Bacterial clustering biomaterials as anti-infective therapies.

In Nature, bacterial clustering by host-released peptides or nucleic acids is an evolutionarily conserved immune defense strategy employed to prevent adhesion of pathogenic microbes, which is prerequisite for most infections. Synthetic anti-adhesion strategies present as non-lethal means of targeting bacteria and may potentially be used to avoid resistance against antimicrobial therapies. From bacteria-agglutinating biomolecules discovered in nature to synthetic designs involving peptides, cationic polymers and nanoparticles, the modes of actions appear broad and unconsolidated.

Structure-Guided Bacteria Specificity and Wide Activity Spectrum of Endotoxin-Responsive Peptide Nanonets.

Peptide nanonets offer a promising avenue for constructing anti-infective biomaterials. Our group recently reported innovative designs of synthetic BTT nanonets that fibrillate selectively in response to bacterial endotoxins. Herein, we delved deeper into the molecular interactions between our peptides and these bacteria-specific biomolecules, which is an aspect critically missing from major works in the field.

Stapled β-Hairpin Antimicrobial Peptides with Improved Stability and Activity against Drug-Resistant Gram-Negative Bacteria.

Different stapling techniques have been used recently to address the subpar performance of antimicrobial peptides (AMPs) in clinical trials with ample focus on α-helical AMPs. In comparison, a systematic evaluation of such strategies on β-hairpin AMPs is lacking. Herein, we report the design, synthesis, and evaluation of a library of all-hydrocarbon-stapled β-hairpin AMPs with variation in key parameters intended as potent therapeutics against drug-resistant pathogens.

Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro-Inflammatory Cytokines.

Extracellular lipopolysaccharide (LPS) released from bacteria cells can enter the bloodstream and cause septic complications with excessive host inflammatory responses. Target-specific strategies to inactivate inflammation mediators have largely failed to improve the prognosis of septic patients in clinical trials. By utilizing their high density of positive charges, de novo designed peptide nanonets are shown to selectively entrap the negatively charged LPS and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Sugar-Assisted Cryopreservation of Stem Cell-Laden Gellan Gum-Collagen Interpenetrating Network Hydrogels.

Tissue engineering involves the transplantation of stem cell-laden hydrogels as synthetic constructs to replace damaged tissues. However, their time-consuming fabrication procedures are hurdles to widespread application in clinics. Fortunately, similar to cell banking, synthetic tissues could be cryopreserved for subsequent central distribution.

Novel tetrameric cell penetrating antimicrobial peptoids effective against mycobacteria and drug-resistant .

Background: Antimicrobial peptides (AMPs) are short, cationic, amphipathic molecules that have gained tremendous popularity as alternatives to traditional antibiotics due to their lower propensity to develop bacterial resistance. However, the clinical developability of AMPs remains impeded due to shortcomings such as proteolytic instability and poor penetration leading to low bioavailability.

Aims: To improve the access of AMPs to cells and subsequent bacteria killing, we evaluated the cell-penetrating and antimicrobial properties of three novel libraries of synthetic peptoids using Minimum Inhibitory Concentration, killing efficacy and membrane permeabilization assays against mycobacteria and .

Rationalisation of Antifungal Properties of α-Helical Pore-Forming Peptide, Mastoparan B.

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including , , , and .

Pristine Gellan Gum-Collagen Interpenetrating Network Hydrogels as Mechanically Enhanced Anti-inflammatory Biologic Wound Dressings for Burn Wound Therapy.

Gellan gum is a biologically inert natural polymer that is increasingly favored as a material-of-choice to form biorelevant hydrogels. However, as a burn wound dressing, native gellan gum hydrogels do not drive host's biology toward regeneration and are mechanically inadequate wound barriers. To overcome these issues, we fabricateda gellan gum-collagen full interpenetrating network (full-IPN) hydrogel that can house adipose-derived mesenchymal stem cells (ADSCs) and employ their multilineage differentiation potential and produce wound-healing paracrine factors to reduce inflammation and promote burn wound regeneration.

Wirelessly operated bioelectronic sutures for the monitoring of deep surgical wounds.

Monitoring surgical wounds post-operatively is necessary to prevent infection, dehiscence and other complications. However, the monitoring of deep surgical sites is typically limited to indirect observations or to costly radiological investigations that often fail to detect complications before they become severe. Bioelectronic sensors could provide accurate and continuous monitoring from within the body, but the form factors of existing devices are not amenable to integration with sensitive wound tissues and to wireless data transmission.

Manipulating turn residues on de novo designed β-hairpin peptides for selectivity against drug-resistant bacteria.

Synthetic β-hairpin antimicrobial peptides (AMPs) offer a useful source for the development of novel antimicrobial agents. β-hairpin peptides generally consist of two side strands bridged by a reverse turn. In literature, most studies focused on the modifications of the side strands to manipulate the stability and activity of β-hairpin peptides, and much less is known about the impact of the turn region.

Extract as a Serum Replacement That Enhances Mammalian Cell Growth and Protein Expression.

The global cell culture market is experiencing significant growth due to the rapid advancement in antibody-based and cell-based therapies. Both rely on the capacity of different living factories, namely prokaryotic and eukaryotic cells, plants or animals for reliable and mass production. The ability to improve production yield is of important concern.

Nucleic acid peptide nanogels for the treatment of bacterial keratitis.

