Antimicrobial and Antibiofilm Activities of Helical Antimicrobial Peptide Sequences Incorporating Metal-Binding Motifs.

Antimicrobial peptides (AMPs) represent alternative strategies to combat the global health problem of antibiotic resistance. However, naturally occurring AMPs are generally not sufficiently active for use as antibiotics. Optimized synthetic versions incorporating additional design principles are needed. Here, we engineered amino-terminal Cu(II) and Ni(II) (ATCUN) binding motifs, which can enhance biological function, into the native sequence of two AMPs, CM15 and citropin1.1. The incorporation of metal-binding motifs modulated the antimicrobial activity of synthetic peptides against a panel of carbapenem-resistant enterococci (CRE) bacteria, including carbapenem-resistant Klebsiella pneumoniae (KpC+) and Escherichia coli (KpC+). Activity modulation depended on the type of ATCUN variant utilized. Membrane permeability assays revealed that the in silico selected lead template, CM15, and its ATCUN analogs increased bacterial cell death. Mass spectrometry, circular dichroism, and molecular dynamics simulations indicated that coordinating ATCUN derivatives with Cu(II) ions did not increase the helical tendencies of the AMPs. CM15 ATCUN variants, when combined with Meropenem, streptomycin, or chloramphenicol, showed synergistic effects against E. coli (KpC+ 1812446) biofilms. Motif addition also reduced the hemolytic activity of the wild-type AMP and improved the survival rate of mice in a systemic infection model. The dependence of these bioactivities on the particular amino acids of the ATCUN motif highlights the possible use of size, charge, and hydrophobicity to fine-tune AMP biological function. Our data indicate that incorporating metal-binding motifs into peptide sequences leads to synthetic variants with modified biological properties. These principles may be applied to augment the activities of other peptide sequences.

Assessment of surface water quality status of the Aby Lagoon System in the Western Region of Ghana.

The pollution status of the Tendo Lagoon, the upstream section of the Aby Lagoon System, was investigated. The water temperature, pH, turbidity, dissolved oxygen (DO), electrical conductivity (EC), nitrates (NO3 -), and phosphate (PO4 3-) levels were evaluated using samples taken during the wet and dry seasons to assess the variabilities in water quality in the area. The water quality data was subjected to paired t-test, One-way ANOVA, Factor Analysis, Cluster analysis (CA) as well as a Water Quality Index (WQI) evaluation using the Canadian Council of Ministers of the Environment (CCME) model. The paired sample t-test confirmed that the surface water quality varies significantly between the wet and dry season samples (p < 0.05) except for phosphate loads which may be contributed largely by year-round municipal waste discharges. The results of the ANOVA showed that the variation of the water quality parameters among sampling stations was not statistically significant except for turbidity which was relatively higher in the upstream sections where the Tano River enters the lagoon. The results of FA indicated that three significant factors-relating to the degradation of organic materials, suspended solids (turbidity) and nutrients- accounted for 73.65% of spatio-temporal variations in the water quality. The CA showed that the eight sampling stations can be grouped into four distinct clusters based on their water quality. The source of pollution in the demarcated sections of the Aby Lagoon was concluded to be largely due to the result of localized anthropogenic inputs of domestic waste and sediments carried from the upstream in the Tano River. An evaluation of the CCME WQI for the sampling stations revealed that all the sampling stations showed marginal water quality relative to the target water quality range recommended by the Water Resources Commission (WRC) of Ghana for domestic use and protection of aquatic life. Monitoring programs were recommended with effective management measures instituted and implemented for the sustainability of the lagoon and the Tano River Basin.