Self-transmissible and mobilizable plasmids contribute to the emergence and spread of multidrug-resistant bacteria by enabling the horizontal transfer of acquired antibiotic resistance. The objective of this study was to capture and characterize self-transmissible and mobilizable resistance plasmids from a coastal wetland impacted by urban stormwater runoff and human wastewater during the rainy season. Four plasmids were captured, two self-transmissible and two mobilizable, using both mating and enrichment approaches. Plasmid genomes, sequenced with either Illumina or PacBio platforms, revealed representatives of incompatibility groups IncP-6, IncR, IncN3, and IncF. The plasmids ranged in size from 36 to 144 kb and encoded known resistance genes for most of the major classes of antibiotics used to treat Gram-negative infections (tetracyclines, sulfonamides, β-lactams, fluoroquinolones, aminoglycosides, and amphenicols). The mobilizable IncP-6 plasmid pLNU-11 was discovered in a strain of Citrobacter freundii enriched from the wetland sediments with tetracycline and nalidixic acid, and encodes a novel AmpC-like β-lactamase (blaWDC-1), which shares less than 62% amino acid sequence identity with the PDC class of β-lactamases found in Pseudomonas aeruginosa. Although the IncR plasmid pTRE-1611 was captured by mating wetland bacteria with P. putida KT2440 as recipient, it was found to be mobilizable rather than self-transmissible. Two self-transmissible multidrug-resistance plasmids were also captured: the small (48 kb) IncN3 plasmid pTRE-131 was captured by mating wetland bacteria with Escherichia coli HY842 where it is seemed to be maintained at nearly 240 copies per cell, while the large (144 kb) IncF plasmid pTRE-2011, which was isolated from a cefotaxime-resistant environmental strain of E. coli ST744, exists at just a single copy per cell. Furthermore, pTRE-2011 bears the globally epidemic blaCTX-M-55 extended-spectrum β-lactamase downstream of ISEcp1. Our results indicate that urban coastal wetlands are reservoirs of diverse self-transmissible and mobilizable plasmids of relevance to human health.
While antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the simian immunodeficiency virus (SIV) model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, anti-viral immunity, viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses. Marked clearance of SIV-positive cells from gut mucosal effector sites was correlated with robust regeneration of germinal centers (GC), restoration of follicular B cells, T follicular helper (Tfh) cells, and enhanced antigen presentation by viral trapping within follicular dendritic cell network. Gut transcriptomic analyses showed increased antiviral response mediated by unique pathways of type-I/II IFN signaling, viral restriction factors, innate immunity and B cell proliferation and provided the molecular signature underlying enhanced host immunity. Metabolic analysis revealed strong correlations between B and Tfh cell activation, anti-SIV antibodies, and IL-7 expression with enriched retinol metabolism, which facilitates gut homing of antigen-activated lymphocytes. Our findings discover new MSC functions in modulating anti-viral immunity for enhanced viral clearance predominantly through type-I/II IFN signaling and B cell signature and provide a roadmap for multi-pronged HIV eradication strategies.
DSORPTION on activated charcoal has been used by the petroleum industry for a number of years in field and laboratory tests for heavier hydrocarbon content of natural gases, Also of importance is the separation of light hydrocarbon mixtures on a commercial scale by adsorption on charcoal. The development of these processes depends on equilibrium adsorption data for the mixtures involved. Few such data appear in the literature. The purpose of the present investigation was t o provide additional equilibrium data and to determine whether characteristics of a charcoal could be established which would a t a given temperature and pressure permit prediction of vaporadsorbate equilibria for light hydrocarbon mixtures of varying composition.A similar investigation by Lewis and others (W,3) is reported in the literature. These authors used both thermodynamic and adsorption potential methods in an effort to correlate equilibrium data on pure components with data on mixtures. The adsorption potential method was the more successful but was found generally unsatisfactory for mixtures in which the molecular weights of the constituents differed appreciably. Inadequate data prevented further development of their correlations.
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