Cage-shaped nucleic acid nanocarriers are promising molecular scaffolds for the organization of polypeptides. However, there is an unmet need for facile loading strategies that truly emulate nature's host-guest systems to drive encapsulation of antimicrobial peptides (AMPs) without loss of biological activity. Herein, we develop DNA nanogels with rapid in situ loading of L12 peptide during the thermal annealing process.

Silica Nanoparticles-A Versatile Tool for the Treatment of Bacterial Infections.

The rapid emergence of drug resistance continues to outpace the development of new antibiotics in the treatment of infectious diseases. Conventional therapy is currently limited by drug access issues such as low intracellular drug accumulations, drug efflux by efflux pumps and/or enzymatic degradation. To improve access, targeted delivery using nanocarriers could provide the quantum leap in intracellular drug transport and retention.

Biomimicry of microbial polysaccharide hydrogels for tissue engineering and regenerative medicine - A review.

Hydrogels as artificial biomaterial scaffolds offer a much favoured 3D microenvironment for tissue engineering and regenerative medicine (TERM). Towards biomimicry of the native ECM, polysaccharides from Nature have been proposed as ideal surrogates given their biocompatibility. In particular, derivatives from microbial sources have emerged as economical and sustainable biomaterials due to their fast and high yielding production procedures.

Ultra-Short Antimicrobial Peptoids Show Propensity for Membrane Activity Against Multi-Drug Resistant .

Tuberculosis (TB) results in both morbidity and mortality on a global scale. With drug resistance on the increase, there is an urgent need to develop novel anti-mycobacterials. Thus, we assessed the anti-mycobacterial potency of three novel synthetic peptoids against drug-susceptible and multi-drug resistant (MDR) using Minimum Inhibitory Concentration, killing efficacy and intracellular growth inhibition assays, and against mycobacteria infected BALB/c mice.

Developing inhaled protein therapeutics for lung diseases.

Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This review examines the important considerations and challenges in designing an inhaled protein therapeutics for local lung delivery: the choice of inhalation device, structural changes affecting drug deposition in diseased lungs, clearance mechanisms affecting an inhaled protein drug's lung accumulation, protein stability, and immunogenicity.

Facile and efficient encapsulation of antimicrobial peptides via crosslinked DNA nanostructures and their application in wound therapy.

There is growing interest in the development of nucleic acid nanostructures as smart functional materials for applications in drug delivery. Inspired by the diverse physical interactions that exist in nature, crosslinked DNA nanostructures can serve as attractive affinity binding networks that interact with therapeutic cargos or living cells. Herein we report a strategy that addresses the challenges of topical oligopeptide therapy by exploiting high binding affinity between polyanionic DNA nanostructures and cationic antimicrobial peptides (AMPs) to fabricate hydrogels that release a model antimicrobial L12 peptide in response to pathogenic S.

Correction to: Candidemia in a major regional tertiary referral hospital - epidemiology, practice patterns and outcomes.

[This corrects the article DOI: 10.1186/s13756-017-0184-1.].

Integrated pharmacokinetic-pharmacodynamic modeling to evaluate empiric carbapenem therapy in bloodstream infections.

Objectives: Treatment for nosocomial bloodstream infections (BSI) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) is challenging. Rising antimicrobial resistance, especially in extended spectrum beta-lactamase production, inadvertently increases empiric carbapenem consumption. Three antipseudomonal carbapenems (imipenem, meropenem [MER], and doripenem [DOR]) are available commercially against MDR GNB in Singapore.

Antimicrobial and Anti-Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity.

Protein-based polymeric polyelectrolytes are emerging as alternative synthetic nanoparticles owing to their biodegradability and biocompatibility. However, potential in vivo toxicity remains a significant challenge. Herein an array of protein polyelectrolytes generated from cationic human serum albumin (cHSA) and polyethylene glycol (PEG) are synthesized via synthetic customization as antimicrobials for the treatment of systemic infections.

Rapid Antibiotic Combination Testing for Carbapenem-Resistant Gram-Negative Bacteria within Six Hours Using ATP Bioluminescence.

To guide the timely selection of antibiotic combinations against carbapenem-resistant Gram-negative bacteria (CR-GNB), an test with a short turnaround time is essential. We developed an ATP bioluminescence assay to determine effective antibiotic combinations against CR-GNB within 6 h. We tested 42 clinical CR-GNB strains (14 , 14 , and 14 strains) against 74 single antibiotics and two-antibiotic combinations.

Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds.

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH.

Macromolecular Conjugate and Biological Carrier Approaches for the Targeted Delivery of Antibiotics.

For the past few decades, the rapid rise of antibiotic multidrug-resistance has presented a palpable threat to human health worldwide. Meanwhile, the number of novel antibiotics released to the market has been steadily declining. Therefore, it is imperative that we utilize innovative approaches for the development of antimicrobial therapies.

Disruption of drug-resistant biofilms using de novo designed short α-helical antimicrobial peptides with idealized facial amphiphilicity.

Unlabelled: The escalating threat of antimicrobial resistance has increased pressure to develop novel therapeutic strategies to tackle drug-resistant infections. Antimicrobial peptides have emerged as a promising class of therapeutics for various systemic and topical clinical applications. In this study, the de novo design of α-helical peptides with idealized facial amphiphilicities, based on an understanding of the pertinent features of protein secondary structures, is presented.