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Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli , Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles. Biodegradable lignin nanoparticles infused with minimal amounts of silver ions and coated with a cationic polyelectrolyte show short-term broad-spectrum antimicrobial activity, offering an environmentally friendly alternative to metallic silver nanoparticles.

Background Carbapenem resistance is a critical healthcare challenge worldwide. Particularly concerning is the widespread dissemination of Klebsiella pneumoniae carbapenemase (KPC). Klebsiella pneumoniae harboring blaKPC (KPC-Kpn) is endemic in many areas including the United States, where the epidemic was primarily mediated by the clonal dissemination of Kpn ST258. We postulated that the spread of blaKPC in other regions occurs by different and more complex mechanisms. To test this, we investigated the evolution and dynamics of spread of KPC-Kpn in Colombia, where KPC became rapidly endemic after emerging in 2005. Methods We sequenced the genomes of 133 clinical isolates recovered from 24 tertiary care hospitals located in 10 cities throughout Colombia, between 2002 (before the emergence of KPC-Kpn) and 2014. Phylogenetic reconstructions and evolutionary mapping were performed to determine temporal and genetic associations between the isolates. Results Our results indicate that the start of the epidemic was driven by horizontal dissemination of mobile genetic elements carrying blaKPC-2, followed by the introduction and subsequent spread of clonal group 258 (CG258) isolates containing blaKPC-3. Conclusions The combination of 2 evolutionary mechanisms of KPC-Kpn within a challenged health system of a developing country created the “perfect storm” for sustained endemicity of these multidrug-resistant organisms in Colombia.

Background Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Methods C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. Results 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis , whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B , netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. Conclusions Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens . We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens . Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. Trial registration clinicaltrials.gov NCT01102738 , registered 13th April 2010.

Rapid discovery and development of serum-stable, selective, and high affinity peptide-based binders to protein targets are challenging. Angiotensin converting enzyme 2 (ACE2) has recently been identified as a cardiovascular disease biomarker and the primary receptor utilized by the severe acute respiratory syndrome coronavirus 2. In this study, we report the discovery of high affinity peptidomimetic binders to ACE2 via affinity selection-mass spectrometry (AS-MS). Multiple high affinity ACE2-binding peptides (ABP) were identified by selection from canonical and noncanonical peptidomimetic libraries containing 200 million members (dissociation constant, K D  = 19–123 nM). The most potent noncanonical ACE2 peptide binder, ABP N1 ( K D  = 19 nM), showed enhanced serum stability in comparison with the most potent canonical binder, ABP C7 ( K D  = 26 nM). Picomolar to low nanomolar ACE2 concentrations in human serum were detected selectively using ABP N1 in an enzyme-linked immunosorbent assay. The discovery of serum-stable noncanonical peptidomimetics like ABP N1 from a single-pass selection demonstrates the utility of advanced AS-MS for accelerated development of affinity reagents to protein targets. Angiotensin converting enzyme 2 (ACE2) has been identified as a cardiovascular disease biomarker and the primary receptor utilized by SARS-CoV-2, but developing serum-stable, selective and high-affinity binders for this target is challenging. Here, the authors use affinity selection-mass spectrometry to identify multiple high affinity ACE2-binding peptides from canonical and noncanonical peptidomimetic libraries containing 200 million members.

Cationic charge and hydrophobicity have long been understood to drive the potency and selectivity of antimicrobial peptides (AMPs). However, these properties alone struggle to guide broad success in vivo, where AMPs must differentiate bacterial and mammalian cells, while avoiding complex barriers. New parameters describing the biophysical processes of membrane disruption could provide new opportunities for antimicrobial optimization. In this work, we utilize oligothioetheramides (oligoTEAs) to explore the membrane-targeting mechanism of oligomers, which have the same cationic charge and hydrophobicity, yet show a unique ~ 10-fold difference in antibacterial potency. Solution-phase characterization reveals little difference in structure and dynamics. However, fluorescence microscopy of oligomer-treated Staphylococcus aureus mimetic membranes shows multimeric lipid aggregation that correlates with biological activity and helps establish a framework for the kinetic mechanism of action. Surface plasmon resonance supports the kinetic framework and supports lipid aggregation as a driver of antimicrobial function. Joseph Brown et al. use oligothioetheramides (oligo TEAs) to show that multimeric lipid aggregation in Staphylococcus aureus mimetic membranes correlates with the biological activity of oligoTEAs. These results may explain why antimicrobial peptides with identical cationic charge and hydrophobicity show different biological activity.

The involvement of women of childbearing potential in research has been discussed extensively in this journal and elsewhere. Various approaches have been proposed to deal with this tension, and each is subject to the criticism about the extent to which the balance is maintained. Here, Brown et al describe the outcome of an institutional review board's review process for a drug study in which even the most minimal of requirements for including female participants of childbearing potential was unacceptable to the commercial sponsor, leading to the sponsor's withdrawal of the study at the site. Presumably, the study is being conducted at other sites with no requirement that women of childbearing potential be included.

The use of contraception hi clinical research is often justified as a compromise between excluding women of childbearing potential completely from clinical trials with unclear fetal risk and including women who have the ability to become pregnant while taking an investigational agent. Here, Schonfeld et al investigate practices regarding pregnant women's eligibility to participate in clinical trials, contraception mandates, and pregnancy testing during the course of a study.