An official website of the United States government
Natural polysaccharides being investigated for use in the field of drug delivery commonly require the addition of sugars or pretreated biomass for fabrication. Geobacillus sp. strain WSUCF1 is a thermophile capable of secreting natural polymers, termed exopolysaccharides (EPSs), cultivated from cost-effective, non-treated lignocellulosic biomass carbon substrates. This preliminary investigation explores the capabilities of a 5% wt/wt amikacin-loaded film constructed from the crude EPS extracted from the strain WSUCF1. Film samples were seen to be non-cytotoxic to human keratinocytes and human skin-tissue fibroblasts, maintaining cell viability, on average, above 85% for keratinocytes over 72-h during a cell viability assay. The drug release profile of a whole film sample revealed a steady release of the antibiotic up to 12 h. The amikacin eluted by the EPS film was seen to be active against Staphylococcus aureus, maintaining above a 91% growth inhibition over a period of 48 h. Overall, this study demonstrates that a 5% amikacin-EPS film, grown from lignocellulosic biomass, can be a viable option for preventing or combating infections in clinical treatment.
more »
« less
Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
Thermosensitive chitosan hydrogels—renewable, biocompatible materials—have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (β-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low β-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing β-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.
more »
« less
- Award ID(s):
- 1818090
- PAR ID:
- 10228274
- Date Published:
- Journal Name:
- Marine Drugs
- Volume:
- 19
- Issue:
- 3
- ISSN:
- 1660-3397
- Page Range / eLocation ID:
- 144
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)Abstract Buruli ulcer is a neglected tropical disease caused by the environmental pathogen, Mycobacterium ulcerans whose major virulence factor is mycolactone, a lipid cytotoxic molecule. Buruli ulcer has high morbidity, particularly in rural West Africa where the disease is endemic. Data have shown that infected lesions of Buruli ulcer patients can be colonized by quorum sensing bacteria such as Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa , but without typical pathology associated with those pathogens’ colonization. M. ulcerans pathogenesis may not only be an individual act but may also be dependent on synergistic or antagonistic mechanisms within a polymicrobial network. Furthermore, co-colonization by these pathogens may promote delayed wound healing, especially after the initiation of antibiotic therapy. Hence, it is important to understand the interaction of M. ulcerans with other bacteria encountered during skin infection. We added mycolactone to S. aureus and incubated for 3, 6 and 24 h. At each timepoint, S. aureus growth and hemolytic activity was measured, and RNA was isolated to measure virulence gene expression through qPCR and RNASeq analyses. Results showed that mycolactone reduced S. aureus hemolytic activity, suppressed hla promoter activity, and attenuated virulence genes, but did not affect S. aureus growth . RNASeq data showed mycolactone greatly impacted S. aureus metabolism. These data are relevant and significant as mycolactone and S. aureus sensing and response at the transcriptional, translational and regulation levels will provide insight into biological mechanisms of interspecific interactions that may play a role in regulation of responses such as effects between M. ulcerans , mycolactone, and S. aureus virulence that will be useful for treatment and prevention.more » « less
-
While biopolymers have the potential to enhance agrochemical delivery and mitigate environmental impacts such as runoff, previous plant studies have often been limited to examining single biopolymers in isolation. This approach has hindered effective comparisons of plant outcomes due to variations in plant type, growth duration, and soil characteristics. The current study addresses this gap by incorporating six separate milled biopolymers: pectin, starch, chitosan, polycaprolactone (PCL), polylactic acid (PLA), or polyhydroxybutyrate (PHB) into soil and directly comparing their impacts on tomato (Solanum lycopersicum) plants cultivated under identical environmental parameters. Plant outcomes were also studied when biopolymers were modified via the inclusion of two phosphorus (P) salts, forming two types of Polymer-P-containing salt composites with amorphous CaPO4 (CaP) and CaHPO4 (DCP). Our results revealed that chitosan-based treatments significantly improved tomato root and shoot biomass, with increases of 200–300% compared to the control plants. Chitosan-CaP and Chitosan-DCP also enhanced P uptake, though the effect was significantly more pronounced in the former, suggesting a synergy between chitosan and CaP. Neither Chitosan-P-containing salt treatment, however, mitigated