Biology subjects

Voelz, K.

Publications and source records attributed to Voelz, K..

5 recordsLinked to original sources

bioRxiv2019

A bacterial endosymbiont enables fungal immune evasion during fatal mucormycete infection

Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitious in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this, and the evolutionary drivers underlying the acquisition of virulence mechanisms, are poorly understood. Here we show that a clinical isolate of Rhizopus microsporus contains a Ralstonia pickettii bacterial endosymbiont required for virulence in both zebrafish and mice, and that this endosymbiosis enables secretion of factors that potently suppress growth of the soil amoeba Dictyostelium discoideum, as well as their ability to engulf and kill other microbes. As amoebae are natural environmental predators of both bacteria and fungi, we propose this tri-kingdom interaction contributes to establishing the endosymbiosis, and acquisition of anti-phagocyte activity. Importantly, we show this activity also protects fungal spores from phagocytosis and clearance by human macrophages, and endosymbiont removal renders the fungal spores avirulent in vivo. Together, these findings describe a novel role for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in animals, and suggest a mechanism of virulence acquisition through environmental interactions with amoebae. In briefHow environmental fungi evolved the mechanisms that enable them to cause opportunistic infections in humans is unclear. Here, we identify a novel tri-kingdom interaction, whereby a bacterial endosymbiont, living within a clinical isolate of the ubiquitous environmental fungus Rhizopus microsporus, causes the generation of a secreted activity that blocks the growth and predatory activity of amoebae. We suggest this provides a new evolutionary driver for the establishment of bacterial/fungal endosymbiosis and demonstrate this is critical for fungal pathogenicity in vivo.

microbiology↗

bioRxiv2019

Host-pathogen transcriptomics of macrophages, Mucorales and their endosymbionts: a polymicrobial pas de trois

Mucorales spores, the causative agents of mucormycosis, interact with the innate immune system to cause acute, chronic, or resolving infection. Understanding the factors that influence disease initiation and progression is key to understanding mucormycosis and developing new treatments. Complicating this, mucormycosis can be caused by a number of species that span the Mucorales order and may be host to bacterial endosymbionts. This study sets out to examine the differences between two species in the Mucorales order by characterising their differential interactions with the innate immune system, and their interactions with environmental bacterial endosymbionts. Through a holistic approach, this study examines the transcriptional responses of Rhizopus delemar and Rhizopus microsporus, two of the most commonly diagnosed species, to innate immune cells. This study also examines the immune cell response and assesses the variation in these responses, given the presence or absence of bacterial endosymbionts within the fungi. We see that the fungal response is driven by interaction with innate immune cells. Moreover, the effect of the bacterial endosymbiont on the fungus is species-specific and strongly influences fungal transcription during phagocyte stress. The macrophage response varies depending on the infecting fungal species, and depending on endosymbiont status. Macrophages are better able to survive when germination is inhibited, or upon a pro-inflammatory response. This work reveals species-specific host responses to related Mucorales spores and shows that bacterial endosymbionts have an important role to play by impacting both innate immune cell response, and fungal response when under stress.

microbiology↗

bioRxiv2018

Pseudomonas aeruginosa inhibits Rhizopus microsporus germination through sequestration of free environmental iron

Rhizopus spp are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infection. Key to pathogenesis is the ability of fungal spores to swell, germinate, and penetrate surrounding tissues. Antibiotic treatment in at-risk patients increases the probability of the patient developing mucormycosis, suggesting that bacteria have the potential to control the growth of the fungus. However, research into polymicrobial relationships involving Rhizopus spp has not been extensively explored. Here we show that co-culturing Rhizopus microsporus and Pseudomonas aeruginosa results in the inhibition of spore germination. This inhibition was mediated via the secretion of bacterial siderophores, confirming the essential role of iron for fungal growth. Addition of P. aeruginosa siderophores to R. microsporus spores in the zebrafish larval model of infection resulted in inhibition of fungal germination and reduced host mortality. Therefore, during infection antibacterial treatment may relieve bacterial imposed nutrient restriction resulting in secondary fungal infections.

microbiology↗

bioRxiv2018

Pathways of pathogenicity: The transcriptional stages of germination in the fatal fungal pathogen Rhizopus delemar

Rhizopus delemar is an invasive fungal pathogen, responsible for the frequently fatal disease mucormycosis. Germination, a crucial mechanism by which spores of Rhizopus delemar infect and cause disease, is a key developmental process that transforms the dormant spore state into a vegetative one. Understanding the molecular mechanisms which underpin this transformation may be key to controlling mucormycosis, however the regulation of germination remains poorly understood. This study describes the phenotypic and transcriptional changes which take place over the course of germination. This process is characterised by four distinct stages: dormancy, isotropic swelling, germ tube emergence and hyphal growth. Dormant spores are shown to be transcriptionally unique, expressing a subset of transcripts absent in later developmental stages. A large shift in the expression profile is prompted by the initiation of germination, with genes involved in respiration, chitin, cytoskeleton and actin regulation appearing to be important for this transition. A period of transcriptional consistency can be seen throughout isotropic swelling, before the transcriptional landscape shifts again at the onset of hyphal growth. This study provides a greater understanding of the regulation of germination and highlights processes involved in transforming Rhizopus delemar from a single to a multicellular organism.\n\nImportanceGermination is key to the growth of many organisms, including fungal spores. Mucormycete spores exist abundantly within the environment and germinate to form hyphae. These spores are capable of infecting immunocompromised individuals, causing the disease mucormycosis Germination from spore to hyphae within patients leads to angioinvasion, tissue necrosis and often fatal infections. This study advances our understanding of how spore germination occurs in the mucormycetes, identifying processes we may be able to inhibit to help prevent or treat mucormycosis.

microbiology↗

bioRxiv2017

High-resolution analysis of spatiotemporal virulence gene regulation during food-borne infection with Escherichia coli O157:H7 within a live host

Food-borne infection with enterohemorrhagic Escherichia coli (EHEC) is a major cause of diarrheal illness in humans, and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food-chain through contaminated meat, dairy, or vegetables. However, how EHEC transitions from the transmission vector to colonizing the intestinal tract, and how virulence-specific genes are regulated during this transition, is not well understood. Here, we describe the establishment of a vertebrate model for food-borne EHEC infection, using the protozoan Paramecium caudatum as a vector and the zebrafish (Danio rerio) as a host. At 4 days post fertilization, zebrafish have a fully developed intestinal tract, yet are fully transparent. This allows us to follow intestinal colonization, microbe-host cell interactions, and microbial gene induction within the live host and in real time throughout the infection. Additionally, this model can be adapted to compare food- and water-borne infections, under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, the zebrafish allows for investigation of factors affecting shedding and transmission of bacteria to naive hosts. High-resolution analysis of EHEC gene expression within the zebrafish host emphasizes the need for tight transcriptional regulation of virulence factors for within-host fitness.\n\nIMPORTANCEEnterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen which can cause diarrhea, vomiting and in some cases, severe complications such as kidney problems in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food-chain through contaminated meat, dairy and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study food-borne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Using the zebrafish host, we can follow the bacterial infection cycle in real time, and gain important information regarding bacterial physiology and microbe-host interactions. This will allow us to identify potential new targets for infection control and prevention.

microbiology↗