Human intestinal bacteria as reservoirs for antibiotic resistance genes.

The mammalian gut harbors a dense microbial community interacting in multiple ways, including horizontal gene transfer (HGT). Pangenome analyses established particularly high levels of genetic flux between Gram-negative Enterobacteriaceae. However, the mechanisms fostering intraenterobacterial HGT are incompletely understood. Using a mouse colitis model, we found that Salmonella-inflicted enteropathy elicits parallel blooms of the pathogen and of resident commensal Escherichia coli. These blooms boosted conjugative HGT of the colicin-plasmid p2 from Salmonella enterica serovar Typhimurium to E. coli. Transconjugation efficiencies of ∼100% in vivo were attributable to high intrinsic p2-transfer rates. Plasmid-encoded fitness benefits contributed little. Under normal conditions, HGT was blocked by the commensal microbiota inhibiting contact-dependent conjugation between Enterobacteriaceae. Our data show that pathogen-driven inflammatory responses in the gut can generate transient enterobacterial blooms in which conjugative transfer occurs at unprecedented rates. These blooms may favor reassortment of plasmid-encoded genes between pathogens and commensals fostering the spread of fitness-, virulence-, and antibiotic-resistance determinants.

https://www.pnas.org/content/pnas/109/4/1269.full.pdf

Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae.

Safety assessment of dairy microorganisms: the Enterococcus genus.

Vancomycin-resistant enterococci (VRE) are both of medical and public health importance associated with serious multidrug-resistant infections and persistent colonization. Enterococci are opportunistic environmental inhabitants with a remarkable adaptive capacity to evolve and transmit antimicrobial-resistant determinants. The VRE gene operons show distinct genetic variability and apparently continued evolution leading to a variety of antimicrobial resistance phenotypes and various environmental and livestock reservoirs for the most common van genes. Such complex diversity renders a number of important therapeutic options including "last resort antibiotics" ineffective and poses a particular challenge for clinical management. Enterococci resistance to glycopeptides and multidrug resistance warrants attention and continuous monitoring.

/pdf/vancomycin-resistant-enterococci-a-review-of-antimicrobial-dkrwxf4i3a.pdf

Vancomycin-Resistant Enterococci: A Review of Antimicrobial Resistance Mechanisms and Perspectives of Human and Animal Health

Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (≥99% nucleotide identity) of mobile ARGs We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens
 IMPORTANCE The development of antibiotic resistance threatens our modern medical achievements The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs) Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes.

It has been proposed that food animals represent the source of glycopeptide resistance genes present in enterococci from humans. We demonstrated the transfer of vanA and of other resistance genes from porcine to human Enterococcus faecium at high frequency in the digestive tract of gnotobiotic mice. Tylosin in the drinking water favored colonization by transconjugants.

Multiple antibiotic resistance gene transfer from animal to human enterococci in the digestive tract of gnotobiotic mice.

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Multiple antibiotic resistance gene transfer from animal to human enterococci in the digestive tract of gnotobiotic mice.