Biology subjects

Franz, M.

Publications and source records attributed to Franz, M..

12 recordsLinked to original sources

bioRxiv2026

Microbiota-pathogen interactions after host death:a potential determinant of pathogen evolution

During the lifetime of many animals, the microbiota fulfills multiple functions. After death of their hosts, these microbes contribute to cadaver decomposition, with implications for forensics, fossilization and soil nutrient and microbial community dynamics. Here, we draw attention to the possibility that host microbiota can also influence the evolution of pathogen lifestyles. We hypothesized that competition between microbiota and pathogens after host death can reduce benefits to pathogens of killing and decomposing their host. To test this hypothesis, we conducted infection experiments in which we injected the entomopathogenic bacteria Pseudomonas entomophila into Tenebrio molitor larvae. Our results show that bacterial proliferation after pathogen-induced host death occurs in larvae with strongly reduced microbiota, but not in larvae with intact gut microbiota. Strikingly, we found that gut microbiota can suppress the proliferation of an about 100 times larger pathogen population. In addition, we identified a microbiota member that might have mediated competitive suppression of pathogen proliferation after host death. Taken together, our results support our hypothesis that decomposing host microbiota can effectively compete with pathogens, thereby reducing the fitness of pathogens that kill and then exploit dead hosts. Based on a reanalysis of an existing theoretical model, we conclude that the host microbiota can facilitate the evolution of more benign pathogens that are less likely to kill their host for cadaver exploitation. Thus, our findings highlight the potentially important but so far unexplored possibility that pathogen-microbiota interactions in dead hosts can affect living hosts by influencing the evolution of pathogens lifestyles.

microbiology↗

bioRxiv2026

The danger hypothesis of virulence evolution

Multicellular organisms regularly encounter microbes, which are, however, only rarely pathogenic. Our understanding of this phenomenon is currently restricted due to lacking theory on evolutionary transitions between non-pathogenic and pathogenic microbial lifestyles. Here we addressed this gap by investigating a mathematical model of host-microbe interactions that is based on the danger theory of immunology, which states that danger signals related to host tissue damage play a key role in activating immune responses. We formally implemented this idea by assuming that immune activation increases with costs that microbes cause to their host, and we compared this to scenarios in which immune activation depends only on the presence or load of infecting microbes. Our model analysis revealed that cost-based - but not presence or load-based - immune activation favours the evolution of avirulence and associated non-pathogenic microbial lifestyles. Based on our results, we propose the danger hypothesis of virulence evolution which states that evolution towards avirulence and intermediate virulence are both possible - depending on whether hosts can accurately assess costs generated by microbes. The idea that basic host immune responses can select for avirulence offers a new explanation for why most microbes are not pathogenic to a given host.

evolutionary biology↗

bioRxiv2025

Infection outcomes depend on within-host spatial dynamics

AbstractHost-pathogen interactions can result in stochastic variation in infection outcomes, where the host survives the infection with a persistent bacterial load, clears the infection, or succumbs to death with a high pathogen load. This inter-individual variation is thought to be driven by the speed of immune activation, pathogen virulence and the ability of the pathogen to survive inside the host, but not much is known about whether inter-individual variation in infection outcome could stem from other factors, such as within-host spatial dynamics of the pathogen during infection. Hence, in this study, we used the pathogenic bacterium Providencia burhodogranariea to investigate the effect of body part and site of injection on infection outcomes in Drosophila melanogaster. Although P. burhodogranariea disseminated throughout the body as would be expected for organisms with an open circulatory system, the bacteria localized at lower levels in the abdomen compared to the head and thorax, and they were cleared more quickly in the abdomen. Furthermore, based on our empirical results in combination with a theoretical model, we suggest that terminal infections could be a consequence of damage to the thorax. Our results highlight the role that factors such as injection site and body part can influence the spatial dynamics of the pathogen, which can, in turn, drive the infection outcomes.

immunology↗

bioRxiv2025

Immune-mediated indirect interaction between gut microbiota and bacterial pathogens

