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Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-binding protein (SilE) and two efflux pumps (a P-type ATPase (SilP) plus a three-protein chemiosmotic RND Ag(I)/H + exchange system (SilCBA)). The same genes were identified on five of 19 additional IncH incompatibility class plasmids but thus far not on other plasmids. Of 70 random enteric isolates from a local hospital, isolates from catheters and other Ag-exposed sites, and total genomes of enteric bacteria, 10 have recognizable sil genes. The centrally located six genes are found and functional in the chromosome of Escherichia coli K-12, and also occur on the genome of E. coli O157:H7. The use of molecular epidemiological tools will establish the range and diversity of such resistance systems in clinical and non-clinical sources. Silver compounds are used widely as effective antimicrobial agents to combat pathogens (bacteria, viruses and eukaryotic microorganisms) in the clinic and for public health hygiene. Silver cations (Ag +) are microcidal at low concentrations and used to treat burns, wounds and ulcers. Ag is used to coat catheters to retard microbial biofilm development. Ag is used in hygiene products including face creams, ‘alternative medicine’ health supplements, supermarket products for washing vegetables, and water filtration cartridges. Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern.

Caries is the most ubiquitous infectious disease of mankind, and early childhood caries (ECC) is the most prevalent chronic disease in children worldwide, with the resulting destruction of the teeth recognized as a global health crisis. Recent the United States Food and Drug Administration (FDA) approval for the use of silver diamine fluoride (SDF) in dentistry offers a safe, accessible, and inexpensive approach to arrest caries progression in children with ECC. However, discoloration, i.e., black staining, of demineralized or cavitated surfaces treated with SDF has limited its widespread use. Targeting SDF-treated tooth surfaces, we developed a biohybrid calcium phosphate nanocomposite interface building upon the self-assembly of synthetic biomimetic peptides. Here, an engineered bifunctional peptide composed of a silver binding peptide (AgBP) is covalently joined to an amelogenin derived peptide (ADP). The AgBP provides anchoring to the SDF-treated tooth tissue, while the ADP promotes rapid formation of a calcium phosphate isomorph nanocomposite mimicking the biomineralization function of the amelogenin protein. Our results demonstrate that the bifunctional peptide was effective in remineralizing the biomineral destroyed by caries on the SDF-treated tooth tissues. The proposed engineered peptide approach offers a biomimetic path for remineralization of the SDF-treated tissues producing a calcium phosphate nanocomposite interface competent to be restored using commonly available adhesive dental composites.

The octapeptide NAP (NAPVSIPQ) is a small sequence from the activity-dependent neuroprotective protein (ADNP), which is able to provide neuroprotection against Aβ toxicity even at low concentration. NAP provides protection against oxidative stress to brain cells and stimulates neurite outgrowth providing a neurotrophic and neuroprotective function. Therefore, we have investigated copper and silver binding to two NAP-like peptides, since our previous research revealed unexpected iron binding to such peptides. Here, we report on Cu(I) and Ag(I) binding to NAP and its Cys 5 mutant. Our results revealed that NAP bind up to two silver ions but only one of copper as shown by Fourier transform infrared (FTIR) spectroscopy and MALDI-ToF mass spectrometry (MS). Surprisingly, its Cys 5 mutant can bind four silver ions or three of copper, despite the fact that it is a small peptide molecule. The results were discussed in the view of NAP protection against Aβ induced neurotoxicity associated with Alzheimer disease (AD) and the relationship between Aβ peptides and heavy metal ions.

To develop novel elastin-like materials with antibacterial capabilities. Artificial proteins bearing AG3 silver-binding motifs (GPG-AG3) were constructed using genetic engineering. GPG-AG3 materials were prepared as GPG-AG3 protein aggregates as well as chemically crosslinked spin-coated thin films. Both GPG-AG3 protein aggregates and thin films were incubated in silver nitrate solution and characterized using electron microscopy. The GPG-AG3 substrates prepared in this work have the ability to nucleate silver under physiological conditions. When tested against gram-negative bacterial culture, silver-coated GPG-AG3 materials were able to inhibit bacterial growth, confirming their antibacterial properties. Antibacterial artificial protein materials were successfully developed, demonstrating promise for use as wound dressings and biomedical implant coatings.