Transcontinental Dissemination of Enterobacterales Harboring blaNDM-1 in Retail Frozen Shrimp.

The global food trade provides a means of disseminating antimicrobial resistant (AMR) bacteria and genes. Using selective media, carbapenem-resistant species of Enterobacterales (Providencia sp. and Citrobacter sp.), were detected in a single package of imported frozen shrimp purchased from a grocery store in Ohio, USA. Polymerase chain reaction confirmed that both isolates harbored blaNDM-1 genes. Following PacBio long read sequencing, the sequences were annotated using the NCBI Prokaryotic Genome Annotation Pipeline. The blaNDM-1 genes were found in IncC plasmids, each with different antimicrobial resistance island configuration. We found that the blaNDM-1 AMR islands had close relationships with previously reported environmental, food, and clinical isolates detected in Asia and the United States, highlighting the importance of the food chain in the global dissemination of antimicrobial resistance.

A complex cyclical One Health pathway drives the emergence and dissemination of antimicrobial resistance.

Since their commercialization, scientists have known that antimicrobial use kills or inhibits susceptible bacteria while allowing resistant bacteria to survive and expand. Today there is widespread antimicrobial resistance (AMR), even to antimicrobials of last resort such as the carbapenems, which are reserved for use in life-threatening infections. It is often convenient to assign responsibility for this global health crisis to the users and prescribers of antimicrobials. However, we know that animals never treated with antimicrobials carry clinically relevant AMR bacteria and genes. The causal pathway from bacterial susceptibility to resistance is not simple, and dissemination is cyclical rather than linear. Amplification of AMR occurs in healthcare environments and on farms where frequent exposure to antimicrobials selects for resistant bacterial populations. The recipients of antimicrobial therapy release antimicrobial residues, resistant bacteria, and resistance genes in waste products. These are reduced but not removed during wastewater and manure treatment and enter surface waters, soils, recreational parks, wildlife, and fields where animals graze and crops are grown for human and animal consumption. The cycle is complete when a patient carrying AMR bacteria is treated with antimicrobials that amplify the resistant bacterial populations. Reducing the development and spread of AMR requires a One Health approach with the combined commitment of governments, medical and veterinary professionals, agricultural industries, food and feed processors, and environmental scientists. In this review and in the companion Currents in One Health by Ballash et al, JAVMA, April 2024, we highlight just a few of the steps of the complex cyclical causal pathway that leads to the amplification, dissemination, and maintenance of AMR.

The One Health dissemination of antimicrobial resistance occurs in both natural and clinical environments.

Once considered to be a simple cause-and-effect relationship with localized impact, the concept of how antimicrobial use drives antimicrobial resistance is now recognized as a complex, transdisciplinary problem on a global scale. While the issue of antimicrobial resistance is often studied and addressed at the antimicrobial-human or antimicrobial-animal treatment interface, the role of the environment in the One Health dynamics of antimicrobial resistance is not as well understood. Antimicrobial-resistant bacteria, including those resistant to carbapenem drugs, are emerging in veterinary clinical environments, on farms, and in natural habitats. These multidrug-resistant bacteria can colonize our livestock and companion animals and are later disseminated into the environment, where they contaminate surface waters and colonize wildlife. From here, the One Health transmission cycle of antimicrobial-resistant bacteria is completed as environmental reservoirs can serve as sources of antimicrobial resistance transmission into human or animal healthcare settings. In this review, we utilize a One Health perspective to evaluate how environments become contaminated and, in turn, become reservoirs that can colonize and infect our veterinary species, and how the veterinary field is combating environmental contamination with antimicrobial stewardship regulations and program implementation. The companion Currents in One Health by Parker et al, AJVR, April 2024, addresses the intensive research that justifies this One Health cycle of antimicrobial resistance transmission and emerging techniques that are dissecting the complex interactions at the One Health interface.

Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.

INTRODUCTION: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. METHODS: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. RESULTS: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. CONCLUSION: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.