7th joint conference "Joint Microbiology & Infection Conference 2024" of the DGHM and VAAM

Prof. Dr.

Chair

Prof.in

Host-associated microbiomes and microbe-host interactions 2

Microbial oral-gut translocation in inflammatory diseases

How cultivation can help to better understand the gut microbiome in inflammatory bowel disease

TU München

Univ.-Prof. Dr.

Invited Speaker

Invited Talk

The endosymbiont Spiroplasma poulsonii increases Drosophila melanogaster resistance to pathogens by enhancing iron sequestration and melanization

Host-associated microbiomes and microbe-host interactions

Facultative endosymbiotic bacteria, such as Wolbachia and Spiroplasma species, are commonly found in association with insects and can dramatically alter their host physiology. Many endosymbionts are defensive and protect their hosts against parasites or pathogens. Despite the widespread nature of defensive insect symbioses and their importance for the ecology and evolution of insects, the mechanisms of symbiont-mediated host protection remain poorly characterized. Here, we utilized the fruit fly Drosophila melanogaster and its facultative endosymbiont Spiroplasma poulsonii to characterize the mechanisms underlying symbiont-mediated host protection against bacterial and fungal pathogens. Our results indicate a variable effect of S. poulsonii on infection outcome, with endosymbiont-harbouring flies being more resistant to Rhyzopus oryzae, Staphylococcus aureus, and Providencia alcalifaciens, but more sensitive or as sensitive as endosymbiont-free flies to the infections with Pseudomonas species. Further focusing on the protective effect, we identified Transferrin-mediated iron sequestration induced by Spiroplasma as being crucial for the defense against R. oryzae and P. alcalifaciens. In case of S. aureus, enhanced melanization in Spiroplasma-harbouring flies plays a major role in the protection. Both iron sequestration and melanization induced by Spiroplasma require the host immune sensor protease Persephone, suggesting a role of proteases secreted by the symbiont in the activation of host defense reactions. Hence, our work reveals a broader defensive range of Spiroplasma than previously appreciated and adds nutritional immunity and melanization to the defensive arsenal of symbionts. We propose that the mechanisms we have identified here may be of broader significance and could apply to other endosymbionts, particularly to Wolbachia, and potentially explain their protective properties.

Oral Presentation

Non-antibiotic drugs break colonization resistance against pathogenic Gammaproteobacteria

Introduction: Drugs have been shown to be a critical determinant of inter-individual differences in the composition of the human gut microbiome, which is true not only for antibiotics but also for non-antibiotic drugs. We hypothesized that by altering the composition of the microbiome, non-antibiotic drugs open niches and facilitate pathogen colonization in a similar way to antibiotics.Methods: We compared the susceptibility of commensal and pathogenic bacteria to non-antibiotic drugs and found that pathogens have higher drug resistance, which could favor their expansion after treatment. Drugs were selected that inhibited a broad spectrum of commensals while sparing pathogenic Gammaproteobacteria. We then developed the synthetic model community Com20 to screen for drug-microbiome interactions that increase the risk of enteropathogenic infections. To increase microbial complexity, we performed the same experiments with human stool-derived microbial communities. For drug candidates with particularly strong phenotypes, we tested their ability to disrupt colonization resistance and increase the infection risk for Salmonella Typhimurium (S. Tm) in gnotobiotic and SPF mice.Results and Conclusion: Approximately 35% of the &gt;50 drugs from different therapeutic classes we tested increased the abundance of S. Tm in synthetic and human stool-derived communities. This was due to direct effects of non-antibiotics on individual commensals, altered microbial interactions within communities and the potential of S. Tm to exploit different metabolic niches. Non-antibiotic drugs that favored S. Tm expansion in vitro also promoted other enteric pathogens and increased S. Tm loads in gnotobiotic and conventional mice. Our work allows the systematic evaluation and identification of non-antibiotic drugs that break colonization resistance and increase the risk of infection with enteropathogenic bacteria. These findings may inform future strategies to control pathogen proliferation and to assess individual microbiota-drug-pathogen risks.

Professor

Neurotransmitter-producing commensal bacteria at the interface of host metabolism

Introduction. Trace amines (TAs) are neuro-monoamines produced by bacteria and humans mainly by decarboxylation of aromatic amino acids (AAAs). Bacterial AAA decarboxylases (AADCs) are generally specific in substrate preference. Staphylococcal AADC (SadA) is, however, non-specific and decarboxylates tryptophan, tyrosine and phenylalanine to tryptamine, tyramine, and phenethylamine, respectively. It is also able to convert dihydroxy phenylalanine and 5-hydroxytryptophan to dopamine and serotonin. Goals. What are the potential interactions between TA-producing commensal bacteria and the host cells? Materials &amp; methods. The skin microbiome of healthy subjects was examined using shotgun metagenomic and culture-based analyses. The investigation of bacterial adherence and internalization was carried out using the HT-29 cell line. The in vitro and in vivo effects of TAs and TA-producing bacteria on wound healing assays were evaluated in HaCaT cells and in murine model. Results. Metagenomic analysis of the skin microbiota revealed a wide distribution of SadA homologs among at least 7 different phyla, remarkably within the Firmicutes phylum. In culture-based analysis, the AADC activity was found in isolates other than Staphylococcus sp. including Cutibacterium acnes, Corynebacterium sp., and Bacillus sp.. Staphylococcus epidermidis and S. pseudintermedius secrete TAs which trigger their adherence and internalization into human cells by activation of the α2-adrenergic receptor (AR). TAs could accelerate wound healing by antagonizing the b2-AR in keratinocytes which was confirmed in vivo by an application on the wound bed of TAs or a TA-producing S. epidermidis strain. As TAs can activate the wide distributed TA-associated receptors (TAARs) at nanomolar affinities, it is not unexpected to have their wide-range presynaptic "amphetamine-like" effects all over body and brain which we are currently investigating using Parkinson&quot;s and Alzheimer&quot;s mouse models. Conclusion. TA-producing bacteria are ubiquitous in human microbiota which interact with host metabolism through direct stimulation of TAARs. Further studies are required to address more aspects of this interaction.

Raum 12

FG PW (Mikrobiota, Probiotika und Wirt) / FG Mikrobiom / FG Symbiotische Interaktionen

Symposium

Microbiomes: From Sequence-Based Analyses to Active Strains and Molecules (Part I)

(Mini)Symposium

Symposium
Microbiomes: From Sequence-Based Analyses to Active Strains and Molecules (Part I)

Termin

Chair

Thema

Beschreibung

Programm

SymposiumMicrobiomes: From Sequence-Based Analyses to Active Strains and Molecules (Part I)

Termin

Chair

Thema

Beschreibung

Programm

Symposium
Microbiomes: From Sequence-Based Analyses to Active Strains and Molecules (Part I)