Hans SteenackersKU Leuven | ku leuven · Department of Microbial and Molecular Systems (M²S)
Hans Steenackers
PhD
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66
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Publications (66)
The rapid increase of antibiotic-resistant pathogens is severely limiting our current treatment possibilities. An important subset of the resistance mechanisms conferring antibiotic resistance have public effects, allowing otherwise susceptible bacteria to also survive antibiotic treatment. As susceptible bacteria can survive treatment without bear...
Bacteria typically live in dense communities where they are surrounded by other species and compete for a limited amount of resources. These competitive interactions can induce defensive responses that also protect against antimicrobials, potentially complicating the antimicrobial treatment of pathogens residing in polymicrobial consortia. Therefor...
Biofilms contain extracellular polymeric substances (EPS) that provide structural support and restrict penetration of antimicrobial treatment. To overcome limited penetration, functionalized nanoparticles (NPs) have been suggested as carriers for antimicrobial delivery. Using microscopy, we evaluate the diffusion of nanoparticles in function of the...
Background
Tannins have demonstrated antibacterial and antibiofilm activity, but there are still unknown aspects on how the chemical properties of tannins affect their biological properties. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and an...
Bacteria are social organisms that commonly live in dense communities surrounded by a multitude of other species. The competitive and cooperative interactions between these species not only shape the bacterial communities but also influence their susceptibility to antimicrobials. While several studies have shown that mixed-species communities are m...
Biomolecule immobilization onto implant surfaces is an interesting approach which allows fine-tuning the biological response upon implantation. However, the relatively low adsorption rates seen in current methodologies typically lead to long processing times, which can affect the activity of the biomolecules. Here, we investigate the effect of comb...
In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and k...
Extracellular polymeric substances (EPS) in bacterial biofilms complicate treatment by inactivating drugs and slowing down diffusion. Through enhanced penetration and resistance to degradation in bacterial biofilms, nanoparticle (NP) carriers can help improve biofilm treatment. However, the way in which biofilm architecture influences the diffusive...
In Saccharomyces cerevisiae , the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, resulting in enrichment of cooperators within the flocs. Given this dual function in...
Objective
Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order...
Objective
Vascular graft infection (VGI) is a serious complication with a high mortality and morbidity rate. Several measures could be taken to reduce the risk. One of them are silver containing vascular grafts. However, to date, no clinical advantages have been reported. This study reviews the outcome of preclinical studies focusing on the role of...
Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need...
Cleaning and disinfection protocols are not always able to remove biofilm microbes present in breweries, indicating that novel anti-biofilm strategies are needed. The preventive activities of three in-house synthesized members of the 2-aminoimidazole class of anti-biofilm molecules were studied against 17 natural brewery biofilms and benchmarked ag...
Salmonella biofilms are a common cause of contaminations in the food or feed industry. In a screening for novel compounds to combat biofilm-associated foodborne outbreaks, we identified agaric acid as a Salmonella Typhimurium biofilm inhibitor that does not affect planktonic growth. Importantly, the remaining biofilm cells after preventive treatmen...
Bacteria use complex regulatory networks to cope with stress, but the function of these networks in natural habitats is poorly understood. The competition sensing hypothesis states that bacterial stress response systems can serve to detect ecological competition, but studying regulatory responses in diverse communities is challenging. Here, we solv...
Bacteria commonly form dense biofilms encased in extracellular polymeric substances (EPS). Biofilms are often extremely tolerant to antimicrobials but their reliance on shared EPS may also be a weakness as social evolution theory predicts that inhibiting shared traits can select against resistance. Here we show that EPS of Salmonella biofilms is a...
Biofilms, especially those formed by Staphylococcus aureus, play a key role in the development of orthopedic implant infections. Eradication of these infections is challenging due to the elevated tolerance of biofilm cells against antimicrobial agents. In this study, we developed an antibiofilm coating consisting of 5‐(4‐bromophenyl)‐N‐cyclopentyl‐...
