Anti-adhesion methods as novel therapeutics for bacterial infections

Cozens, Daniel; Read, Robert C.

doi:10.1586/eri.12.145

Cited by 87 publications

(71 citation statements)

References 103 publications

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“…Targeting bacterial adhesion to solid surfaces is a promising approach to prevent biofilm-related disease [1][2][3]. This particularly holds true for the oral cavity where the long-standing presence of biofilms on teeth is the main cause of dental caries and periodontitis [4,5].…”

Section: Introductionmentioning

confidence: 99%

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

Kristensen

Zeng

Neu

et al. 2017

Journal of Oral Microbiology

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The bovine milk protein osteopontin (OPN) may be an efficient means to prevent bacterial adhesion to dental tissues and control biofilm formation. This study sought to determine to what extent OPN impacts adhesion forces and surface attachment of different bacterial strains involved in dental caries or medical device-related infections. It further investigated if OPN's effect on adhesion is caused by blocking the accessibility of glycoconjugates on bacterial surfaces. Bacterial adhesion was determined in a shear-controlled flow cell system in the presence of different concentrations of OPN, and interaction forces of single bacteria were quantified using single-cell force spectroscopy before and after OPN exposure. Moreover, the study investigated OPN's effect on the accessibility of cell surface glycoconjugates through fluorescence lectin-binding analysis. OPN strongly affected bacterial adhesion in a dose-dependent manner for all investigated species (Actinomyces naeslundii, Actinomyces viscosus, Lactobacillus paracasei subsp. paracasei, Staphylococcus epidermidis, Streptococcus mitis, and Streptococcus oralis). Likewise, adhesion forces decreased after OPN treatment. No effect of OPN on the lectin-accessibility to glycoconjugates was found. OPN reduces the adhesion and adhesion force/energy of a variety of bacteria and has a potential therapeutic use for biofilm control. OPN acts upon bacterial adhesion without blocking cell surface glycoconjugates. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

Kristensen

Zeng

Neu

et al. 2017

Journal of Oral Microbiology

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“…Biofilm inhibitors, where bacteria are prevented from forming biofilms rather than being killed, are an alternative to antibiotics (11,12). An exciting approach is to competitively block intercellular adhesion, for example with antibodies or peptides that bind to CWA proteins and prevent homophilic interactions.…”

mentioning

confidence: 99%

Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Feuillie

Formosa-Dague

Hays

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus forms biofilms on indwelling medical devices using a variety of cell-surface proteins. There is growing evidence that specific homophilic interactions between these proteins represent an important mechanism of cell accumulation during biofilm formation, but the underlying molecular mechanisms are still not well-understood. Here we report the direct measurement of homophilic binding forces by the serine-aspartate repeat protein SdrC and their inhibition by a peptide. Using single-cell and single-molecule force measurements, we find that SdrC is engaged in low-affinity homophilic bonds that promote cell-cell adhesion. Low-affinity intercellular adhesion may play a role in favoring biofilm dynamics. We show that SdrC also mediates strong cellular interactions with hydrophobic surfaces, which are likely to be involved in the initial attachment to biomaterials, the first stage of biofilm formation. Furthermore, we demonstrate that a peptide derived from β-neurexin is a powerful competitive inhibitor capable of efficiently blocking surface attachment, homophilic adhesion, and biofilm accumulation. Molecular modeling suggests that this blocking activity may originate from binding of the peptide to a sequence of SdrC involved in homophilic interactions. Our study opens up avenues for understanding the role of homophilic interactions in staphylococcal adhesion, and for the design of new molecules to prevent biofilm formation during infection.Staphylococcus aureus | SdrC | adhesion | biofilms | inhibition T he nosocomial pathogen Staphylococcus aureus is a major cause of superficial and invasive infections. A remarkable trait of this bacterium is its ability to form biofilms on implanted devices, thereby triggering infections that are difficult to treat with antibiotics (1, 2). Biofilm formation is initiated by attachment of the bacteria to abiotic surfaces, protein-coated materials, and host cells, and followed by cell-cell adhesion and multiplication leading to a mature biofilm (1, 2). A variety of cell-surface components are involved in intercellular interactions (2, 3). Although the polycationic polysaccharide intercellular adhesin has long been thought to be the main component promoting intercellular adhesion (4, 5), there is now a compelling body of evidence that cell wall-anchored (CWA) proteins are also involved (2, 3). Several recombinant CWA proteins have been shown to form dimers in solution (6-9). In some cases (i.e., Aap), crystallographic studies have provided insights into the mechanism of dimer formation (9, 10). Although very useful, in vitro methods provide information on purified molecules that are removed from their cellular context. Clearly, elucidating the molecular mechanisms by which CWA proteins self-associate in vivo is key to enhancing our understanding of biofilm accumulation.The increase of multidrug-resistant strains has created an urgent need for new therapeutics for bacterial infections. Biofilm inhibitors, where bacteria are prevented from forming biofilms rather than...

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“…In this situation, large quantities of foreign protein molecules are required, increasing the chance of immunogenic or toxic effect. Development of appropriate methods to deliver adhesin analogs close to the site of infection is also challenging [18]. Receptor analogs (glycomimetics, adhesin inhibitors) provide overall reduction of available active sites by 'filling out' adhesins expressed on host cells ( Figure 2B).…”

Section: Carbohydrate-lectin Interactionsmentioning

confidence: 99%

“…Receptor analogs (glycomimetics, adhesin inhibitors) provide overall reduction of available active sites by 'filling out' adhesins expressed on host cells ( Figure 2B). The use of a cocktail of inhibitors directed towards different carbohydrate specificities has a key advantage of targeting multiple adhesins at the same time [18]. Due to the similarity of the glycans to the structures present on the host cells, they rarely cause immunogenicity or toxicity, even when delivered in excess.…”

Section: Carbohydrate-lectin Interactionsmentioning

confidence: 99%

“…Furthermore, glycan receptors can be placed in a large number on different scaffolds (multivalent systems) or expressed by bacterial species derived from natural flora of the body and provided as probiotics ( Figure 2C) [19]. Production of antibodies against glycans present on pathogenic agents is a common approach when surface proteins are heavily glycosylated and cover the peptide part which cannot be reached by antibodies ( Figure 2D) [18]. …”

Section: Carbohydrate-lectin Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Utratna¹,

Deegan²,

Joshi³

2016

J Bioterror Biodef

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Pathogen adherence to a host cell is one of the first essential steps for establishing invasion, colonization and release of virulence factors such as toxins. Understanding the mechanisms used by pathogens and toxins to adhere and invade human cells could lead to the development of new strategies for preventing and controlling the spread of infectious diseases. This review focuses on carbohydrate-lectin interactions utilized by selected biothreat agents to bind and invade host cells. The principle of using anti-adhesion molecules, based on glycobiology research, has already been shown to be effective in the treatment of influenza. Therefore, translating the same principle to other biothreat agents that mediate invasion of a host cell through carbohydrate-lectin mechanisms is a very promising strategy. We investigate recent literature to highlight the latest developments in the field of glycobiology focused on inhibiting the initial steps of pathogen invasion, with examples for bacteria, toxin and virus interactions. The successful glycomimetics and glycoconjugates represent strategies for interruption of adhesion by single molecules and in multivalent systems against uropathogenic E. coli, several toxins (Shiga-like, cholera, botulinum) and wellknown or emerging viruses (influenza, HIV, Ebola, and Zika). This review provides promising directions and prophylactic as well as therapeutic potential of anti-adhesive strategies against selected biothreat targets.

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Anti-adhesion methods as novel therapeutics for bacterial infections

Cited by 87 publications

References 103 publications

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

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