Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids.

Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains (, , , and ), pathogenic fungi (, , and ), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity.

FabR, a regulator of membrane lipid homeostasis, is involved in biofilm robustness.

Biofilm is a dynamic structure from which individual bacteria and micro-aggregates are released to subsequently colonize new niches by either detachment or dispersal. Screening of a transposon mutant library identified genes associated with the alteration of biofilm including , which encodes a transcriptional regulator involved in membrane lipid homeostasis. An isogenic ∆ mutant formed more biofilm than the wild-type (WT) strain and its trans-complemented strain.

Novel Honeycomb Nanoclay Frameworks With Hemostatic and Antibacterial Properties.

Our laboratory recently developed a new class of high surface area, honeycomb Nanoclay Microsphere Framework absorbents (NMFs) that prompt rapid hemostasis. In the present work, we propose a novel approach to develop antibacterial Topical Hemostatic Agents (THAs) by anchoring silver nanoparticles (AgNPs) onto NMFs. This combination was obtained by a chemical co-reduction approach, followed by freeze-processing, and was shown to ensure stability and on-site delivery of AgNPs, without altering the hemostatic properties of NMFs.

Design of Triazolium-Grafted Peptidomimetic Macrocycles with Facial Amphipathicity to Target Pathogenic Bacteria.

Access to 1,2,3-triazolium-grafted peptoid macrocycles was developed by macrocyclization and multivalent postmodification of linear peptoid oligomers carrying an alternance of benzylic and propargyl groups as side chains. X-ray analysis and NMR studies revealed a conformational preference for constrained hairpin-shaped structures leading to the facial amphipathic character of these macrocycles. A preliminary evaluation showed the antimicrobial activities of these new cationic amphipathic architectures.

Elemental sulfur enhances the anti-fungal effect of Lacticaseibacillus rhamnosus Lcr35.

Lacticaseibacillus rhamnosus Lcr35 is a well-known bacterial strain whose efficiency in preventing recurrent vulvovaginal candidiasis has been largely demonstrated in clinical trials. The presence of sodium thiosulfate (STS) has been shown to enhance its ability to inhibit the growth of Candida albicans strains. In this study, we confirmed that Lcr35 has a fungicidal effect not only on the planktonic form of C.

Role of Klebsiella pneumoniae Type VI secretion system (T6SS) in long-term gastrointestinal colonization.

Type VI secretion systems (T6SS), recently described in hypervirulent K. pneumoniae (hvKp) strains, are involved in bacterial warfare but their role in classical clinical strains (cKp) has been little investigated. In silico analysis indicated the presence of T6SS clusters (from zero to four), irrespective of the strains origin or virulence, with a high prevalence in the K.

Lacticaseibacillus rhamnosus Lcr35 Stimulates Epithelial Vaginal Defenses upon Gardnerella vaginalis Infection.

Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria, such as Gardnerella vaginalis, and low levels of "healthy" lactobacilli leads to bacterial vaginosis (BV), usually associated with a low-grade inflammatory process. Despite appropriate antibiotic treatment, -associated BV is characterized by significant recurrence. The use of probiotics could be an interesting alternative therapy due to their ability to rebalance vaginal microbiota.

Plasmidome analysis of a hospital effluent biofilm: Status of antibiotic resistance.

Plasmids are widely involved in the dissemination of characteristics within bacterial communities. Their genomic content can be assessed by high-throughput sequencing of the whole plasmid fraction of an environment, the plasmidome. In this study, we analyzed the plasmidome of a biofilm formed in the effluents of the teaching hospital of Clermont-Ferrand (France).

Tailored therapeutic release from polycaprolactone-silica hybrids for the treatment of osteomyelitis: antibiotic rifampicin and osteogenic silicates.

The treatment of osteomyelitis, a destructive inflammatory process caused by bacterial infections to bone tissue, is one of the most critical challenges of orthopedics and bone regenerative medicine. The standard treatment consists of intense antibiotic therapies combined with tissue surgical debridement and the application of a bone defect filler material. Unfortunately, commercially available candidates, such as gentamicin-impregnated polymethylmethacrylate cements, possess very poor pharmacokinetics (, 24 hours burst release) and little to no regenerative potential.

Tick ecology and Lyme borreliosis prevention: a regional survey of pharmacists' knowledge in Auvergne-Rhône-Alpes, France.

The most prevalent vector-borne diseases in Europe are caused by tick-borne pathogens, such as bacteria of the genus Borrelia that cause Lyme borreliosis. In this context, retail pharmacists are frequently the first medical source of information in the event of a tick bite. The objective of this study was to assess pharmacy professionals' knowledge about both tick ecology and the appropriate measures for tick bites and Lyme borreliosis prevention.

Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties.

Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates ( = 0.0, 0.

A prospective study on the pathogenesis of catheter-associated bacteriuria in critically ill patients.

Background: Updating the pathogenesis of catheter-associated bacteriuria (CA-bacteriuria) in the intensive care unit (ICU) is needed to adapt prevention strategies. Our aim was to determine whether the main pathway of CA-bacteriuria in ICU patients was endoluminal or exoluminal. In a prospective study, quantitative urine cultures were sampled from catheter sampling sites, collector bags and the catheter outer surface near the meatus from days 1 to 15 after catheterization.

Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35.

GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35. In this study, the LBP formulation and manufacturing process significantly enhanced the anti-Candida activity of L. rhamnosus Lcr35, with a complete loss of viability of the yeast after 48 h of coincubation.

Biological properties of copper-doped biomaterials for orthopedic applications: A review of antibacterial, angiogenic and osteogenic aspects.

Copper is an essential trace element required for human life, and is involved in several physiological mechanisms. Today researchers have found and confirmed that Cu has biological properties which are particularly useful for orthopedic biomaterials applications such as implant coatings or biodegradable filler bone substitutes. Indeed, Cu exhibits antibacterial functions, provides angiogenic ability and favors osteogenesis; these represent major key points for ideal biomaterial integration and the healing process that follows.

Antibiotic resilience: a necessary concept to complement antibiotic resistance?

Resilience is the capacity of systems to recover their initial state or functions after a disturbance. The concepts of resilience and resistance are complementary in ecology and both represent different aspects of the stability of ecosystems. However, antibiotic resilience is not used in clinical bacteriology whereas antibiotic resistance is a recognized major problem.

Fosfomycin and Staphylococcus aureus: transcriptomic approach to assess effect on biofilm, and fate of unattached cells.

Interest has been rekindled in the old antibiotic fosfomycin, partly because of its ability to penetrate biofilm. Using a transcriptomic approach, we investigated the modifications induced by fosfomycin in sessile cells of a clinical Staphylococcus aureus isolated from a device-associated infection. Cells still able to form biofilm after 4 h of incubation in the presence of subinhibitory concentrations of fosfomycin and cells from 24-h-old biofilm later submitted to fosfomycin had 6.

Colonization and immune modulation properties of biofilm-dispersed cells.

Biofilm-dispersal is a key determinant for further dissemination of biofilm-embedded bacteria. Recent evidence indicates that biofilm-dispersed bacteria have transcriptional features different from those of both biofilm and planktonic bacteria. In this study, the in vitro and in vivo phenotypic properties of cells spontaneously dispersed from biofilm were compared with those of planktonic and sessile cells.

Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae.

Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood, but cross talk between the intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defenses by modulating the intestinal microbiota with exogenous supplementation of beneficial strains.

Immobilisation of bacteria onto magnetic nanoparticles for the decolorisation and degradation of azo dyes.

Azo dyes are widely used in industries and their release in the environment contributes to the pollution of effluents. The authors aim to develop a new eco-friendly water treatment method for the degradation of azo dyes based on in situ magnetic separation and immobilisation of bacterial cells. The immobilisation was achieved using superparamagnetic FeO nanoparticles and offers the possibility of reusing bacteria by magnetic separation for several degradation cycles.

1,2,3-Triazolium-Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides.

Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus.

How do environment-dependent switching rates between susceptible and persister cells affect the dynamics of biofilms faced with antibiotics?

Persisters form sub-populations of stress-tolerant cells that play a major role in the capacity of biofilms to survive and recover from disturbances such as antibiotic treatments. The mechanisms of persistence are diverse and influenced by environmental conditions, and persister populations are more heterogeneous than formerly suspected. We used computational modeling to assess the impact of three switching strategies between susceptible and persister cells on the capacity of bacterial biofilms to grow, survive and recover from antibiotic treatments.

Unveiling and Characterizing Early Bilateral Interactions between Biofilm and the Mouse Innate Immune System.

A very substantial progress has been made in our understanding of infectious diseases caused by invasive bacteria. Under their planktonic forms, bacteria transiently reside in the otherwise sterile mammal body tissues, as the physiological inflammation insures both their clearance and repair of any tissue damage. Yet, the bacteria prone to experience planktonic to biofilm developmental transition still need to be studied.

Relating switching rates between normal and persister cells to substrate and antibiotic concentrations: a mathematical modelling approach supported by experiments.

We developed and compared two mathematical models of variable phenotypic switching rates between normal and persister cells that depend on substrate concentration and antibiotic presence. They could be used to simulate the formation of persisters in environments with concentration gradients such as biofilms. Our models are extensions of a previous model of the dynamics of normal and persistent cell populations developed by Balaban et al.

Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

Purpose: This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox).