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1. Risk of Antibiotic‐Resistant Staphylococcus aureus Dispersion from Hog Farms: A Critical Review

   https://doi.org/10.1111/risa.13495  

   George, Alexandra N.; Stewart, Jill R.; Evans, Jessica C.; Gibson, Jacqueline MacDonald (May 2020, Risk Analysis)

   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. 

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2. Structural and functional characterization of three Type B and C chloramphenicol acetyltransferases from Vibrio species

   https://doi.org/10.1002/pro.3793  

   Alcala, Ashley; Ramirez, Guadalupe; Solis, Allan; Kim, Youngchang; Tan, Kemin; Luna, Oscar; Nguyen, Karen; Vazquez, Daniel; Ward, Michael; Zhou, Min; et al (December 2019, Protein Science)

   Abstract Chloramphenicol acetyltransferases (CATs) were among the first antibiotic resistance enzymes identified and have long been studied as model enzymes for examining plasmid‐mediated antibiotic resistance. These enzymes acetylate the antibiotic chloramphenicol, which renders it incapable of inhibiting bacterial protein synthesis. CATs can be classified into different types: Type A CATs are known to be important for antibiotic resistance to chloramphenicol and fusidic acid. Type B CATs are often called xenobiotic acetyltransferases and adopt a similar structural fold to streptogramin acetyltransferases, which are known to be critical for streptogramin antibiotic resistance. Type C CATs have recently been identified and can also acetylate chloramphenicol, but their roles in antibiotic resistance are largely unknown. Here, we structurally and kinetically characterized threeVibrioCAT proteins from a nonpathogenic species (Aliivibrio fisheri) and two important human pathogens (Vibrio choleraeandVibrio vulnificus). We found all three proteins, including one in a superintegron (V. cholerae), acetylated chloramphenicol, but did not acetylate aminoglycosides or dalfopristin. We also determined the 3D crystal structures of these CATs alone and in complex with crystal violet and taurocholate. These compounds are known inhibitors of Type A CATs, but have not been explored in Type B and Type C CATs. Based on sequence, structure, and kinetic analysis, we concluded that theV. choleraeandV. vulnificusCATs belong to the Type B class and theA. fisheriCAT belongs to the Type C class. Ultimately, our results provide a framework for studying the evolution of antibiotic resistance gene acquisition and chloramphenicol acetylation inVibrioand other species. 

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3. Whole-genome sequence of Paenibacillus sp. , isolated from soil, Fort Collins, Colorado, USA

   https://doi.org/10.1128/MRA.00542-23  

   Kiehl, Paris M.; Cagle, Shelby M.; Kinkel, Traci L.; Stenglein, Mark D. (October 2023, Microbiology Resource Announcements)

   Roux, Simon (Ed.)

   ABSTRACT A whole genome sequence of aPaenibacillussp. bacterium isolated from soil in Fort Collins, Colorado was obtained. This bacterium was of particular interest due to its antibiotic potential against Gram-positive pathogen surrogates. 

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4. Heterogenous biofilm mass-transport model replicates periphery sequestration of antibiotics in Pseudomonas aeruginosa PAO1 microcolonies

   https://doi.org/10.1073/pnas.2312995120  

   Prince, Joshua; Jones, A-Andrew D (November 2023, Proceedings of the National Academy of Sciences)

   A model for antibiotic accumulation in bacterial biofilm microcolonies utilizing heterogenous porosity and attachment site profiles replicated the periphery sequestration reported in prior experimental studies onPseudomonas aeruginosa PAO1biofilm cell clusters. TheseP. aeruginosacell clusters are in vitro models of the chronicP. aeruginosainfections in cystic fibrosis patients which display recalcitrance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics fail to penetrate biofilm cell clusters. The physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena better fit observed periphery sequestration data compared to previous models. 

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5. Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with Escherichia coli

   https://doi.org/10.1073/pnas.2016886118  

   Card, Kyle J.; Thomas, Misty D.; Graves, Jr, Joseph L.; Barrick, Jeffrey E.; Lenski, Richard E. (January 2021, Proceedings of the National Academy of Sciences)

   Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely relatedEscherichia colistrains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance. 

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