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

Authors

Agnes P. Chan, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Yongwook Choi, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Lauren M. Brinkac, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Radha Krishnakumar, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Jessica DePew, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Maria Kim, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.
Mary K. Hinkle, Multidrug-resistant organism Repository and Surveillance Network, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States.
Emil P. Lesho, Rochester Regional HealthFollow
Derrick E. Fouts, J. Craig Venter Institute (JCVI), 9605 Medical Center Drive, Suite 150, Rockville, MD, 20850, United States.

Department

Infectious Diseases

Document Type

Article

Publication Title

Scientific Reports

Abstract

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.

First Page

8656

DOI

10.1038/s41598-018-26738-1

Volume

8

Issue

1

Publication Date

6-5-2018

Medical Subject Headings

Bacteria (drug effects, growth & development); Cells, Cultured; Coculture Techniques; Drug Resistance, Multiple, Bacterial; Fibroblasts (microbiology); Gene Expression Profiling; Host-Pathogen Interactions; Humans; Microbial Interactions; Molecular Sequence Annotation; Probiotics; Virulence; Whole Genome Sequencing

PubMed ID

29872152

Recommended Citation

Chan, A. P., Choi, Y., Brinkac, L. M., Krishnakumar, R., DePew, J., Kim, M., Hinkle, M. K., Lesho, E. P., & Fouts, D. E. (2018). Multidrug resistant pathogens respond differently to the presence of co-pathogen, commensal, probiotic and host cells. Scientific Reports, 8 (1), 8656. https://doi.org/10.1038/s41598-018-26738-1