RESUMEN
Phosphonates are compounds containing a direct carbon-phosphorus (C-P) bond, which is particularly resistant to chemical and enzymatic degradation. They are environmentally ubiquitous: some of them are produced by microorganisms and invertebrates, whereas others derive from anthropogenic activities. Because of their chemical stability and potential toxicity, man-made phosphonates pose pollution problems, and many studies have tried to identify biocompatible systems for their elimination. On the other hand, phosphonates are a resource for microorganisms living in environments where the availability of phosphate is limited; thus, bacteria in particular have evolved systems to uptake and catabolize phosphonates. Such systems can be either selective for a narrow subset of compounds or show a broader specificity. The role, distribution, and evolution of microbial genes and enzymes dedicated to phosphonate degradation, as well as their regulation, have been the subjects of substantial studies. At least three enzyme systems have been identified so far, schematically distinguished based on the mechanism by which the C-P bond is ultimately cleaved-i.e., through either a hydrolytic, radical, or oxidative reaction. This review summarizes our current understanding of the molecular systems and pathways that serve to catabolize phosphonates, as well as the regulatory mechanisms that govern their activity.
Asunto(s)
Liasas , Organofosfonatos , Humanos , Organofosfonatos/química , Liasas/genética , Bacterias/metabolismo , Fósforo/metabolismo , Fosfatos/químicaRESUMEN
Introduction: Poor adherence to medication regimens accounts for the substantial worsening of disease, death, and increased healthcare costs of approximately $100 billion annually in the United States. Patients participating in medication synchronization had 3.4 to 6.1 times increased odds of adherence, depending on the drug class. Abundant literature supports medication synchronization within the adult population. This IRB-exempt, prospective quality improvement project is an example of implementing and assessing medication synchronization inclusive of the pediatric setting. Methods: This study is a single-center, prospective, quality improvement project for patients seen at Nationwide Children's Hospital (NCH) Complex Care Clinic that also fill prescriptions at NCH Outpatient Pharmacies. The project assessed patient medication adherence using the Proportion of Days Covered and the number of trips to the pharmacy 90 days before and 90 days postimplementation. We also assessed patient and pharmacy staff satisfaction 3 months after project implementation. Results: There was a statistically significant increase in the number of days covered for patients 90 days postimplementation compared to 90 days before implementation (Difference: 3.60; 95% confidence interval: 1.87, 5.33; P = 0.001). Additionally, there was a statistically significant decrease in pharmacy trips pre- and postimplementation (Difference: 2.17; 95% confidence interval: 1.26, 3.07; P < 0.001). Overall, pharmacy staff and patients reported satisfaction with the service. Conclusions: Implementing a medication synchronization service improved medication adherence and decreased trips to the pharmacy within the pediatric population.
RESUMEN
Methane is a potent greenhouse gas in the atmosphere, and its concentration has continued to increase in recent decades. Aerobic methanotrophs, bacteria that use methane as the sole carbon source, are an important biological sink for methane, and they are widely distributed in the natural environment. However, relatively little is known on how methanotroph activity is regulated by nutrients, particularly phosphorus (P). P is the principal nutrient constraining plant and microbial productivity in many ecosystems, ranging from agricultural land to the open ocean. Using a model methanotrophic bacterium, Methylosinus trichosporium OB3b, we demonstrate here that this bacterium can produce P-free glycolipids to replace membrane phospholipids in response to P limitation. The formation of the glycolipid monoglucuronic acid diacylglycerol requires plcP-agt genes since the plcP-agt mutant is unable to produce this glycolipid. This plcP-agt-mediated lipid remodeling pathway appears to be important for M. trichosporium OB3b to cope with P stress, and the mutant grew significantly slower under P limitation. Interestingly, comparative genomics analysis shows that the ability to perform lipid remodeling appears to be a conserved trait in proteobacterial methanotrophs; indeed, plcP is found in all proteobacterial methanotroph genomes, and plcP transcripts from methanotrophs are readily detectable in metatranscriptomics data sets. Together, our study provides new insights into the adaptation to P limitation in this ecologically important group of bacteria. IMPORTANCE Methane is a potent greenhouse gas in the atmosphere, and its concentration has continued to increase steadily in recent decades. In the natural environment, bacteria known as methanotrophs help mitigate methane emissions at no cost to human beings. However, relatively little is known regarding how methane oxidation activity in methanotrophs is regulated by soil nutrients, particularly phosphorus. Here, we show that methanotrophs can modify their membrane in response to phosphorus limitation and that the ability to change membrane lipids is important for methanotroph activity. Genome and metatranscriptome analyses suggest that such an adaptation strategy appears to be strictly conserved in all proteobacterial methanotrophs and is used by these bacteria in the natural environment. Together, our study provides a plausible molecular mechanism for better understanding the role of phosphorus on methane oxidation in the natural environment.