Biology subjects

Pees, B.

Publications and source records attributed to Pees, B..

8 recordsLinked to original sources

bioRxiv2026

A symbiont-derived biosurfactant couples bacterial surface behavior and host peristalsis to control colonization

Hosts must control symbiont abundance to ensure stable associations with their beneficial microbes, while also minimizing potentially harmful unrestricted microbial proliferation. Yet, the microbial stimuli and involved host responses that shape this colonization control, are usually unknown, in spite of their central role in shaping host-microbe and, more broadly, host-microbiota interactions. Here, using the natural association between Caenorhabditis elegans and its symbiont Pseudomonas lurida MYb11, we combine an unbiased bacterial genetic screen with a host response reporter to identify the biosurfactant massetolide as a key regulator of host-microbe interaction. Our subsequent host functional genetic analyses revealed that massetolide triggers host TGF-beta and serotonergic signaling to promote intestinal peristalsis, limiting colonization. Indeed, massetolide deficiency enhances colonization, while its presence specifically facilitates serotonin-dependent expulsion. Together, our findings reveal a symbiont-derived biosurfactant that links host neuroimmune control of intestinal peristalsis with bacterial susceptibility to expulsion, coupling host and microbial physiology to regulate symbiont abundance.

microbiology↗

bioRxiv2026

Evolutionary trade-offs between antimicrobial resistance and virulence in Pseudomonas aeruginosa

Antibiotics impose strong selection on bacteria, resulting in the emergence and spread of antimicrobial resistance. To date, the consequences of resistance evolution for other traits, especially virulence as a key life-history characteristic of high medical relevance remain poorly understood. A central limitation of existing work is reliance on clinical isolates with complex evolutionary histories, hindering causal inferences on resistance-virulence relationships. Such causal information is critical for our understanding of the distribution of resistance-associated evolutionary trade-offs, which may additionally guide optimization of treatment designs. The objectives of our study are to address these knowledge gaps using an experimental evolution framework with the human pathogen Pseudomonas aeruginosa. We quantified changes in resistance, life-history characteristics, in-vivo virulence with a Caenorhabditis elegans infection model, and whole genome sequences for bacterial clones, which had been independently evolved under three antibiotics with distinct cellular targets. We found that the resistance-virulence trade-off depended on the used antibiotic and was additionally driven by the underlying evolutionary path to resistance. Evolved resistance to the fluoroquinolone ciprofloxacin correlated positively with virulence, dependent on genetic changes in either the antibiotic target or efflux regulation. Conversely, evolved resistance to piperacillin/tazobactam, a {beta}-lactam/{beta}-lactamase inhibitor combination, was negatively correlated with virulence, contingent on the coincidental spread of resistance mutations and a large genomic deletion, containing numerous virulence genes. Lastly, evolved resistance to the aminoglycoside streptomycin led to only minor virulence changes. Overall, these antibiotic-specific evolutionary trajectories challenge the assumption of a universal resistance-virulence trade-off and demonstrate that antibiotic choice itself shapes pathogen virulence potential. Significance StatementAntimicrobial resistance and bacterial virulence are typically studied in isolation, yet they are shaped by the same evolutionary pressures and may directly compete for cellular resources. We addressed a fundamental but unresolved question: does evolution of resistance to an antibiotic make a pathogen more or less dangerous to a host? By characterizing experimentally evolved Pseudomonas aeruginosa, a leading cause of drug-resistant infections, we show that the answer depends on which antibiotic drove resistance. A positive resistance-virulence relationship occurred upon adaptation to a fluoroquinolone antibiotic, whereas it was negative upon {beta}-lactam resistance, and unchanged upon aminoglycoside resistance evolution. These antibiotic-specific evolutionary trajectories challenge the assumption of a universal resistance-virulence trade-off and suggest that antibiotic choice shapes pathogen danger beyond drug susceptibility.

evolutionary biology↗

bioRxiv2024

Polyketide synthase-derived sphingolipids determine microbiota-mediated protection against pathogens in C. elegans

Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affect C. elegans tolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.

molecular biology↗

bioRxiv2023

Identification of intestinal mediators of Caenorhabditis elegans DBL-1/BMP immune signaling shaping gut microbiome composition

The composition of the gut microbiome is determined by a complex interplay of diet, host genetics, microbe-microbe competition, abiotic factors, and stochasticity. Previous studies have demonstrated the importance of host genetics in community assembly of the Caenorhabditis elegans gut microbiome and identified a pivotal role for DBL-1/BMP immune signaling in determining the abundance of gut Enterobacteriaceae, in particular of the genus Enterobacter. However, the effects of DBL-1 signaling on gut bacteria were found to depend on its activation in extra-intestinal tissues, suggesting that yet unidentified intestinal factors must mediate these effects. In the present study, we used RNA-seq gene expression analysis of wildtype, dbl-1 and sma-3 mutants, and dbl-1 over-expressors to identify genes regulated by DBL-1/BMP signaling that take part in interactions with gut commensals. Following confirmation of several putative targets by qRT-PCR, we carried out colonization experiments with respective mutants raised on monocultures as well as on defined bacterial communities. These experiments identified five intestinal DBL-1/BMP targets, predicted to be secreted, that showed increased Enterobacteriaceae abundance compared to wildtype. The extent of increases was for the most part lower than those seen in DBL-1 pathway mutants, suggesting that identified mediators are components of a DBL-1-regulated antibacterial cocktail, which may additively contribute to shaping of gut microbiome composition. IMPORTANCECompared to the roles of diet, environmental availability, or lifestyle in determining gut microbiome composition, that of genetic factors is the least understood and often underestimated. The identification of intestinal mediators acting downstream of DBL-1/BMP signaling to control enteric bacteria, describes a cocktail of effectors with distinct molecular functions, thus offering a glimpse into the genetic logic of microbiome control as well as a list of targets for future exploration of this logic.

