albicans and Aspergillus fumigatus have linked measurable cellular behaviors to infection outcomes, revealing how fungal growth, immune evasion, and host responses jointly determine disease progression. Computational models now reproduce infection dynamics, identify key parameters shaping immune control, and guide therapeutic strategies. Coupling quantitative imaging with computational modeling transforms fungal systems biology from descriptive observation to predictive and mechanistic insights, enabling the rational design of diagnostics and therapeutic strategies.

Abstract Background The Gram-positive human pathogen Streptococcus pneumoniae adapts its metabolism to the environment during colonization and host invasion. Extracellular vesicles (EVs) are produced by S. pneumoniae in the process of infection but the exact interplay between metabolic adaptation and vesicle formation remains elusive. This study investigates the role of environmental cues in modulating pneumococcal EVs biogenesis and function. Results Here, we demonstrate that exposure to normal human serum induced rearrangement of the pneumococcal cell wall and considerably increased Sp-EVs production. Temperature and pH were critical factors for Sp-EVs formation: 37 °C supported optimal EV production, while bacterial exposure to either basic or acidic environments slowed down pneumococcal EV biogenesis and led to a heterogeneous subpopulation profile. Proteomic analysis revealed that Sp-EVs are enriched in carbon metabolism-related proteins, specifically those associated with glycolysis (e.g. Eno, GapA, GapN, GpmA, PfkA, PykF, and Tpi). Moderate glucose availability enhanced Sp-EVs production and intracellular ATP level, underlying a relation between metabolic status and EV biogenesis. Functionally, Sp-EVs promoted biofilm formation in both S. pneumoniae and Streptococcus pyogenes. Sp-EVs isolated under glucose-rich conditions enhanced S. pneumoniae biofilms, whereas Sp-EVs from glucose-poor conditions strongly stimulated S. pyogenes biofilm formation. Conclusions These findings underscore the role of host and environmental cues in shaping pneumococcal EV production, composition, and function, highlighting their potential involvement in metabolic adaptation and interspecies interactions.

Microbial dysbiosis in inflammatory bowel disease (IBD) reduces intestinal butyrate levels, compromising epithelial barrier integrity and enabling overgrowth of opportunistic pathogens such as Candida albicans. Here, we present a human immunocompetent colitis-on-chip model (CooC) that mimics key features of inflamed gut mucosa, including DSS-induced epithelial damage and C. albicans tissue invasion. Using this model, we uncover dual protective roles of microbiota-derived butyrate: (i) stabilization of epithelial adherens junctions and promotion of epithelial renewal, thereby restricting fungal invasion; and (ii) modulation of macrophage function to enhance antifungal activity while attenuating inflammasome-mediated inflammation. Butyrate pretreatment preserves barrier function, limits fungal translocation, and promotes macrophage viability through the inhibition of histone deacetylase (HDAC) and the suppression of NLRP3 inflammasome activation. These findings position butyrate as a key metabolite in orchestrating epithelial-immune defense against fungal exacerbation in colitis, supporting its therapeutic and preventive potential in restoring mucosal resilience in IBD.

Neutrophils effectively eliminate Candida albicans from human blood, but a subset of fungal cells escapes clearance and remains extracellular and viable. Here we show that this evasion is independent of known immune-escape traits of C. albicans. Instead, neutrophil-derived extracellular vesicles (EVs) enriched in antimicrobial proteins and neutrophil surface markers (CD66b, CD45, CD63, and complement receptors CR1, CR3 and CR4) promote this state. Isolated EVs bound to C. albicans preferentially in a complement-dependent manner, and this binding was partially inhibited by anti-CD11b, supporting CR3 involvement. Despite their antimicrobial cargo, EVs did not impair fungal growth. Instead, EV coating reduced neutrophil phagocytosis in purified-cell and whole-blood settings. These findings reveal a dual role for neutrophil-derived EVs at the host-pathogen interface: although enriched for innate effector molecules with potential antifungal activity, their deposition on C. albicans does not impair growth but is associated with reduced phagocytosis and maintenance of an extracellular population.

