Antimicrobial metallopeptides with broad nuclease and ribonuclease activity.
Ontology highlight
ABSTRACT:
SUBMITTER: Joyner JC
PROVIDER: S-EPMC3632407 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
Publications
Antimicrobial metallopeptides with broad nuclease and ribonuclease activity.
Joyner Jeff C JC Hodnick W F WF Cowan Ada S AS Tamuly Deepika D Boyd Rachel R Cowan J A JA
Chemical communications (Cambridge, England) 20130205 21
Metallopeptides containing both the complex Cu(2+)-glycyl-glycyl-histidine (Cu-GGH) and the sequence WRWYCR were shown to possess antimicrobial activity against a variety of pathogenic bacteria, as well as bind to and cleave a variety of nucleic acids, suggesting potential mechanisms for antimicrobial activity that involve binding and/or irreversible cleavage of bacterial nucleic acids. ...[more]
Similar Datasets
Project description:Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has a broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7, but regulation of its antimicrobial activity has not been well defined. Here, we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on the antimicrobial activity of RNase 7. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time polymerase chain reaction showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility.
| S-EPMC3981961 | biostudies-literature
Project description:Histatins are salivary histidine-rich cationic peptides, ranging from 7 to 38 amino acid residues in length, that exert a potent killing effect in vitro on Candida albicans. Starting from the C-terminal fungicidal domain of histatin 5 (residues 11-24, called dh-5) a number of substitution analogues were chemically synthesized to study the effect of amphipathicity of the peptide in helix conformation on candidacidal activity. Single substitutions in dh-5 at several positions did not have any effect on fungicidal activity. However, multi-site substituted analogues (dhvar1 and dhvar2) exhibited a 6-fold increased activity over dh-5. In addition, dhvar1 and dhvar2 inhibited the growth of the second most common yeast found in clinical isolates, Torulopsis glabrata, of oral- and non-oral pathogens such as Prevotella intermedia and Streptococcus mutans, and of a methicillin-resistant Staphylococcus aureus. In their broad-spectrum activity, dhvar1 and dhvar2 were comparable to magainins (PGLa and magainin 2), antimicrobial peptides of amphibian origin. Both the fungicidal and the haemolytic activities of dhvar1, dhvar2 and magainins increased at decreasing ionic strength.
| S-EPMC1218634 | biostudies-other
Project description:Previous investigations indicate that ?-melanocyte-stimulating hormone (?-MSH) and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2')-7, Phe-12]-MSH(6-13) sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of ?-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.
| S-EPMC3634028 | biostudies-literature
Project description:Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal long alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the alkyl chains at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited potent and broad-spectrum bactericidal activity against a panel of Gram-positive and Gram-negative bacteria. The polymers only showed very limited hemolytic activity, demonstrating their excellent selectivity. Comprehensive analyses using biochemical and biophysical assays revealed the strong interaction between the polymers and bacteria membranes. Moreover, the polymers also showed strong biofilm inhibition activity and did not readily induce antibiotic resistance. Our results suggest that lipidated polycarbonates could be a new class of antimicrobial agents.
| S-EPMC10848156 | biostudies-literature
Project description:Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7's antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7's antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7's antibacterial activity.
| S-EPMC8592535 | biostudies-literature
Project description:In the present study, an attempt was made to biochemically characterize the antimicrobial substance from the soil isolate designated as RLID 12.1 and explore its potential applications in biocontrol of drug-resistant pathogens. The antimicrobial potential of the wild-type isolate belonging to the genus Bacillus was determined by the cut-well agar assay. The production of antimicrobial compound was recorded maximum at late exponential growth phase. The ultrafiltered concentrate was insensitive to organic solvents, metal salts, surfactants, and proteolytic and nonproteolytic enzymes. The concentrate was highly heat stable and active over a wide range of pH values. Partial purification, zymogram analysis, and TLC were performed to determine the preliminary biochemical nature. The molecular weight of the antimicrobial peptide was determined to be less than 2.5 kDa in 15% SDS-PAGE and in zymogram analysis against Streptococcus pyogenes. The N-terminal amino acid sequence by Edman degradation was partially determined to be T-P-P-Q-S-X-L-X-X-G, which shows very insignificant identity to other antimicrobial peptides from bacteria. The minimum inhibitory concentrations of dialysed and partially purified ion exchange fractions were determined against some selected gram-positive and gram-negative bacteria and some pathogenic yeasts. The presence of three important antimicrobial peptide biosynthesis genes ituc, fend, and bmyb was determined by PCR.
