Biology subjects

Van der Henst, C.

Publications and source records attributed to Van der Henst, C..

9 recordsLinked to original sources

bioRxiv2026

A novel nanobody-based approach for targeting heterogeneous Acinetobacter baumannii isolates and closely related pathogenic Acinetobacter spp.

Acinetobacter baumannii is a top-priority, ESKAPE pathogen that poses a major challenge to human health. The pathogen is difficult to combat due to its extensive arsenal of antibiotic resistance and its protective polysaccharide capsule. In addition, A. baumannii isolates are highly heterogeneous, which complicates the development of rapid detection methods or novel targeted therapeutic approaches. Here, we discovered and characterized a new biotechnological tool, the nanobody H7 (NbH7), along with its conserved target, the surface-exposed Omp25 protein of A. baumannii, and elucidated their interaction at the molecular level. Moreover, we demonstrate that NbH7-functionalized magnetic beads enable selective and efficient capture of A. baumannii from bacterial mixtures, including non-pathogenic intestinal bacteria. This provides proof of concept for a new targeting system that remains effective across diverse A. baumannii clinical isolates and capsule types and holds potential for use in diagnostic cell enrichment and targeted therapies.

molecular biology↗

bioRxiv2026

High-resolution species delimitation in Acinetobacter baumannii using a novel Core-Gene Consensus Delimitation approach

Acinetobacter baumannii is a highly adaptable nosocomial pathogen with extensive antibiotic resistance, a disproportionately large accessory genome, and high genomic plasticity. Owing to these features, the World Health Organisation (WHO) classifies A.baumannii as a critical-priority pathogen. In this study, we analyzed 47 isolates from our VUB (Vrije Universiteit Brussel) collection and applied distance-based species-delimitation algorithms - Automatic Barcode Gap Discovery (ABGD) and Assemble Species by Automatic Partitioning (ASAP) - for the first time at the bacterial core-genome scale. By integrating conspecificity matrices, we extended these traditionally single-locus methods into a multi-locus framework, which we term Core-Gene Consensus Delimitation (CGCD). Across a range of gene-level co-occurrence thresholds, CGCD consistently recovered 11 stable groups using both ABGD and ASAP. Larger-scale validation using 856 A. baumannii genomes recovered the same 11 well-separated groups were recovered, demonstrating the robustness and reliability of our clustering approach. Mapping these groups onto a core-genome phylogeny revealed that each group forms a distinct clade, indicating that they represent evolutionarily independent lineages rather than arbitrary clusters. We further constructed a clustering tree based on accessory gene presence-absence patterns. In this tree, only one strain (AB231-VUB) clustered within group 11; otherwise, the groups remained tightly cohesive, sharing characteristic sets of accessory genes. Together, these results show that the groups defined by CGCD are genomically, evolutionarily, and functionally distinct, supporting their interpretation as separate species. Our findings highlight CGCD as a powerful, high-resolution framework for species delimitation. CGCD is threshold-free, gene-based, and universally applicable--the first species-delimitation approach that can be applied across all domains of life, from bacteria to animals and plants.

microbiology↗

bioRxiv2025

The absence of the ompA and type VI secretion system in the successful lineage of Acinetobacter baumannii ST19

Acinetobacter baumannii is an opportunistic pathogen, often multi- to pandrug-resistant, including to last-resort antibiotics such as carbapenems. A. baumannii can acquire DNA through multiple mechanisms including natural competence and conjugation. An active Type VI Secretion System (T6SS), which kills nonkin bacteria and challenges and inhibits the conjugation. The acquisition of resistance genes has helped the spread of resistant clones of A. baumannii, such as those of Sequence Types (STPas), ST1, ST2, ST10, ST15, ST25, ST79 and ST85. While ST1 and ST2 were thoroughly studied, there are new emerging clones whose genetic background facilitating the rise is still unknown or poorly understood. The emergence of Acinetobacter baumannii ST19 first peaked in 2003, coinciding with the Iraq conflict and increased detection among U.S. military personnel. Its prevalence later surged in Georgia and Ukraine, around the onset of the conflict in Ukraine in 2022, associating it with regions affected by military activity. In this study, we have sequenced whole-genome three isolates of A. baumannii ST19 and compared them with further 156 A. baumannii ST19 genomes were obtained from public repositories. In total, 157/159 genomes revealed loss of T6SS locus, which was replaced in 56/157 genomes (35,7%) by {Delta}Tn9 carrying chloramphenicol and {Delta}Tn10 carrying tetracycline resistance genes, and formaldehyde and chlorite resistance genes. Surprisingly, the antibiotic resistance-encoding transposons likely originated from Enterobacteriaceae plasmids. The loss of a functional T6SS in A. baumannii ST19 may potentially facilitate horizontal gene transfer and promoting a cooperative or less competitive lifestyle providing a selective advantage at the population level.

microbiology↗

bioRxiv2024

Pathogen genomic surveillance as a scalable framework for precision phage therapy

Phage therapy is gaining increasing interest in the fight against critically resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here we combine large-scale phylogeographical analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii, a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within six years. As we demonstrate in Eastern Europe, this spatio-temporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of a four-phage cocktail against the most prevalent strain type in both in vitro and in vivo animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy. HighlightsO_LIA few carbapenem-resistant Acinetobacter baumannii types dominate infections worldwide C_LIO_LIPhylogeography reveals stable strain composition of individual countries over a six-year period C_LIO_LIThis spatio-temporal distribution allows preemptive preparation of region-specific phage collections C_LIO_LIA four-phage cocktail is efficacious against the most prevalent strain type in Europe. C_LI

microbiology↗

bioRxiv2024

The polysaccharide capsule of Acinetobacter baumannii affects bacterial adhesion and natural transformation