Antimicrobial resistance and tolerance pose escalating global health threats, necessitating reproducible and accessible tools for antimicrobial susceptibility testing (AST). While disk diffusion assays (DDAs) and Epsilometer tests (Etests) are widely used, there are limited open-source tools to analyze them. We present J-AST, a free, open-source, web-based platform for analyzing both DDAs and Etests. It provides automated and interactive annotation of regions of interest and metadata management, and quantifies microbial resistance and tolerance. J-AST outputs correlate strongly with those of existing tools, and equivalent DDA and Etest results correlate strongly with each other. The automated MIC detection achieved >90% agreement with manual readouts. J-AST is deployable both as desktop software and cloud service, unifies automated analysis with interactive review, and advances both fundamental research and clinical AST workflows.

BACKGROUND AND AIMS:Ulcerative colitis (UC) is characterized by disruptions of the gut microbiome and an exaggerated mucosal immune response in genetically susceptible individuals. Alterations in the composition of the intestinal metabolome associated with dysbiosis can trigger chronic inflammation. However, it remains unclear whether microbial dysbiosis is the cause or consequence of chronic mucosal inflammation. To address this gap, we aimed to investigate the potential pro-inflammatory effects of sterile fecal microbiome filtrate (FMF) using a microphysiological, immunocompetent intestine-on-chip (IoC) model. METHODS:Sterile FMF from UC patients with active disease (n = 6) or in remission (n = 4) and non-UC individuals (n = 5) were applied to IoC models. Cytokine responses of the epithelial and endothelial compartments were assessed after 24  h, 48  h, and 72  h of incubation, while barrier permeability was evaluated after a period of 72 h. An artificial intelligence-driven image analysis pipeline was developed to quantify structural alterations of the epithelial tissue, including damage and thickness, as well as endothelial and immune cell densities in the IoC model in response to FMF exposure. RESULTS:FMF from active UC patients significantly increased proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-23, and MCP-1) in the vascular IoC compartment in a time-dependent manner. In contrast, FMF from non-UC or UC patients in remission had no significant impact on the proinflammatory cytokine response compared to untreated media control. Luminal-vascular permeability was increased following the FMF treatment regardless of its origin. Image-based analysis revealed increased epithelial tissue damage and reduced tissue thickness following FMF exposure, alongside decreased endothelial cell density and altered macrophage morphology, independent of UC disease activity. CONCLUSIONS:FMF from UC patients with active disease induces a robust proinflammatory cytokine response in the IoC model, suggesting that UC-associated FMF-derived factors may contribute to the initiation of inflammatory processes relevant to UC pathogenesis. These findings are derived from a simplified intestinal barrier model and require further mechanistic and physiological validation. While image analysis revealed no significant microarchitectural differences among the three FMF groups, the pipelines established standardized metrics to evaluate the impact of FMF-derived factors on intestinal tissue integrity and immune responses, providing a framework for future IoC-based research in UC.

Abstract Background Whether the lung microbiome represents a stable microbial colonization or a transient ecosystem shaped by continuous microbial turnover and controlled by host immunity remains unresolved. The murine lung microbiome largely consists of species from the former Lactobacillus genus with Ligilactobacillus murinus as a dominant species, bacterial genera such as Streptococcus , Staphylococcus , Mammaliicoccus , Enterococcus and other less frequently detected bacteria. Here, we directly addressed the question of persistence and host interaction of a dominant murine lung commensal in vivo and focused on the host immune response towards lung commensal bacteria. Results We developed a transformation strategy for stable genomic integration of a green fluorescent protein (GFP)-encoding gene to track the fate of a lung bacterium. Following intranasal administration of GFP-labeled L. murinus in mice, bacteria were readily detected in the lungs at early time points but declined rapidly and became undetectable after 72 hours, as determined by quantification of viable bacteria and qPCR. Flow cytometry and fluorescence imaging revealed efficient uptake of GFP-labeled bacteria by lung phagocytes. These findings indicate that even dominant members of the murine pulmonary microbiota normally detected at low abundances are transiently present in the lungs without causing infection. We further analyzed the effects of moderate and high bacterial concentrations. While moderate bacterial loads were efficiently controlled without clinical effects, high concentrations induced severe lethargy, indicating a threshold-dependent host response. Finally, we demonstrated that pulmonary commensals such as L. murinus , Staphylococcus xylosus , and Mammaliicoccus sciuri , as well as conidia of the opportunistic lung pathogen Aspergillus fumigatus , are phagocytosed at comparable rates in macrophage assays. Conclusions Our data demonstrate that even lung-adapted bacterial species fail to establish stable colonization and are instead subject to rapid immune-mediated elimination contributing to the maintenance of a low microbial burden in the lungs. While this homeostatic balance supports health, elevated bacterial loads trigger immune activation and, at high levels, lead to health deterioration. Together, these results support a model of a highly dynamic and transient lung microbiome, maintained by continual microbial immigration rather than long-term colonization. Accounting for the lung microbiome dynamics is essential for understanding host-microbiota interactions and respiratory health.