| S-EPMC4144302 | biostudies-literature
Project description:Due to the wide etiology of conjunctivitis, the expensive and time-consuming diagnosis requires new therapeutic strategies with broad-spectrum antimicrobial activity and nonselective mechanisms of action. In this context, eye drops could provide an alternative to conventional antimicrobial therapies. Here, we compare the antibacterial and antiviral activity of Oftasecur and Visuprime, commercially available ophthalmic solutions. Cytotoxicity assay was performed on Vero CCL-81 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test. Antibacterial efficacy was evaluated on Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae by disk diffusion, broth microdilution methods, and time-killing tests. Furthermore, the antiviral activity against HSV-1 was estimated by co-treatment, cell and viral pretreatment and post-treatment, via plaque reduction assay, fluorescence assessment (GFP-engineered HSV-1), and real-time PCR. After 24 h of exposure, Oftasecur and Visuprime showed a volume-inducing 50% of cytotoxicity of 125 and 15.8 μL, respectively Oftasecur and Visuprime induced 90% antibacterial activity in response to mean volume of 10.0 and 4.4 µL for Gram-positive and Gram-negative strains, respectively. Oftasecur exerted bactericidal action on both bacterial populations, while Visuprime was bacteriostatic on Gram-negative strains and slightly bactericidal on Gram-positive bacteria. A major impact on infectivity occurred by exposure of viral particles to the ophthalmic solutions. In detail, 50% of inhibition was verified by exposing the viral particles to 3.12 and 0.84 μL of Oftasecur and Visuprime, respectively, for 1 h. The reduction of the fluorescence and the expression of the viral genes confirmed the recorded antiviral activity. Due to their high antimicrobial efficiency, Oftasecur and Visuprime could represent a valid empirical strategy for the treatment of conjunctivitis.
| S-EPMC9959165 | biostudies-literature
Project description:The rapid emergence of drug resistant bacteria is occurring worldwide, outpacing the development of new antibiotics. It is known that some of the main sources of antibiotics are the bacteria themselves, many of which are secondary metabolites of Gram positive bacteria. Siderophores, which are secondary metabolites, function as natural chelators (e.g., iron). They are produced and secreted by many bacteria and have been experimented on as "carriers" of several types of antibiotics that pass the cell membrane of challenging Gram negative bacteria. Delftibactin A is a non-ribosomal peptide (NRP), which is known to detoxify gold in Delftia spp. and form gold nuggets, and is considered to be a siderophore. In this study we demonstrate that the supernatant from novel environmental isolates of Delftia spp. have antimicrobial activity. We characterized the active fraction and identified delftibactin A as a compound with antimicrobial activity. Delftibactin A exhibits potent antimicrobial activity against Gram positive multi drug resistant (MDR) bacteria like Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin resistant Enterococcus (VRE), and also against the Gram negative pathogens Acinetobacter baumannii and Klebsiella pneumoniae. We discovered that the production of delftibactin A is greatly influenced by temperature. Furthermore, we have demonstrated the possibility of utilizing delftibactin A as a siderophore carrier of toxic metals such as gallium into Gram negative bacteria. These findings expose new opportunities of yet unexploited natural products such as delftibactin A, which have been known for other bacterial uses, as potent factors in the battle against MDR bacteria.
| S-EPMC6808179 | biostudies-literature
Project description:We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance.
| S-EPMC3746764 | biostudies-literature
Project description:The rapid evolution of highly infectious pathogens is a major threat to global public health. In the front line of defense against bacteria, fungi, and viruses, antimicrobial peptides (AMPs) are naturally produced by all living organisms and offer new possibilities for next-generation antibiotic development. However, the low yields and difficulties in the extraction and purification of AMPs have hindered their industry and scientific research applications. To overcome these barriers, we enabled high expression of bomidin, a commercial recombinant AMP based upon bovine myeloid antimicrobial peptide-27. This novel AMP, which can be expressed in Escherichia coli by adding methionine to the bomidin sequence, can be produced in bulk and is more biologically active than chemically synthesized AMPs. We verified the function of bomidin against a variety of bacteria and enveloped viruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), herpes simplex virus (HSV), dengue virus (DENV), and chikungunya virus (CHIKV). Furthermore, based on the molecular modeling of bomidin and membrane lipids, we elucidated the possible mechanism by which bomidin disrupts bacterial and viral membranes. Thus, we obtained a novel AMP with an optimized, efficient heterologous expression system for potential therapeutic application against a wide range of life-threatening pathogens.
| S-EPMC9160972 | biostudies-literature