microbiology↗

bioRxiv2023

An Enterobacteriaceae bloom in aging animals is restrained by the gut microbiome

The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of C. elegans to highlight trends shared among individuals, and employing NextGen sequencing, CFU counts and fluorescent imaging to characterize age-dependent changes in worms raised in different microbial environments, we identified an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormachei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its detrimental potential for increasing susceptibility to infection. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

physiology↗

bioRxiv2023

The C. elegans proteome response to two protective Pseudomonas symbionts

The C. elegans natural microbiota isolates Pseudomonas lurida MYb11 and Pseudomonas fluorescens MYb115 protect the host against pathogens through distinct mechanisms. While P. lurida produces an antimicrobial compound and directly inhibits pathogen growth, P. fluorescens MYb115 protects the host without affecting pathogen growth. It is unknown how these two protective microbes affect host biological processes. We used a proteomics approach to elucidate the C. elegans response to MYb11 and MYb115. We found that both Pseudomonas isolates increase vitellogenin protein production in young adults, which confirms previous findings on the effect of microbiota on C. elegans reproductive timing. Moreover, the C. elegans responses to MYb11 and MYb115 exhibit common signatures with the response to other vitamin B12-producing bacteria, emphasizing the importance of vitamin B12 in C. elegans-microbe metabolic interactions. We further analyzed signatures in the C. elegans response specific to MYb11 or MYb115. We provide evidence for distinct modification in lipid metabolism by both mutualistic microbes. We could identify activation of host pathogen defense responses as MYb11-specific proteome signature and provide evidence that the intermediate filament protein IFB-2 is required for MYb115-mediated protection. These results indicate that MYb11 not only produces an antimicrobial compound, but also activates host antimicrobial defenses, which together might increase resistance to infection. In contrast, MYb115 affects host processes such as lipid metabolism and cytoskeleton dynamics, which might increase host tolerance to infection. Overall, this study pinpoints proteins of interest that form the basis for additional exploration into the mechanisms underlying C. elegans microbiota-mediated protection from pathogen infection and other microbiota-mediated traits.

molecular biology↗

bioRxiv2019

The functional repertoire encoded within the native microbiome of the model nematode Caenorhabditis elegans

The microbiome is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of the bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiome of the model nematode Caenorhabditis elegans. We integrated whole genome sequences of 77 bacterial microbiome members with metabolic modelling and experimental characterization of bacterial physiology. We found that, as a community, the microbiome can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses further revealed that nutrient context can influence how bacteria interact within the microbiome. We identified key bacterial traits that are likely to influence the microbes ability to colonize C. elegans (e.g., pyruvate fermentation to acetoin) and the resulting effects on nematode fitness (e.g., hydroxyproline degradation). Considering that the microbiome is usually neglected in the comprehensive research on this nematode, the resource presented here will help our understanding of C. elegans biology in a more natural context. Our integrative approach moreover provides a novel, general framework to dissect microbiome-mediated functions.

microbiology↗

bioRxiv2019

The inducible response of the nematode Caenorhabditis elegans to members of its natural microbiome across development and adult life

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiome affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematode C. elegans as a tractable, experimental model system and assessed the inducible transcriptome response after colonization with members of its native microbiome. For this study, we focused on two isolates of the genus Ochrobactrum. These bacteria are known to be abundant in the nematodes microbiome and are capable of colonizing and persisting in the nematode gut, even under stressful conditions. The transcriptome response was assessed across development and three time points of adult life, using general and C. elegans-specific enrichment analyses to identify affected functions. Our assessment revealed an influence of the microbiome members on the nematodes dietary response, development, fertility, immunity, and energy metabolism. This response is mainly regulated by a GATA transcription factor, most likely ELT-2, as indicated by the enrichment of (i) the GATA motif in the promoter regions of inducible genes and (ii) of ELT-2 targets among the differentially expressed genes. We compared our transcriptome results with a corresponding previously characterized proteome data set, highlighting a significant overlap in the differentially expressed genes and the affected functions. Our analysis further identified a core set of 86 genes that consistently responded to the microbiome members across development and adult life, including several C-type lectin-like genes and genes known to be involved in energy metabolism or fertility. We additionally assessed the consequences of induced gene expression with the help of metabolic network model analysis, using a previously established metabolic network for C. elegans. This analysis complemented the enrichment analyses by revealing an influence of the Ochrobactrum isolates on C. elegans energy metabolism and furthermore metabolism of specific amino acids, fatty acids, and also folate biosynthesis. Our findings highlight the multifaceted impact of naturally colonizing microbiome isolates on C. elegans life history and thereby provide a framework for further analysis of microbiome-mediated host functions.

evolutionary biology↗