Abstract The regulation of human hematopoietic stem cell (HSC) function within its native bone marrow microenvironment remains poorly understood due to the limitations of existing humanized models. Here, we present a non-conditioned human HSC xenotransplantation platform that serves as a physiologically relevant in vivo surrogate to study these complex cellular interactions. Using this system, we uncover a dynamic, cross-species communication between human HSCs and the murine niche, revealing a profound cellular and molecular plasticity of the bone marrow microenvironment in response to humanization. Upon engraftment, platelet-derived growth factor receptor alpha positive (Pdgfra + ) mesenchymal stromal cells (MSCs) undergo significant numerical expansion and a major transcriptional shift, transitioning from a mixed adipo- and osteo-primed state toward a leptin receptor positive (Lepr + ) predominantly adipo-primed, hematopoiesis-supporting signature. Functional validation demonstrates that this niche plasticity is a critical determinant of stem cell engraftment: the targeted depletion of Lepr + MSCs or the genetic deletion of stem cell factor results in the rapid mobilization and lack of engraftment of human HSCs, respectively. Our findings establish niche plasticity as a primary regulator of human HSC function and demonstrate the utility of this cross-species platform as a modular genetic toolbox for precise in vivo engineering of the bone marrow microenvironment. Ultimately, this adaptable system provides a powerful framework for elucidating human stem cell biology and advancing bone marrow transplantation therapies.

Bacterial and human cells produce extracellular vesicles (EVs) in response to diverse stimuli, e.g., toxins, oxidative stress, nutrient depletion, or high cell density. Here, we describe a cocultivation platform that allows recovery of mixed extracellular vesicles (mix-EVs) produced simultaneously by both cell types. We investigated interactions between Gram-positive and Gram-negative bacteria (Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, and Neisseria meningitidis) and human peripheral blood mononuclear cells (PBMCs). The production of the mix-EVs population decreased with higher bacterial concentrations. Exposing PBMCs to mix-EVs repressed the general transcriptomic signature, in contrast with a significant upregulation generated by single bacterial-EVs. However, mix-EVs-derived IL-1β upregulation was confirmed at the protein level. Inhibition experiments showed that IL-1β production involved TLR2 and TLR4 signaling, acting through IRAK-1 and TRAF6 related pathways. This approach provides a new platform for the study of EVs at the pathogen-host interface and presents mechanistic insights into the effect of EVs on an infected host.

Influenza viruses (IVs) represent a significant global health issue, capable of causing seasonal epidemics and occasional pandemics with substantial morbidity and mortality. The emergence of viral resistance further complicates treatment strategies. In this study, induced pluripotent stem cell-derived human alveolar type II (iAT2) cells are used to model influenza A virus (IAV) infection and to assess antiviral responses. Cultured at an air-liquid interface (ALI) in transwell systems, iAT2 cells recapitulate key features of the alveolar epithelium and support productive IAV replication. Upon infection, iAT2 cells mounted an antiviral transcriptional response and exhibited sensitivity to oseltamivir treatment, consistent with its established in vivo efficacy. Together, these findings highlight the utility of iAT2 cells as a scalable, physiologically relevant in vitro model for influenza research and antiviral drug testing. Future applications may include the evaluation of emerging viral strains and the development of personalized antiviral therapies.

The progressive increase in microbial resistance to antibiotics is a global health threat that requires solutions for rapid and reliable determination of antibiotic susceptibility in order to select appropriate antibiotics and dosages prior to treatment. We have established a screening platform that enables the detection of cell growth after just a few cell divisions. Our methodological approach for a robust phenotypic antibiotic susceptibility testing is based on the innovative combination of three cutting-edge technologies: (i) a high-throughput microfluidic platform where individual bacterial cells are encapsulated in picoliter-sized droplets, (ii) a 2D angle-resolved light scattering sensor to perform label-free hourly screening of the droplets, and (iii) a computational image analysis approach based on convolutional neural networks to evaluate the dynamics of microbial growth in droplets. For the gram-positive Staphylococcus aureus and gram-negative Escherichia coli, we demonstrate that microbial growth in droplets can be successfully detected within one to two hours. Furthermore, the potential of this platform for rapid phenotypic antibiotic susceptibility testing is demonstrated as a proof-of-concept with the clinically relevant bacterium S. aureus under various concentrations of the antibiotic tetracycline. Notably, we reach a robust phenotypic decision regarding the sensitivity to this antibiotic within two hours.