Genetic diversity often enhances the tolerance of microbial communities against antimicrobial treatment. However the sociobiology underlying this antimicrobial tolerance remains largely unexplored. Here we analyze how inter-species interactions can increase antimicrobial tolerance. We apply our approach to 17 industrially relevant multispecies biof...
Microbial biofilm contamination is an ubiquitous and persistent problem in industry and clinics. The structure of the biofilm, its extracellular matrix and its formation process are very complex. At present, there are only limited options to investigate biofilms outside the lab, as most in situ techniques lack sensitivity and resolution. Impedance-...
The response regulator PhoP, which is part of the PhoP/PhoQ two-component system, regulates the expression of multiple genes involved in controlling virulence in Salmonella enterica serovar Typhimurium and other species of Gram-negative bacteria. Modulating the phosphorylation-mediated dimerization in the receiver domain may interfere with the tran...
The ASM Conference on Mechanisms of Interbacterial Cooperation and Competition was held in Washington DC, from 1 to 4 March 2017. The conference provided an international forum for sociomicrobiologists from different disciplines to present and discuss new findings. The meeting covered a wide range of topics, spanning molecular mechanisms, ecology,...
Genetic diversity often enhances the tolerance of microbial communities against antimicrobial treatment. However the sociobiology underlying this antimicrobial tolerance remains largely unexplored. Here we analyze how inter-species interactions can increase antimicrobial tolerance. We apply our approach to 17 industrially-relevant multispecies biof...
Probiotic Lactobacillus strains are widely used to benefit human and animal health, although the exact mechanisms behind their interactions with the host and the microbiota are largely unknown. Fluorescent tagging of live probiotic cells is an important tool to unravel their modes of action. In this study, the implementation of different heterologo...
Table S1. Primers used in this study.
Fig. S1. Map of pMEC45 carrying gfp (green arrow) and pMEC45‐derived plasmids carrying mTagBFP2 (dark blue arrow, in pCMPG11260), mCherry (red arrow, in pCMPG11261), mVenus (yellow arrow, in pCMPG11262) or ecfp (cyan arrow, in pCMPG11263) under the control of the L. lactis inducible nisA promoter (PnisA, black arrow). The plasmids contain the L. la...
The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing...
Most of the human bacterial infections are associated with the biofilm formation and the natural tolerance of biofilms to antibiotics challenges treatment. Because of their low immunity, cancer patients are especially susceptible to bacterial infections. Compounds with anti-biofilm activity could therefore become a useful adjunct to chemotherapy, i...
There is an urgent need for new antibacterial drugs that are robust against the development of resistance. Drug repurposing is a cost-effective strategy to fast-track the drug development process. Here we examine why the nucleoside and nucleobase analogue drugs in particular present an attractive class for repurposing. Some of these drugs have alre...
Metal-organic frameworks (MOFs) have a large potential for delivery of active molecules. Here, a MOF coating is investigated as a smart host matrix for triggered release of anti-biofilm compounds. Besides a coating consisting of the regular Fe-terephthalate MIL-88B(Fe), a new hydrophobic MIL-88B(Fe) coating is synthesized in hydrothermal conditions...
Previously, we have synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that show a preventive activity against biofilm formation of Salmonella Typhimurium and Pseudomonas aeruginosa Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted compounds against a broad pane...
Biofilm formation is an important survival strategy of Salmonella in all environments. By mutant screening, we showed a knock-out mutant of fabR, encoding a repressor of unsaturated fatty acid biosynthesis (UFA), to have impaired biofilm formation. In order to unravel how this regulator impinges on Salmonella biofilm formation, we aimed at elucidat...
Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031,...
Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of...
During the last decade it has been shown that among cell variation in gene expression plays an important role within clonal populations. Here, we provide an overview of the different mechanisms contributing to gene expression variability in clonal populations. These are ranging from inherent variations in the biochemical process of gene expression...
Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low...
We report the design, synthesis and antibacterial activity analysis of conjugates of vancomycin and cathelicidin-related antimicrobial peptides (CRAMP). Vancomycin inhibits the nascent peptidoglycan synthesis and is highly active against Gram-positive bacteria, whereas Gram-negative bacteria are generally insensitive due to a protective outer membr...
