Biology subjects

Unterweger, D.

Publications and source records attributed to Unterweger, D..

7 recordsLinked to original sources

bioRxiv2025

Resistance variation and bacterial interactions shape the adaptation of a genetically diverse bacterial population to antimicrobial treatment

Bacterial infections are often polymicrobial and subject to the evolution of antimicrobial resistance (AMR). Existing knowledge on AMR in such polymicrobial infections usually relies on observational patient data, for which cause-effect relationships are difficult to infer, or on studying interactions between different bacterial species, ignoring the commonly encountered variation within species. Here, we therefore asked how mixed populations with strains from the same species evolve under antibiotic treatment. We used a genetically diverse population of the high-risk human pathogen Pseudomonas aeruginosa, and first identified strain variation in both AMR and pairwise bacteria-bacteria interactions, the latter ranging from beneficial, neutral, to competitive. Using experimental evolution, we subsequently demonstrate that the response to selection by different antibiotic treatments is significantly influenced by AMR strain variation, bacterial interactions, and also spatial population structure. Moreover, de novo AMR evolution was additionally impacted by variation in resistance rates towards the two considered antibiotics. A second evolution experiment emphasized the central role of strain variation and bacterial interactions in determining the evolutionary outcome. We conclude that ecological dynamics in genetically diverse pathogen populations are key for our general understanding of infection characteristics and AMR evolution, and, therefore, deserve particular attention during treatment of polymicrobial infections.

evolutionary biology↗

bioRxiv2023

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.

evolutionary biology↗

bioRxiv2023

T6SS-mediated competitive exclusion among Pantoea agglomerans associated with plants

Establishment of symbiotic interactions with a host habitat depends on colonization success of the microbiome members. One route to success is increasing competitiveness against genotypes having similar adaptations. Many bacteria deploy the type VI secretion system (T6SS) to deliver toxic effector proteins into the cytoplasm of competing cells, whereas the attacking cells are protected from self-intoxication by immunity proteins. While the evolution of antagonistic interactions between species competing for similar niches is expected, the interactions between closely related strains having a similar core genetic makeup, remains understudied. Here we show that the strength of T6SS-mediated competition between closely related P. agglomerans strains is not associated with phylogenetic relatedness and rather depends on their effector and immunity genes repertoire. Annotating the T6SS components in eleven P. agglomerans isolates from wheat seeds, we observed a heterogeneous composition of effector and immunity determinants. Competition experiments further showed profound differences in the strain survival following reciprocal T6SS-mediated interactions. Reconstructing the evolution of T6SS loci across plant-associated P. agglomerans isolates indicates intra-chromosomal recombination as the main driver of effector and immunity gene diversification. Our results provide empirical data on intraspecific interactions during microbiota assembly likely to be at play during colonization of germinating plant seeds.

microbiology↗

bioRxiv2023

Closely related Bacteroides of the murine intestinal microbiota affect each other's growth positively or negatively

The mammalian intestine is a unique ecosystem for thousands of bacterial species and strains. How naturally coexisting bacteria of the microbiota interact with each other is not yet fully understood. Here, we isolated formerly coexisting, closely related strains of the genus Bacteroides from the intestines of healthy, wild-derived mice. The effect of one strain on another strains growth was tested in 169 pairs in vitro. We find a vast diversity of growth promoting and growth inhibiting activities. A strong positive effect was observed between two strains with differing metabolisms. Growth inhibition among a subset of strains was associated with the known bacterial toxin bacteroidetocin B. Across all strains, we observed growth promotion more often than growth inhibition. The effects were independent of two strains belonging to the same or different species. In some cases, one species differed in its effect on another according to host origin. These findings on obligate host-associated bacteria demonstrate that closely related and naturally coexisting strains have the potential to affect each others growth positively or negatively. These results have implications for our basic understanding of host-associated microbes and the design of synthetic microbial communities.

