Cryptic colonization and transmission of mcr-1-positive Escherichia coli in mouse intestines

Abstract

Background Mobile colistin-resistance gene mcr-1 is prevalent among various bacteria, hosts and countries, especially in the guts of humans and animals. However, the biological basis for mcr-1 colonization and transmission in the intestines is largely unknown. Methods We used mouse models to mimic exposure to mcr-1-positive Escherichia coli (MCRPEC, harboring an IncI2 plasmid positive for mcr-1) in human intestines without and with antibiotic pretreatment, respectively. We used cultivation and qPCR method to determine the presence and quantity of MCRPEC. We also used Fluorescence in situ hybridization (FISH) method to locate mcr-1-positive bacteria in situ and confocal laser scanning microscopy method to examine the interaction between MCRPEC and Caco-2 cell in vitro. Finally, we used mouse model to investigate the transmission of MCRPEC among individuals. Results We found two approaches of MCRPEC colonization in the mouse intestines after exposure. In mice with intestinal microbiota homeostasis, MCRPEC was transient in the large intestines, while mcr-1 was detected at lower abundances (10-4–10-5) for at least 21 days as relic DNA or mcr-1-positive uncommon bacteria (MCRPUB). In mice with intestinal microbiota dysbiosis, MCRPEC colonized the intestines directly with a high shedding load (~108 CFU/g feces) and high mcr-1 abundance (~10-2). The transmission model confirmed that both MCRPEC and MCRPUB could cryptically transfer among individuals and persist for long periods. Conclusions These results demonstrate two approaches of MCRPEC colonization and a long persistence of MCRPUB or an antetype in mouse intestines as well as their transmission among mice, which partially explains the widespread prevalence of mcr-1-positive IncI2 plasmid among hosts and its long persistence in the gut even without antibiotic pressure. Contaminated food enables exposure to pathogens that can colonize human intestines; thus, reducing MCRPEC/MCRPUB in livestock and animal-derived food and preventing MCRPEC/MCRPUB transmission in ecosystems under the "One Health" perspective are crucial.