BackgroundOrganism survival depends on the ability to orchestrate interactions between the host immune system and gut microbiota in response to pathogenic infections. These tripartite interactions shape pathogen virulence evolution. A key regulator of the immune system and, hence, bipartite interactions (in insects) is the immune deficiency (Imd) pathway, which modulates gut microbiota and pathogens by synthesizing antimicrobial peptides (AMPs). However, whether Imd-dependent AMPs mediate indirect interactions between gut microbiota and pathogens in a tripartite context remains unclear. Using RNAi-mediated knockdown of Tenebrio molitor Relish (TmRelish), we hypothesized that Imd-dependent AMPs influence indirect interaction between Providencia burhodogranaria_B infection and the gut microbiota. ResultsWhile TmRelish-knockdown altered bipartite interactions, disrupting gut microbiota load and composition and increasing pathogen load and virulence through higher host mortality, it did not support our tripartite hypothesis. Instead of Imd-dependent AMPs, gut microbiota and pathogen were influenced by Imd-independent AMPs expression, suggesting alternative regulatory pathways. Nevertheless, our investigations of tripartite interactions showed a positive effect of P. b_B infection on gut microbiota load, while survival analysis further revealed a negative effect of gut microbiota on pathogens infection, suggesting microbiota- mediated immune priming. ConclusionsThese findings suggest that while Imd-dependent AMPs may not mediate tripartite interactions, microbiota-host interactions, such as microbiota-mediated immune priming and changes in microbiota load, can shape infection outcomes. These effects on infection outcomes almost certainly exert important selective pressures on the evolution of bacterial virulence.

immunology↗

bioRxiv2025

Bottlenecks and Resistance Evolution against an Antimicrobial 1 Peptide

Bottlenecks - a severe reduction in population size--are ubiquitous for bacteria in natural systems. For example, during the complete metamorphosis of insects, the gut microbiota is bottlenecked due to a massive secretion of immune effectors such as antimicrobial peptides (AMPs) into the gut. However, the effect of natural bottlenecks on resistance evolution of bacteria to AMPs is currently unknown. Here we measured the bottlenecking of the gut microbiota of G. mellonella, the greater wax moth. Based on these population estimates, we tested in vitro the influence of population size on the adaptation of E. coli against an AMP. We used wild-type E. coli and mutator strains with a 100-fold increase in mutation rates to partly disentangle population size from mutant supply. We found that large E. coli mutator strain populations evolved higher resistance than small populations. Population size, however, did not affect adaptation in wild-type strains. They were not able to evolve resistance under our experimental conditions. This shows that natural bottlenecks can benefit insect hosts by combating the evolution of AMP resistance to their resident gut microbiota, but this should also be applicable to infection in other organisms that use AMPs as an immune defense.

evolutionary biology↗

bioRxiv2021

Decomposing virulence to understand bacterial clearance in persistent infections

Hosts are not always successful at controlling and eliminating a pathogen and the factors causing variation in pathogen clearance are not well understood. To address this problem, we used Drosophila melanogaster to investigate how infections with different bacterial pathogens affects virulence, clearance and persistence. In this context we developed novel hypotheses that focus on how variation in clearance should be related to variation in different components of virulence, where virulence is the infection-related reduction in host fitness. To achieve this, virulence was decomposed into exploitation, i.e., how well bacteria can replicate inside the host, and per parasite pathogenicity (PPP), i.e., the amount of damage per parasite inflicted on the host. We used four bacterial species: Enterobacter cloacae, Providencia burhodogranariea, Lactococcus lactis and Pseudomonas entomophila. The injection doses spanned four orders of magnitude, and survival was followed to estimate virulence. Bacterial load was quantified in live flies during the acute (1-4 days) and chronic (7-35 days) phases of infection, and we tested infection status of flies that had died up to ten weeks post infection. We show that sustained persistent infection and clearance are both possible outcomes for bacterial species across a range of virulence. Bacteria of all species could persist inside the host for at least 75 days, and injection dose partly predicted within-species variation in clearance. Our decomposition of virulence showed that species differences in bacterial virulence could be explained by a combination of variation in both exploitation and PPP. In addition, we found that that higher exploitation leads to lower bacterial clearance, whereas we could not detect any effect of PPP on clearance. The differing effects of exploitation and PPP imply that there can be different means by which variation in virulence is related to clearance, which could critically affect pathogen transmission and the evolution of pathogen virulence. Author summaryFollowing an infection, hosts are not always able to quickly clear the pathogen, and they instead either die or survive with a persistent infection. Such variation is ecologically and evolutionarily important, because it can affect infection prevalence and transmission, and also virulence evolution. But what causes variation in infection outcomes? Here we contribute towards answering this question by investigating infection dynamics in flies infected with one of four bacterial species. We first establish that the bacterial species differ in virulence, i.e., the host death rate after infection. We find that variation in virulence arises because the bacteria differ in the two components of virulence: bacterial growth inside the host (exploitation), and the amount of damage caused per bacterium (per parasite pathogenicity). Furthermore, as early-phase exploitation increases, bacterial clearance later in the infection decreases. This finding can be explained by increasing exploitation leading to increasing clearance costs for the host. Taken together we demonstrate that variation in infection outcomes can be partly explained by how virulence, and its components, relate to the rate of pathogen clearance. We propose that the decomposition of virulence is valuable for understanding variation in infection outcomes - potentially also beyond the interrelation between virulence and clearance.