microbiology↗

bioRxiv2022

Bacteroides muris sp. nov. isolated from the cecum of wild-derived house mice

Two bacterial strains, KH365_2T and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative, rod-shaped, strictly anaerobic, and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that both strains were most closely related to Bacteroides uniformis ATCC 8492T. Whole genome sequences of KH365_2T and KH569_7 strains have a DNA G+C content of 46.02% and 46.03% mol, respectively. Most morphological and biochemical characteristics did not differ between the newly isolated strains and classified Bacteroides strains. However, the average nucleotide identity (ANI) and dDNA-DNA hybridization (dDDH) values clearly distinguished the two strains from described members of the genus Bacteroides. Here, we present the phylogeny, morphology, and physiology of a novel species of the genus Bacteroides and propose the name Bacteroides muris sp. nov., with KH365_2T (DSM XXX = CCUG XXX) as type strain.

microbiology↗

bioRxiv2022

Core and accessory effectors of type VI secretion systems contribute differently to the intraspecific diversity of Pseudomonas aeruginosa

Bacteria use type VI secretion systems (T6SSs) to deliver effector proteins into other cells or the extracellular space. Those effectors kill microbes1, manipulate eukaryotic cells2, and sequester nutrients3. Which T6SS-mediated functions are generalisable across bacteria of a species or are specific to particular strains is little known. Here, we use genomics to test for the intraspecific diversity of T6SS effectors in the opportunistic pathogen Pseudomonas aeruginosa. We found effectors that are omnipresent and conserved across strains acting as core effectors, while additional accessory effectors vary. In vitro and in vivo experiments demonstrate different roles of the two types of effectors in bacterial killing and virulence. Further, effectors compose various effector combinations. Within one local population of clinical isolates, we observed 36 combinations among 52 bacterial lineages. These findings show the distinct contribution of T6SS effectors to strain-level variation of a bacterial pathogen and might reveal conserved targets for novel antibiotics.

microbiology↗

bioRxiv2019

Vibrio cholerae Type VI Secretion System Auxiliary Cluster 3 is a Pandemic-associated Mobile Genetic Element

All sequenced Vibrio cholerae isolates encode a contact-dependent type VI secretion system (T6SS) in three loci that terminate in a toxic effector and cognate immunity protein (E/I) pair, allowing for competitor killing and clonal expansion in aquatic environments and the host gut. Recent studies have demonstrated variability in the toxic effectors produced by different V. cholerae strains and the propensity for effector genes to undergo horizontal gene transfer. Here we demonstrate that a fourth cluster, auxiliary cluster 3 (Aux3), encoding the E/I pair tseH/tsiH, is located directly downstream from two putative recombinases and is flanked by repeat elements resembling att sites. Genomic analysis of 749 V. cholerae isolates, including both pandemic and environmental strains, revealed that Aux3 exists in two states: a [~]40 kb prophage-like element in nine environmental isolates and a [~]6 kb element in pandemic isolates. These findings indicate that Aux3 in pandemic V. cholerae is evolutionarily related to an environmental prophage-like element. In both states, Aux3 excises from the chromosome via site-specific recombination to form a circular product, likely priming the module for horizontal transfer. Finally, we show that Aux3 can integrate into the Aux3-naive chromosome in an integrase-dependent, site-specific manner. This highlights the potential of Aux3 to undergo horizontal transfer by a phage-like mechanism, which based on pandemic coincidence may confer currently unknown fitness advantages to the recipient V. cholerae cell. Significance StatementV. cholerae is a human pathogen that causes pandemics affecting 2.8 million people annually (1). The O1 El Tor lineage is responsible for the current pandemic. A subset of non-O1 strains cause cholera-like disease by producing the major virulence factors cholera toxin and toxin co-regulated pilus but fail to cause pandemics. The full set of V. cholerae pandemic factors is unknown. Here we describe the type VI secretion system (T6SS) Aux3 element as a largely pandemic-specific factor that is evolutionarily related to an environmental prophage-like element circulating in non-pathogenic strains. These findings shed light on V. cholerae T6SS evolution and indicate the Aux3 element as a pandemic-enriched mobile genetic element.

microbiology↗