Researchers characterize the effects of microbial interactions on C diff susceptibility to antibiotics

The results of a new study reveal patterns of responses in animals. major intestinal pathogens to antibiotics.

Using diverse human gut communities, researchers investigated how interspecies interactions in the gut microbiota influence gut microbial responses. Clostridioides difficile Vancomycin and metronidazole are antibiotics related to the treatment of pathogens with different spectrums of activity. their discovery say a group of PLoS biologyunderlines the need to consider these biological interactions in future approaches for therapy against pathogens.

“A fundamental question is to clarify the role of biological interactions in shaping antibiotic susceptibility in the microbiome. To understand how to change difference in C It may enable customized antibiotic treatment based on ecological context,” the researchers explained. “This understanding may aid new microbiome interventions that selectively eradicate human pathogens and minimize the acquisition of antibiotic resistance while minimizing disruption of healthy gut microbiota. .”

The researchers identified two sets of interactions that resulted in increased interactions. difference in C Growth in the presence of antibiotics. These interactions include rare effects of the gut microbiome. difference in CMinimum inhibitory concentration (MIC) and general effects of difference in CResponse to Sub-Inhibitory Concentrations of Antibiotics.

The same group used the broth dilution method and found that the MICs were: difference in C Fifteen pairwise communities maintained consistency and five pairwise communities had moderate increases over single species. Remarkably, they found a more than four-fold increase in MIC. difference in C in co-culture with Desulfobiblio girlthe MIC of metronidazole increases from 6 mcg/mL to at least 24 mcg/mL.

“The observed increase was difference in C The MIC of metronidazole in the presence of specific gut may contribute to metronidazole’s ineffectiveness in therapy difference in C infection in the human colon,” the researchers elaborated. “Because of the low concentrations of metronidazole achieved in the human colon, even small increases difference in C Metronidazole MIC may keep pathogens alive.Based on this result, future tests should be difference in C Antibiotic susceptibility may include the following symptoms: difference in C Cultured with a physiologically relevant microbial community. ”

on the other hand, difference in C Infection at sub-suppressive concentrations was observed in 52% of the community.

In the pairwise community, difference in C There was a similar or decreased trend in the minimum inhibitory concentration (subMIC) range compared to the absence of antibiotic. however, Bacteroides thetaiotaomicron, difference in C Abundance was significantly higher in the presence of 0.75 mcg/mL metronidazole than in the absence of antibiotics. In determining the sub-MIC fold change at each sub-MIC, the group difference in C Vancomycin treatment enhanced at least 1 sub-MIC in 1 pairwise community and metronidazole treatment enhanced at least 1 sub-MIC in 11 pairwise communities.Increase Reinforcement difference in C significantly greater than that observed with metronidazole treatment difference in C Monocultures of metronidazole across seven pairwise communities.

The researchers explained that the presence of sub-inhibitory concentrations of antibiotics can occur in several scenarios, such as when pathogens develop resistance to antibiotics and at the beginning and end of a dosing regimen. .

The researchers also conducted metal supplementation experiments, which showed that five metals significantly reduced their intake in the body. difference in C Ministry of Internal Affairs and Communications However, the addition of single metals such as iron did not produce the same effect. Based on this finding, researchers hypothesized that the enzymatic activity leading to metronidazole reduction requires several metal cofactors.

reference

Hromada S, Venturelli O. Interspecies interactions of the gut microbiota shape gut bacterial responses. Clostridioides difficile up to clinically relevant antibiotics. PLoS Biol. Published online May 11, 2023. doi:10.1371/journal.pbio.3002100