Message

List of publications

Please find below my published articles in chronological order. Links to pubmed (PMID) and to Google Scholar are provided.

A full list of my publications can also be found here:

http://scholar.google.com/citations?hl=nl&user=VHHhpoAAAAAJ&sortby=pubdate&view_op=list_works&pagesize=100

 

(Shared) first authors are marked by *.

 

 

 

Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization

Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization

MBio. 2016 Aug 2;7(4). pii: e01173-16. doi: 10.1128/mBio.01173-16.

Elena Capel, Aldert L Zomer, Thomas Nussbaumer, Christine Bole, Brigitte Izac, Eric Frapy, Julie Meyer, Haniaa Bouzinba-Ségard, Emmanuelle Bille, Anne Jamet, Anne Cavau, Franck Letourneur, Sandrine Bourdoulous, Thomas Rattei, Xavier Nassif, Mathieu Coureuil

Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization.

IMPORTANCE: Meningococcal meningitis is a common cause of meningitis in infants and adults. Neisseria meningitidis (meningococcus) is also a commensal bacterium of the nasopharynx and is carried by 3 to 30% of healthy humans. Under some unknown circumstances, N. meningitidis is able to invade the bloodstream and cause either meningitis or a fatal septicemia known as purpura fulminans. The onset of symptoms is sudden, and death can follow within hours. Although many meningococcal virulence factors have been identified, the mechanisms that allow the bacterium to switch from the commensal to pathogen state remain unknown. Therefore, we used a Tn-seq strategy coupled to high-throughput DNA sequencing technologies to find genes for proteins used by N. meningitidis to specifically colonize epithelial cells and primary brain endothelial cells. We identified 383 genes and 8 intergenic regions containing sRNAs essential for growth and 288 genes and 33 intergenic regions containing sRNAs required specifically for host cell colonization.

Advances and perspectives in computational prediction of microbial gene essentiality

Advances and perspectives in computational prediction of microbial gene essentiality

Brief Funct Genomics. 2016 Feb 8. pii: elv063. 

Fredrick M Mobegi, Aldert Zomer, Marien I de Jonge, Sacha AFT van Hijum

The minimal subset of genes required for cellular growth, survival and viability of an organism are classified as essential genes. Knowledge of essential genes gives insight into the core structure and functioning of a cell. This might lead to more efficient antimicrobial drug discovery, to elucidation of the correlations between genotype and phenotype, and a better understanding of the minimal requirements for a (synthetic) cell. Traditionally, constructing a catalog of essential genes for a given microbe involved costly and time-consuming laboratory experiments. While experimental methods have produced abundant gene essentiality data for model organisms like Escherichia coli and Bacillus subtilis, the knowledge generated cannot automatically be extrapolated to predict essential genes in all bacteria. In addition, essential genes identified in the laboratory are by definition 'conditionally essential', as they are essential under the specified experimental conditions: these might not resemble conditions in the microorganisms' natural habitat(s). Also, large-scale experimental assaying for essential genes is not always feasible because of the time investment required to setup these assays. The ability to rapidly and precisely identify essential genes in silico is therefore important and has great potential for applications in medicine, biotechnology and basic biological research. Here, we review the advances made in the use of computational methods to predict microbial gene essentiality, perspectives for the future of these techniques and the possible practical applications of essential genes.

Campylobacter fetus Subspecies Contain Conserved Type IV Secretion Systems on Multiple Genomic Islands and Plasmids

Campylobacter fetus Subspecies Contain Conserved Type IV Secretion Systems on Multiple Genomic Islands and Plasmids

PLoS One. 2016 Apr 6;11(4):e0152832. doi: 10.1371/journal.pone.0152832. eCollection 2016.

Linda van der Graaf–van Bloois, William G Miller, Emma Yee, Gregor Gorkiewicz, Ken J Forbes, Aldert L Zomer, Jaap A Wagenaar, Birgitta Duim

The features contributing to differences in pathogenicity of the Campylobacter fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode a type IV secretion system (T4SS) and fic domain (filamentation induced by cyclic AMP) proteins, which may disrupt host cell processes. In the genomes of 27 C. fetus strains, three phylogenetically-different T4SS-encoding regions (T4SSs) were identified: one was located in both the chromosome and in extra-chromosomal plasmids; one was located exclusively in the chromosome; and one exclusively in extra-chromosomal plasmids. We observed that C. fetus strains can contain multiple T4SSs and that homologous T4SSs can be present both in chromosomal genomic islands (GI) and on plasmids in the C. fetus strains. The GIs of the chromosomally located T4SS differed mainly by the presence of fic genes, insertion sequence elements and phage-related or hypothetical proteins. Comparative analysis showed that T4SS sequences, inserted in the same locations, were conserved in the studied C. fetus genomes. Using phylogenetic analysis of the T4SSs, it was shown that C. fetus may have acquired the T4SS regions from other Campylobacter species by horizontal gene transfer. The identified T4SSs and fic genes were found in Cff and Cfv strains, although the presence of T4SSs and fic genes were significantly associated with Cfv strains. The T4SSs and fic genes could not be associated with S-layer serotypes or geographical origin of the strains.

Comparative genomics and functional analysis of the 936 group of lactococcal Siphoviridae phages

Comparative genomics and functional analysis of the 936 group of lactococcal Siphoviridae phages

Sci Rep. 2016 Feb 19;6:21345. doi: 10.1038/srep21345.

James Murphy, Francesca Bottacini, Jennifer Mahony, Philip Kelleher, Horst Neve, Aldert Zomer, Arjen Nauta, Douwe van Sinderen

Genome sequencing and comparative analysis of bacteriophage collections has greatly enhanced our understanding regarding their prevalence, phage-host interactions as well as the overall biodiversity of their genomes. This knowledge is very relevant to phages infecting Lactococcus lactis, since they constitute a significant risk factor for dairy fermentations. Of the eighty four lactococcal phage genomes currently available, fifty five belong to the so-called 936 group, the most prevalent of the ten currently recognized lactococcal phage groups. Here, we report the genetic characteristics of a new collection of 936 group phages. By combining these genomes to those sequenced previously we determined the core and variable elements of the 936 genome. Genomic variation occurs across the 936 phage genome, such as genetic elements that (i) lead to a +1 translational frameshift resulting in the formation of additional structures on the phage tail, (ii) specify a double neck passage structure, and (iii) encode packaging module-associated methylases. Hierarchical clustering of the gene complement of the 936 group phages and nucleotide alignments allowed grouping of the ninety 936 group phages into distinct clusters, which in general appear to correspond with their geographical origin.

Joomla templates by a4joomla