The Synergy between Zinc and Antimicrobial Peptides: An Insight into Unique Bioinorganic Interactions.

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years, as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides represents a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interacts with metal ions to potentiate antimicrobial effectiveness, and, as such, they have been termed metalloAMPs. In this work, we review the scientific literature on metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion zinc(II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate its activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics.

Exploring synergy and its role in antimicrobial peptide biology.

Antimicrobial peptides will be an essential component in combating the escalating issue of antibiotic resistance. Identifying synergistic combinations of two or more substances will increase the value of these peptides further. Several potential pitfalls in conducting synergy testing with peptides are discussed in detail. As case studies, we describe observations of AMP synergy with peptides, antibiotics, and metal ions as well as some of the mechanistic details that have been uncovered. The Bliss and Loewe models for synergy are presented prior to recommending protocols for conducting checkerboard, minimal inhibitory concentration, and time-kill assays. Establishing mechanisms of action and exploring the potential for resistance will be crucial to translate these studies into the clinic.

Identification and Characterization of a DmoB Flavin Oxidoreductase from a Putative Two-Component DMS C-Monooxygenase.

The compound dimethyl sulfide (DMS) links terrestrial and oceanic sulfur with the atmosphere because of its volatility. Atmospheric DMS is responsible for cloud formation and radiation backscattering and has been implicated in climate control mitigation. The enzyme DMS C-monooxygenase degrades DMS and has been classified as a two-component FMNH2-dependent monooxygenase. This enzyme requires a flavin reductase B subunit to supply electrons to the monooxygenase A subunit where DMS conversion occurs. One form of the enzyme from Hyphomicrobium sulfonivorans has been isolated and characterized. In this work, a putative DMS C-monooxygenase has been identified with bioinformatics in Arthrobacter globiformis. We report the expression, purification, and characterization of the DmoB flavin reductase subunit, termed DmoB, from A. globiformis. Data support DmoB preference and optimal activity for the cosubstrates flavin mononucleotide (FMN) and NADH. FMN binds at a 1:1 stoichiometry with high affinity (K d = 1.11 µM). The reductase is able to generate product with the A subunit from H. sulfonivorans expressed in Escherichia coli, albeit at a lower turnover than the natively expressed enzyme. No static protein-protein interactions were observed under the conditions tested between the two subunits. These results provide new details in the classification of enzymes involved in the sulfur cycling pathway and emerging forms of the enzyme DMS monooxygenase.

Physiological and health characteristics of ex-jockeys.

OBJECTIVES: The long-term health implications resulting from extreme and chronic weight cycling and the associated energy restricted lifestyle of a professional jockey remain unknown. The aim of the present study was to describe and evaluate the physiological and health characteristics of retired jockeys. DESIGN: Cross-sectional. METHODS: Retired male jockeys (n=28; age 59±6yr; height 1.65±0.03m; body mass 73.7±10.9kg; BMI 26.9±3.8kgm(-2)) participated. Body composition (by dual energy X-ray absorptiometry; DXA), resting metabolic rate (RMR), glucose metabolism (by oral glucose tolerance test; OGTT), lipids and thyroid function were assessed. All data were interpreted in relation to established age specific reference ranges for the particular assessment undertaken. RESULTS: Forty three percent of the retired jockeys were classified as overweight, while 21% were obese. RMR was calculated as 1447±201kcalday(-1). Mean total cholesterol was 5.93±1.5mmolL(-1) for those not on cholesterol lowering medication and 5.09±1.1mmolL(-1) for those currently taking medication. No abnormalities in glucose metabolism and thyroid function were found. CONCLUSIONS: Chronic weight cycling during a career as a professional jockey did not induce any health consequences in the retired jockeys assessed in this study, however enhanced weight gain and dyslipidaemia were evident. Results suggest jockeys should be tracked longitudinally throughout their racing career and beyond to further establish long-term physical health implications associated with the current lifestyle of a professional jockey.

The effect of vitamin D supplementation on arterial stiffness in an elderly community-based population.

Vitamin D deficiency may lead to impaired vascular function and abnormalities in central arterial stiffness. We compared the effects of two different doses of vitamin D3 on arterial stiffness in an elderly population with deficient serum 25-hydroxy-vitamin D levels. A total of 119 known vitamin D deficient (<50 nmol/L) subjects were randomized to receive either 50,000 international units (IU) or 100,000 IU single intramuscular vitamin D3. In the group that received 100,000 IU vitamin D, median pulse wave velocity decreased from 12.2 m/s (range, 5.1-40.3 m/s) to 11.59 m/s (range, 4.3-14.9 m/s) after 8 weeks (P = .22). A mean decrease of 3.803 ± 1.7 (P = .032) in augmentation index (a measure of systemic stiffness) was noted. Only 3/51 (5.8%) who received 100,000 IU vitamin D reached levels of sufficiency (>75 nmol/L). A significant decrease in augmentation index was seen in the group that received 100,000 IU vitamin D. Serum levels of 25-hydroxy-vitamin D were still deficient at 8 weeks in the majority of patients, which may be attributable to impaired bioavailability.