INTRODUCTION:There is an urgent need for rapid, high-throughput phenotypic antimicrobial susceptibility testing (AST) capable of assessing a microbial sample's susceptibility to multiple antibiotics. OBJECTIVES:In this study, we have established a multiplexed rapid AST platform that employs droplet microfluidics for high-throughput single-cell based analysis, 2D angle-resolved light scattering for growth detection, and fluorescence detection via optical fibers to identify the antibiotic condition within each droplet. METHODS:For this, multiple antibiotic conditions are coded with fluorescence dyes and encapsulated with single cells to enable the testing of multiple antibiotics in a single experiment. We utilize convolutional neural networks (CNNs) and statistical models to assess the growth of various Staphylococcus aureus strains and determine the probability of susceptibility to different antibiotics. RESULTS:Our platform achieved a 95% categorical agreement with the disc diffusion reference method after just three hours of incubation, demonstrating the same level of accuracy as the established VITEK 2 system for the tested strains and antibiotics. Notably, our platform reduced the incubation time by 5-11 h compared to VITEK 2 and by 13-17 h compared to the gold standard disc diffusion method. CONCLUSIONS:With the presented innovations, our technology takes a big step towards realizing true phenotypic determination of antibiotic resistance profiles for timely antimicrobial treatment decisions.

Activating internal tandem duplications (ITD) in the juxtamembrane domain of receptor tyrosine kinase FLT3 occur frequently in patients with acute myeloid leukemia (AML). Constitutive active FLT3-ITD mutations induce aberrant signaling and promote leukemic cell transformation. Inactivation of the attenuating receptor protein tyrosine phosphatase CD45 (PTPRC) in FLT3-ITD mice resulted in the development of a severe hematopoietic phenotype with characteristics of AML. In addition, abnormal bone structures and ectopic bone formation were observed in these mice, suggesting a previously unknown role of FLT3 to control bone development and remodeling. While Ptprc knockout and Flt3-ITD mutant mice showed a largely normal bone microarchitecture, micro-CT analysis of femurs from Flt3-ITD Ptprc knockout mice revealed trabecularization of the cortical bone. This resulted in increased trabecular bone volume at the metaphysis, while the cortical bone at the diaphysis was thinner and less dense. In the metaphysis, severely reduced osteoclast and osteoblast numbers were observed. Reduced capacity of ex vivo differentiation of CD11b-positive bone marrow stem cells to mature osteoclast was accompanied by their abnormal morphology and reduced size. Transcriptome analysis revealed reduced expression of osteoclastogenic genes. Unexpectedly, cumulative resorption activity of osteoclasts was increased. Size and structure of resorption pits of differentiated osteoclasts remained similar to those observed in osteoclast cultures derived from control animals. Enhanced proliferation of cells in osteoclast cultures derived from FLT3-ITD-expressing mice was mediated by increased expression of STAT5 target genes. Transcriptome analysis of differentiated osteoclasts showed dysregulated signaling pathways influencing their differentiation as well as the coupling of bone resorption and formation. Taken together, inactivation of attenuating CD45 in mice expressing oncogenic FLT3-ITD resulted in marked abnormalities of the osteo-hematopoietic niche, which can be explained by aberrant STAT5 activation. Acute myeloid leukemia (AML) is frequently linked to mutations in the receptor tyrosine kinase FLT3. These mutations, called FLT3-ITD, cause the gene to become constitutive active, leading to abnormal cell behavior and cancer development. While investigating Flt3-ITD mutant mice corresponding to human AML patients with FLT3 mutations, we previously found that these mice had an unexpected phenotype of bone resorption when CD45/Ptprc, a phosphatase that normally regulates FLT3 activity, was additionally knocked out. In the present study, we investigated the details of this bone resorption phenotype. MicroCT scans revealed unusual bone patterns like thinner cortical areas and increased spongy bone structures in other areas. These changes were linked to fewer bone-building cells (osteoblasts) and bone-resorbing cells (osteoclasts). While remaining osteoclasts appeared to smaller in size, they behaved abnormally, showing increased overall activity. Further analysis revealed that these changes were driven by altered signaling pathways linked to an overactive protein, STAT5, which is a known target of FLT3-ITD. Ptprc knockout without FLT3-ITD background did not lead to any of the observed changes. Thus, this study highlights a previously unknown capacity of AML-associated FLT3 mutations to regulate bone remodeling offering new insights how the bone and blood systems are interconnected.