evolutionary biology↗

bioRxiv2021

The effects of emotional valence and intensity on cognitive and affective empathy after insula lesions

The insula plays a central role in empathy. However, the complex structure of empathic deficits following insular damage is not fully understood. While previous lesion research has shown variable deficits in patients with insular damage on basic discrimination tasks or self-report measures, it is unclear in how far patients with insular damage are impaired in cognitive (CE) and affective empathy (AE) functions depending on valence and arousal of stimuli using an ecologically valid paradigm. In the present study, patients with insular lesions (n = 20) and demographically-matched healthy controls (n = 24) viewed 16 videos (duration: 60 sec each) that varied in terms of valence and emotional intensity. The videos showed a person (target) reporting on a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions they continuously rated their own affect. Mean Squared Error (MSE) assessed deviations between subject and target ratings (CE: deviation between targets and participants ratings of targets emotions; AE: deviation between targets and participants self-ratings of emotion). Patients differed from controls only in negative, low intensity AE, rating their own affective state less negative than the target rated his/her affect. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Our findings provide important insights into the profile of social cognition impairment after insular damage. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context cues by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty, which points to a threshold role of the insula in online ratings of AE.

neuroscience↗

bioRxiv2021

Lateralized deficits in arousal processing after insula lesions: behavioral and autonomic evidence

A large body of evidence ascribes a pivotal role in emotion processing to the insular cortex. However, the complex structure and lateralization of emotional deficits following insular damage are not understood. Here, we investigated emotional ratings of valence and arousal and skin conductance responses (SCR) to a graded series of emotionally arousing scenes in patients with left (n = 10) or right (n = 9) insular damage and in healthy controls (n = 18). We found a significant reduction in overall SCRs, arousal ratings and valence extremity scores in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Additional analyses of correlations between subjective arousal ratings resp. SCR and normative arousal ratings revealed that both lesion groups had evaluative and physiological difficulties to discover changes in stimulus arousal. Although no group differences emerged on overall ratings of valence, analysis of correlations between subjective and normative valence ratings displayed markedly reduced accuracy in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Our findings support the hypothesis that the left and right insulae subserve different functions in emotion processing, potentially due to asymmetrical representations of autonomic information in the left and right human forebrain. The right insula may serve as integral node for sympathetic arousal and cognitive affective processing.

neuroscience↗

bioRxiv2021

Capturing scientific knowledge in computable form

Technological advances in computing provide major opportunities to accelerate scientific discovery. The wide availability of structured knowledge would allow us to take full advantage of these by enabling efficient human-computer interaction. Traditionally, biological knowledge is captured in publications and knowledge bases, however, the information in articles is not directly accessible to computers, and knowledge bases are constrained by finite resources available for manual curation. To accelerate knowledge capture and communication and to keep pace with the rapid growth of scientific reports, we developed the Biofactoid (biofactoid.org) software suite, which crowdsources structured knowledge in articles from authors. Biofactoid is a web-based system that lets scientists draw a network of interactions between genes, their products, and chemical compounds and employs smart-automation to translate user input into a structured language using the expressive power of a formal ontology. The resulting data is shared via public information resources, enabling author-curated knowledge to be appreciated in the context of all existing computable knowledge. Authors of recently published papers across a range of journals have already contributed their pathway information, much of which is novel and extends existing pathway databases into new biological areas. We envision the adoption of Biofactoid for crowdsourced curation by scientists and publishers as part of an ecosystem of tools that accelerate scientific communication and discovery. AvailabilityBiofactoid server at https://biofactoid.org

