Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility

GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits

© 2019, The Author(s). Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits

Enzymatic degradation of in vitro Staphylococcus aureus biofilms supplemented with human plasma

Chase M Watters,1,2 Tarea Burton,1 Dickson K Kirui,1 Nancy J Millenbaugh1 1Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA; 2Wound Infections Department, Naval Medical Research Center, Silver Spring, MD, USA Abstract: Enzymatic debridement is a therapeutic strategy used clinically to remove necrotic tissue from wounds. Some of the enzymes utilized for debridement have been tested against bacterial pathogens, but the effectiveness of these agents in dispersing clinically relevant biofilms has not been fully characterized. Here, we developed an in vitro Staphylococcus aureus biofilm model that mimics wound-like conditions and employed this model to investigate the antibiofilm activity of four enzymatic compounds. Human plasma at concentrations of 0%–50% was supplemented into growth media and used to evaluate biofilm biomass accumulation over 24 hours and 48 hours in one methicillin-sensitive and five methicillin-resistant strains of S. aureus. Supplementation of media with 10% human plasma resulted in the most robust biofilms in all six strains. The enzymes α-amylase, bromelain, lysostaphin, and papain were then tested against S. aureus biofilms cultured in 10% human plasma. Quantification of biofilms after 2 hours and 24 hours of treatment using the crystal violet assay revealed that lysostaphin decreased biomass by up to 76%, whereas a-amylase, bromelain, and papain reduced biomass by up to 97%, 98%, and 98%, respectively. Scanning electron microscopy confirmed that the dispersal agents detached the biofilm exopolysaccharide matrix and bacteria from the growth surface. Lysostaphin caused less visible dispersal of the biofilms, but unlike the other enzymes, induced morphological changes indicative of bacterial cell damage. Overall, our results indicate that use of enzymes may be an effective means of eradicating biofilms and a promising strategy to improve treatment of multidrug-resistant bacterial infections. Keywords: MRSA, α-amylase, bromelain, lysostaphin, papai

Photothermal killing of Staphylococcus aureus using antibody-targeted gold nanoparticles

Nancy J Millenbaugh,1 Jonathan B Baskin,1 Mauris N DeSilva,1 W Rowe Elliott,1 Randolph D Glickman2 1Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA; 2Department of Ophthalmology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USAPurpose: The continued emergence of multidrug resistant bacterial infections and the decline in discovery of new antibiotics are major challenges for health care throughout the world. This situation has heightened the need for novel antimicrobial therapies as alternatives to traditional antibiotics. The combination of metallic nanoparticles and laser exposure has been proposed as a strategy to induce physical damage to bacteria, regardless of antibiotic sensitivity. The purpose of this study was to test the antibacterial effect of antibody-targeted gold nanoparticles combined with pulsed laser irradiation.Methods: Gold nanoparticles conjugated to antibodies specific to Staphylococcus aureus peptidoglycan were incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA). Bacterial suspensions were then exposed to 8 ns pulsed laser irradiation at a wavelength of 532 nm and fluences ranging from 1 to 5 J/cm2. Viability of the bacteria following laser exposure was determined using colony forming unit assays. Scanning electron microscopy was used to confirm the binding of nanoparticles to bacteria and the presence of cellular damage.Results: The laser-activated nanoparticle treatment reduced the surviving population to 31% of control in the MSSA population, while the survival in the MRSA population was reduced to 58% of control. Significant decreases in bacterial viability occurred when the laser fluence exceeded 1 J/cm2, and this effect was linear from 0 to 5 J/cm2 (r2=0.97). Significantly less bactericidal effect was observed for nonfunctionalized nanoparticles or functionalized nanoparticles without laser activation.Conclusion: Laser-activated nanoparticles targeted to S. aureus surface antigens significantly reduced the percentage of viable organisms and represents a promising new treatment modality that could be used either alone or as an adjunct to existing, conventional antibiotic therapy. Keywords: MRSA, bacteria, pulsed laser, nanospheres, photoacousti

Interspecific Comparison and annotation of two complete mitochondrial genome sequences from the plant pathogenic fungus Mycosphaerella graminicola

The mitochondrial genomes of two isolates of the wheat pathogen Mycosphaerella graminicola were sequenced completely and compared to identify polymorphic regions. This organism is of interest because it is phylogenetically distant from other fungi with sequenced mitochondrial genomes and it has shown discordant patterns of nuclear and mitochondrial diversity. The mitochondrial genome of M. graminicola is a circular molecule of approximately 43,960 bp containing the typical genes coding for 14 proteins related to oxidative phosphorylation, one RNA polymerase, two rRNA genes and a set of 27 tRNAs. The mitochondrial DNA of M. graminicola lacks the gene encoding the putative ribosomal protein (rps5-like), commonly found in fungal mitochondrial genomes. Most of the tRNA genes were clustered with a gene order conserved with many other ascomycetes. A sample of thirty-five additional strains representing the known global mt diversity was partially sequenced to measure overall mitochondrial variability within the species. Little variation was found, confirming previous RFLP-based findings of low mitochondrial diversity. The mitochondrial sequence of M. graminicola is the first reported from the family Mycosphaerellaceae or the order Capnodiales. The sequence also provides a tool to better understand the development of fungicide resistance and the conflicting pattern of high nuclear and low mitochondrial diversity in global populations of this fungus