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Multidrug resistant pathogens respond differently to the presence of co-pathogen, commensal, probiotic and host cells.

Agnes P Chan | Yongwook Choi | Lauren M Brinkac | Radha Krishnakumar | Jessica DePew | Maria Kim | Mary K Hinkle | Emil P Lesho | Derrick E Fouts
Scientific reports | 2018

In light of the ongoing antimicrobial resistance crisis, there is a need to understand the role of co-pathogens, commensals, and the local microbiome in modulating virulence and antibiotic resistance. To identify possible interactions that influence the expression of virulence or survival mechanisms in both the multidrug-resistant organisms (MDROs) and human host cells, unique cohorts of clinical isolates were selected for whole genome sequencing with enhanced assembly and full annotation, pairwise co-culturing, and transcriptome profiling. The MDROs were co-cultured in pairwise combinations either with: (1) another MDRO, (2) skin commensals (Staphylococcus epidermidis and Corynebacterium jeikeium), (3) the common probiotic Lactobacillus reuteri, and (4) human fibroblasts. RNA-Seq analysis showed distinct regulation of virulence and antimicrobial resistance gene responses across different combinations of MDROs, commensals, and human cells. Co-culture assays demonstrated that microbial interactions can modulate gene responses of both the target and pathogen/commensal species, and that the responses are specific to the identity of the pathogen/commensal species. In summary, bacteria have mechanisms to distinguish between friends, foe and host cells. These results provide foundational data and insight into the possibility of manipulating the local microbiome when treating complicated polymicrobial wound, intra-abdominal, or respiratory infections.

Pubmed ID: 29872152

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: U19 AI110819

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Bioconductor (tool)

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