bioinformatics↗

bioRxiv2020

Comparing proportional and ordinal dominance ranks reveals multiple competitive landscapes in an animal society

Across group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes, and reproductive performance. Studies of how dominance rank affects these outcomes typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here we compare the ability of two dominance rank metrics--ordinal rank and proportional or standardized rank--to predict 20 distinct traits in a well-studied wild baboon population in Amboseli, Kenya. We propose that ordinal rank best predicts outcomes when competition is density-dependent, while proportional rank best predicts outcomes when competition is density-independent. We found that for 75% (15/20) of the traits, one of the two rank metrics performed better than the other. Strikingly, all male traits were better predicted by ordinal than by proportional rank, while female traits were evenly split between being better predicted by proportional or ordinal rank. Hence, male and female traits are shaped by different competitive regimes: males competitive environments are largely driven by density-dependent resource access (e.g., access to estrus females), while females competitive environments are shaped by both density-independent resource access (e.g. distributed food resources) and density-dependent resource access. However, traits related to competition for social and mating partners are an exception to this sex-biased pattern: these traits were better predicted by ordinal rank than by proportional rank for both sexes. We argue that this method of comparing how different rank metrics predict traits of interest can be used as a way to distinguish between different competitive processes operating in animal societies.

animal behavior and cognition↗

bioRxiv2020

Keeping the kids at home can limit the persistence of contagious pathogens in social animals

In social species where offspring are reared together in communal burrows or similar structures, young animals typically do not engage in between-group contact during their development - a behavioural trait we call offspring with restricted between-group contact (ORC). The impact of this trait on the persistence of contagious pathogens that generate lifelong immunity in their hosts is currently unclear. We hypothesize that in populations with ORC, the formation, in groups, of a protective barrier of only recovered adults, prevents the transmission of this type of pathogens to the new susceptible hosts (i.e. young animals), thereby increasing the probability of epidemic fade-out. We implement a spatially implicit individual-based Susceptible-Infected-Recovered (SIR) model for a large range of host and pathogen traits and show that the epidemic fade-out probability is consistently higher in populations with ORC, especially when disease spread is fast (high basic reproduction number R0). We also show that ORC can counteract the cost of group-living in terms of disease risk to a greater extent than variation in other traits. We discuss our findings in relation to herd immunity and outline how they could be used to implement efficient management measures such as vaccinations.

ecology↗

bioRxiv2019

Pathway Commons: 2019 Update

Pathway Commons (https://www.pathwaycommons.org) is an integrated resource of publicly available information about biological pathways including biochemical reactions, assembly of biomolecular complexes, transport and catalysis events and physical interactions involving proteins, DNA, RNA, and small molecules (e.g., metabolites and drug compounds). Data is collected from multiple providers in standard formats, including the Biological Pathway Exchange (BioPAX) language and the Proteomics Standards Initiative Molecular Interactions format, and then integrated. Pathway Commons provides biologists with (1) tools to search this comprehensive resource, (2) a download site offering integrated bulk sets of pathway data (e.g., tables of interactions and gene sets), (3) reusable software libraries for working with pathway information in several programming languages (Java, R, Python, and Javascript), and (4) a web service for programmatically querying the entire dataset. Visualization of pathways is supported using the Systems Biological Graphical Notation (SBGN). Pathway Commons currently contains data from 22 databases with 4,794 detailed human biochemical processes (i.e., pathways) and [~]2.3 million interactions. To enhance the usability of this large resource for end-users, we develop and maintain interactive web applications and training materials that enable pathway exploration and advanced analysis.

bioinformatics↗