Understanding the complex interplay between host and pathogen during infection is critical for developing diagnostics and improving therapeutic interventions. Among the diverse arsenal employed by the host, antimicrobial peptides (AMP) play a key role in the defense against pathogens. We propose an immune evasion mechanism termed "Complex-mediated evasion" (CME), that allows pathogens to protect themselves against AMP and investigate it through mathematical modeling and computer simulations. To achieve CME, we hypothesize that the pathogen secretes defense molecules that bind AMP. When bound within the complex, AMP are unable to harm the pathogen. Due to molecular gradients, complexes may diffuse away from the pathogen, enhancing the protective effect of the mechanism by decreasing the concentration of AMP in the vicinity of the pathogen. We establish a mathematical model to (i) explore the sensitivity of the mechanism to various parameters and (ii) simulate the immune evasion of the human-pathogenic fungus Candida albicans.

The lung microbiome has recently gained attention for potentially affecting respiratory viral infections, including influenza A virus, respiratory syncytial virus (RSV) and SARS-CoV-2. We will discuss the complexities of the lung microenvironment in the context of viral infections and the use of organ-on-chip (OoC) models in replicating the respiratory tract milieu to aid in understanding the role of temporary microbial colonization. Leveraging the innovative capabilities of OoC, particularly through integrating gut and lung models, opens new avenues to understand the mechanisms linking inter-organ crosstalk and respiratory infections. We will discuss technical aspects of OoC lung models, ranging from the selection of cell substrates for extracellular matrix mimicry, mechanical strain, breathing mechanisms and air–liquid interface to the integration of immune cells and use of microscopy tools for algorithm-based image analysis and systems biology to study viral infection in vitro. OoC offers exciting new options to study viral infections across host species and to investigate human cellular physiology at a personalized level. This review bridges the gap between complex biological phenomena and the technical prowess of OoC models, providing a comprehensive roadmap for researchers in the field.

Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear. This study identified protein kinase C-α (PKCα) as a novel target for managing excretory liver function during sepsis. Using a preclinical murine sepsis model, we found that both PKCα knockout and the use of a PKCα-inhibitor midostaurin successfully restored liver function without hindering the host’s response or ability to clear the pathogen, highlighting PKCα’s vital role in excretory liver failure. In septic animals, both approaches significantly boosted survival rates. Midostaurin is the clinically approved active pharmaceutical ingredient in Rydapt, approved for the adjuvant treatment of FTL3-mutated AML. Here, it reduced plasma bile acids and related inflammation in those patients, opening a translational avenue for therapeutics in sepsis. Conclusively, our research underscores the significance of PKCα in controlling excretory liver function during inflammation. This suggests that targeting this protein could restore liver function without compromising the immune system, thereby decreasing sepsis mortality and supporting the recent paradigm that the liver is a hub for the host response to infection that might, in the future, result in novel host-directed therapies supporting the current state-of-the-art intensive care medicine in patients with sepsis-associated liver failure.

The ability of pathogens to evade phagosomal killing is critical for their pathogenicity. Previously, we had identified the HscA effector protein in the clinically important fungal pathogen Aspergillus fumigatus , which redirects conidia-containing phagosomes from the degradative to the non-degradative pathway. Here, we discovered a pathogenic form of this surface protein, determined by a single tyrosine residue (Y) at position 596, which is lacking in most of fungi analyzed, that have a leucine (L) instead. Y596 enables HscA to penetrate the phagosomal membrane. In line, the introduction of a single L-to-Y exchange in the orthologous Ssb protein of Saccharomyces cerevisiae enabled the protein to penetrate phagosomal membranes that was reduced by deletion of one of the two Y-encoding SSB genes in the pathogenic fungus Candida glabrata . These data suggest a convergent evolution of HscA/Ssb proteins among human-pathogenic fungi and that a single amino acid exchange determines a virulence factor. ### Competing Interest Statement The authors have declared no competing interest.