P leaching from soil when compared to CaP or DCP applied in isolation. The two most hydrophilic biopolymers, pectin and starch, as well as their P-salt-containing counterparts, showed the most substantial reductions in biomass (∼80%) with respect to control plants, while similarly lowering P uptake and P retention in soil compared to CaP- and DCP-only plants. PCL- and PHB-based treatments also adversely influenced biomass and plant P, though these effects were not as drastic as those observed with pectin and starch. PLA-based soil amendments had no effect on any plant performance metric, though PLA-CaP, specifically, was the only treatment to appreciably mitigate P leaching (−63%). Based on these findings, subsequent tomato growth experiments were conducted over a longer 8-week period with CaP, DCP, Chitosan, Chitosan-CaP, and Chitosan-DCP. While all chitosan-treated plants showed similar enhancements in biomass, plants treated with Chitosan-CaP and Chitosan-DCP were the only ones to fruit, demonstrating the benefit of using chitosan in conjunction with a P source as compared to either treatment in isolation. These findings contribute to an expanding body of evidence that biopolymer carriers can offer a more sustainable approach to improving the precision of nutrient delivery, while also highlighting the pivotal role of biopolymer and nutrient type in the development of these carriers.more » « less
-
Abstract The World Health Organization has declared antibiotic resistance “one of the biggest threats to global health.” Mounting evidence suggests that antibiotic use in industrial‐scale hog farming is contributing to the spread of antibiotic‐resistantStaphylococcus aureus. To capture available evidence on these risks, we searched peer‐reviewed studies published before June 2017 and conducted a meta‐analysis of these studies’ estimates of the prevalence of swine‐associated, antibiotic‐resistantS. aureusin animals, humans, and the environment. The 166 relevant studies revealed consistent evidence of livestock‐associated methicillin‐resistantS. aureus(MRSA) in hog herds (55.3%) raised with antibiotics. MRSA prevalence was also substantial in slaughterhouse pigs (30.4%), industrial hog operation workers (24.4%), and veterinarians (16.8%). The prevalence of swine‐associated, multidrug‐resistantS. aureus(MDRSA)—with resistance to three or more antibiotics—is not as well documented. Nonetheless, sufficient studies were available to estimate MDRSA pooled prevalence in conventional hog operation workers (15.0%), workers’ household members (13.0%), and community members (5.37%). Evidence also suggests that antibiotic‐resistantS. aureuscan be present in air, soil, water, and household surface samples gathered in or near high‐intensity hog operations. An important caveat is that prevalence estimates for humans reflect colonization, not active infection, and the health risks of colonization remain poorly understood. In addition, these pooled results may not represent risks in specific locations, due to wide geographic variation. Nonetheless, these results underscore the need for additional preventive action to stem the spread of antibiotic‐resistant pathogens from livestock operations and a streamlined reporting system to track this risk.more » « less
-
null (Ed.)The effect of static silica particles on the dynamics of quantum dot (QD) nanoparticles grafted with a poly(ethylene glycol) (PEG) brush in hydrogel nanocomposites is investigated using single particle tracking (SPT). At a low volume fraction of homogeneously dispersed silica ( Φ = 0.005), two distinct populations of PEG-QDs are observed, localized and mobile, whereas almost all PEG-QDs are mobile in neat hydrogel ( Φ = 0.0). Increasing the silica particle concentration ( Φ = 0.01, 0.1) results in an apparent change in the network structure, confounding the impact of silica on PEG-QD dynamics. The localized behavior of PEG-QDs is attributed to pH-mediated attraction between the PEG brush on the probe and surface silanol groups of silica. Using quartz crystal microbalance with dissipation (QCM-D), the extent of this interaction is investigated as a function of pH. At pH 5.8, the PEG brush on the probe can hydrogen bond with the silanol groups on silica, leading to adsorption of PEG-QDs. In contrast, at pH 9.2, silanol groups are deprotonated and PEG-QD is unable to hydrogen bond with silica leading to negligible adsorption. To test the effect of pH, PEG-QD dynamics are further investigated in hydrogel nanocomposites at Φ = 0.005. SPT agrees with the QCM-D results; at pH 5.8, PEG-QDs are localized whereas at pH 9.2 the PEG-QDs are mobile. This study provides insight into controlling probe transport through hydrogel nanocomposites using pH-mediated interactions, with implications for tuning transport of nanoparticles underlying drug delivery and nanofiltration.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/md19030144