Acinetobacter baumannii is an important threat worldwide due to its ability to acquire antibiotic resistance and survive harsh conditions. The polysaccharide capsule represents a major virulence and resistance asset. How the capsular polysaccharides barrier impacts bacterial adhesion remains to be investigated in A. baumannii. We characterized capsule mutants of the commonly used AB5075 strain. We assessed how these different capsule mutants adhere to biotic (bacterial and eukaryotic cells) and abiotic surfaces (polystyrene). We confirmed our observations using modern and relevant clinical isolates characterized by different capsule types and capsulation levels. Strains with low capsulation levels systematically depicted increased adhesion compared to capsulated strains, and mucoid isolates showed minimal adhesion. These results show capsule production in A. baumannii affects adhesion to various surfaces. We also determined that the presence/absence of A. baumannii capsule influences its natural transformability. This illustrates the importance of the trade-off of capsule production in A. baumannii.

microbiology↗

bioRxiv2022

Acinetobase: the comprehensive database and repository of Acinetobacter strains.

BackgroundAcinetobacter baumannii is one of the most problematic nosocomial pathogens that can efficiently thrive within hospital settings, mainly due to resistances towards antibiotics, desiccation, disinfectants, human serum and oxidative stress. Recently, increased resistance against last resort antibiotics earns this bacterium the highest priority concern classified by the CDC and the WHO. An obvious hallmark of this bacterium is the high heterogeneity observed amongst A. baumannii isolates, with a limited core genome. This feature complexifies the study of A. baumannii bacteria as an entity, subsequently reflected in a diversity of phenotypes of not only antimicrobial and environmental resistance but also virulence. Main bodyHigh degree of genome plasticity, along with the use of a limited subset of established reference strains, can lead to strain-specific observations, decreasing the global understanding of this pathogenic agent. Phenotypic variability of A. baumannii strains is easily observable such as with the macrocolony morphologies, in vitro and in vivo virulence, natural competence level, production of different capsular polysaccharide structures and cellular densities. Some strains encode an extensive amount of virulence factors while other, including the reference strains, lack several key ones. The lack/excess of genes or specific physiological processes might interfere with in vivo and in vitro experiments, thus providing limited impact on the global understanding of Acinetobacter bacteria as a whole. ConclusionAs an answer to the high heterogeneity amongst A. baumannii strains, we propose a first comprehensive database that includes the bacterial strains and the associated phenotypic and genetic data. This new repository, freely accessible to the entire scientific community, allow selecting the best bacterial isolate(s) related to any biological question, using an efficient and fast exchange platform.

bioinformatics↗

bioRxiv2022

What are the reference strains of Acinetobacter baumannii referring to?

We assembled the whole genome sequence (WGS) of a collection of 43 non-redundant modern clinical isolates and four broadly used reference strains of Acinetobacter baumannii. Comparison of these isolates and their WGS confirmed the high heterogeneity in capsule loci, sequence types, the presence of virulence and antibiotic resistance genes. However, a significant portion of clinical isolates strongly differ when compared to several reference strains in the light of colony morphology, cellular density, capsule production, natural transformability and in vivo virulence. These genetic and phenotypic differences between current circulating strains of A. baumannii and established reference strains could hamper the study of A. baumannii as an entity. The broadly used reference strains led to the current state of the art of the A. baumannii field, however, we propose that established reference strains in the A. baumannii field should be carefully used, because of the high genetic and phenotypic heterogeneities. In this study, we generated a collection of high-quality nucleotide sequences of 43 modern clinical isolates with the corresponding multi-level phenotypic characterizations. Beside the contribution of novel fundamental observations generated in this study, the phenotypic and genetic data, along with the bacterial strains themselves, will be further accessible using the first open access online platform called "Acinetobase". Therefore, a rational choice of modern strains will be possible to select the ones that suit the needs of specific biological questions.

microbiology↗

bioRxiv2021

Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

SynopsisO_ST_ABSObjectivesC_ST_ABSThe spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. MethodsA repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. ResultsThe repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 {micro}M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. ConclusionsWe identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.

microbiology↗

bioRxiv2017

Molecular insights into Vibrio cholerae’s intra-amoebal host-pathogen interactions

Vibrio cholerae, which causes the diarrheal disease cholera, is a species of bacteria commonly found in aquatic habitats. Within such environments, the bacterium must defend itself against predatory protozoan grazers. Amoebae are prominent grazers, with Acanthamoeba castellanii being one of the best-studied aquatic amoebae. We previously showed that V. cholerae resists digestion by A. castellanii and establishes a replication niche within the hosts osmoregulatory organelle. In this study, we deciphered the molecular mechanisms involved in the maintenance of V. choleraes intra-amoebal replication niche and its ultimate escape from the succumbed host. We demonstrated that minor virulence features important for disease in mammals, such as extracellular enzymes and flagellum-based motility, play a key role role in the replication and transmission of V. cholerae in its aqueous environment. This work, therefore, describes new mechanisms that provide the pathogen with a fitness advantage in its primary habitat, which may have contributed to the emergence of these minor virulence factors in the species V. cholerae.

microbiology↗