Post-transcriptional regulation is a very important mechanism to control gene expression in changing environments. In the past decade, a lot of interest has been directed toward the role of small RNAs (sRNAs) in bacterial post-transcriptional regulation. However, sRNAs are not the only molecules controlling gene expression at this level, RNA-bindin...
Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and H...
We identified a 26-amino-acid truncated form of the 34-amino-acid cathelicidin-related antimicrobial peptide (CRAMP) in the
islets of Langerhans of the murine pancreas. This peptide, P318, shares 67% identity with the LL-37 human antimicrobial peptide.
As LL-37 displays antimicrobial and antibiofilm activity, we tested antifungal and antibiofilm ac...
A microwave-assisted protocol was developed for the construction of 2-amino-1H-imidazole/triazole conjugates starting from the previously described 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts. The process involves a one-pot hydrazinolysis/Dimroth-rearrangement of these salts followed by a ligand-free copper nanoparticle-catalyzed a...
Salmonella, an important foodborne pathogen, forms biofilms in many different environments. The composition of these biofilms differs depending on the growth conditions, and their development is highly coordinated in time. To develop efficient treatments, it is therefore essential that biofilm formation and its inhibition be understood in different...
Nowadays, the identification of small non-coding RNAs takes a prominent role in deciphering complex bacterial phenotypes. Evidences are given that the post-transcriptional layer of regulation mediated by sRNAs plays an important role in the formation of bacterial biofilms. These sRNAs exert their activity on various targets, be it directly or indir...
A screening of a small-molecule library was conducted, in search of Salmonella biofilm inhibitors active in a broad temperature range, both in prevention and in eradication of biofilms. Moreover, the inhibitors were selected not to influence the planktonic growth of Salmonella to diminish the selective pressure and to prevent or slow down resistanc...
The ability of Salmonella to form complex surface-associated communities, called biofilms, contributes to its resistance and persistence in both host and non-host environments and is especially important in food processing environments. In this review, the different types of abiotic (plastic, glass, cement, rubber, and stainless steel) and biotic s...
A library of 80 1-substituted 2-hydroxy-2-aryl-2,3-dihydro-imidazo[1,2-a]pyrimidinium salts and 54 2N-substituted 4(5)-aryl-2-amino-1H-imidazoles was synthesized and tested for the antagonistic effect against biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa. The nature of the substituent at the 1-position of the salts was foun...
Diverse iminoimidazolines (III) are synthesized from readily available polysubstituted propargylamines and thioureas in a one-pot process using an Ag(I) catalyst.
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Significance
Reported is the silver-mediated synthesis of 1,4,5-trisubstituted 2-aminoimidazoles 4 starting from secondary propargylamines 1 and thioureas 2. Silver nitrate in acetonitrile was found to be the most efficient catalyst. The guanylation and the cyclization steps can be carried out either in a step...
A library of 112 4(5)-aryl-2-amino-1H-imidazoles, 4,5-diphenyl-2-amino-1H-imidazoles, and N1-substituted 4(5)-phenyl-2-aminoimidazoles was synthesized and tested for the antagonistic effect against biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa. The substitution pattern of the 4(5)-phenyl group and the nature of the N1-subst...
A library of 25 1'-unsubstituted and 1'-bromo or 1'-acetoxy 3-alkyl-5-methylene-2(5H)-furanones and two 3-alkylmaleic anhydrides was synthesized using existing and new methods. This library was tested for the antagonistic effect against the biofilm formation by Salmonella Typhimurium and the quorum sensing regulated bioluminescence of Vibrio harvey...
Salmonella enterica serovar Typhimurium is a main cause of bacterial food-borne diseases. As Salmonella can form biofilms in which it is better protected against antimicrobial agents on a wide diversity of surfaces, it is of
interest to explore ways to inhibit biofilm formation. Brominated furanones, originally extracted from the marine alga Delise...