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1. Crossroads of Antibiotic Resistance and Biosynthesis

   https://doi.org/10.1016/j.jmb.2019.06.033  

   Wencewicz, Timothy A. (August 2019, Journal of Molecular Biology)
2. The effects of lead, copper, and iron corrosion products on antibiotic resistant bacteria and antibiotic resistance genes

   https://doi.org/10.1039/D4VA00026A  

   Folvarska, Veronika; Thomson, San Marie; Lu, Zihao; Adelgren, Maya; Schmidt, Adam; Newton, Ryan J; Wang, Yin; McNamara, Patrick J (June 2024, Environmental Science: Advances)

   Antibiotic resistance is a public health crisis. Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are present in drinking water distribution systems. Metals are known selective pressures for antibiotic resistance, and metallic corrosion products are found within drinking water distribution systems due to the corrosion of metal pipes. While corrosion products are a source of metals, the impact of specific corrosion products on antibiotic resistance has not been investigated. The objective of this study was to determine the impact of six corrosion products—CuO, Cu2O, Pb5(PO4)3OH, b-PbO2, Fe3O4, and a-FeOOH—on the abundance of ARB and ARGs. Lab-scale microcosms were seeded with source water from Lake Michigan and amended with individual corrosion products. In general, copper and lead corrosion products increased antibiotic resistance, although not universally across different ARB and ARG types. Concentration and speciation of copper and lead corrosion products were found to have an impact on antibiotic resistance profiles. Meanwhile, iron corrosion products had minimal impact on antibiotic resistance. Overall, this study sheds light on how pipe materials may impact antibiotic resistance as a result of corrosion products. 

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3. Quantifying Antibiotic Distribution in Solid and Liquid Fractions of Manure Using a Two-Step, Multi-Residue Antibiotic Extraction

   https://doi.org/10.3390/antibiotics11121735  

   Poindexter, Carlton; Yarberry, Andrea; Rice, Clifford; Lansing, Stephanie (December 2022, Antibiotics)

   Antibiotic distribution and analysis within liquid and solid fractions of manure are highly variable due to each compound’s respective physiochemical properties. This study developed and evaluated a uniform method extracting 10 antibiotics from 4 antibiotic classes (tetracycline, sulfonamides, macrolides, and β-lactam) from unprocessed manure, solid–liquid separated manure, and composted solids. Through systematic manipulation of previously published liquid chromatography tandem mass spectrometry methods; this study developed an extraction protocol with optimized recovery efficiencies for varied manure substrates. The method includes a two-step, liquid-solid extraction using 10 mL of 0.1 M EDTA-McIlviane buffer followed by 10 mL of methanol. Antibiotics recoveries from unprocessed manure, separated liquids, separated solids, and heat-treated solids using the two-step extraction method had relative standard deviations < 30% for all but ceftiofur. Total antibiotic recoveries were 67–131% for tetracyclines, 56% for sulfonamide, 49–53% for macrolides, and 1.3–66% for β-lactams. This is the first study to use one protocol to assess four classes of antibiotics in liquid and solid manure fractions. This study allowed for more precise risk assessment of antibiotic transport in manure waste stream applied to fields as a liquid or solid compost. 

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4. The ArsQ permease and transport of the antibiotic arsinothricin

   https://doi.org/10.1111/mmi.15045  

   Paul, Ngozi P.; Viswanathan, Thiruselvam; Chen, Jian; Yoshinaga, Masafumi; Rosen, Barry P. (February 2023, Molecular Microbiology)

   Abstract The pentavalent organoarsenical arsinothricin (AST) is a natural product synthesized by the rhizosphere bacteriumBurkholderia gladioliGSRB05.AST is a broad‐spectrum antibiotic effective against human pathogens such as carbapenem‐resistantEnterobacter cloacae.It is a non‐proteogenic amino acid and glutamate mimetic that inhibits bacterial glutamine synthetase. The AST biosynthetic pathway is composed of a three‐gene cluster,arsQML.ArsL catalyzes synthesis of reduced trivalent hydroxyarsinothricin (R‐AST‐OH), which is methylated by ArsM to the reduced trivalent form of AST (R‐AST). In the culture medium ofB. gladioli, both trivalent species appear as the corresponding pentavalent arsenicals, likely due to oxidation in air. ArsQ is an efflux permease that is proposed to transport AST or related species out of the cells, but the chemical nature of the actual transport substrate is unclear. In this study,B. gladioli arsQwas expressed inEscherichia coliand shown to confer resistance to AST and its derivatives. Cells ofE. coliaccumulate R‐AST, and exponentially growing cells expressingarsQtake up less R‐AST. The cells exhibit little transport of their pentavalent forms. Transport was independent of cellular energy and appears to be equilibrative. A homology model of ArsQ suggests that Ser320 is in the substrate binding site. A S320A mutant exhibits reduced R‐AST‐OH transport, suggesting that it plays a role in ArsQ function. The ArsQ permease is proposed to be an energy‐independent uniporter responsible for downhill transport of the trivalent form of AST out of cells, which is oxidized extracellularly to the active form of the antibiotic. 

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5. Semisynthesis of the Organoarsenical Antibiotic Arsinothricin

   https://doi.org/10.1021/acs.jnatprod.0c00522  

   Suzol, Sazzad H.; Hasan Howlader, A.; Galván, Adriana E.; Radhakrishnan, Manohar; Wnuk, Stanislaw F.; Rosen, Barry P.; Yoshinaga, Masafumi (September 2020, Journal of Natural Products)

   null (Ed.)