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. 2021 Nov;10(6):e1256.
doi: 10.1002/mbo3.1256.

Transcriptomic analysis of Streptococcus agalactiae periprosthetic joint infection

Hye-Kyung Cho  1 , Thao Masters  1 , Kerryl E Greenwood-Quaintance  1 , Stephen Johnson  2 , Patricio R Jeraldo  3   4 , Nicholas Chia  3   4 , Meng Pu  5 , Matthew P Abdel  6 , Robin Patel  1   7
Affiliations

Transcriptomic analysis of Streptococcus agalactiae periprosthetic joint infection

Hye-Kyung Cho et al. Microbiologyopen. 2021 Nov.

Abstract

Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA-seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding β-hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.

Keywords: RNA-seq; Streptococcus agalactiae; prosthesis-related infections; transcriptome.

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Conflict of interest statement

Dr. Patel reports grants from ContraFect, TenNor Therapeutics Ltd, Hylomorph, BioFire, and Shionogi. Dr. Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus, Mammoth Biosciences, and Qvella; monies are paid to Mayo Clinic. Dr. Patel is also a consultant to Netflix. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on an anti‐biofilm substance issued, and a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic. Dr. Patel receives an editor's stipend from the Infectious Diseases Society of America, and honoraria from the National Board of Medical Examiners, the Infectious Diseases Board Review Course, and UpToDate Inc. All other authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Functional enrichment of outlier Streptococcus agalactiae genes in periprosthetic joint infection sonicate fluid compared to NEM316 grown in vitro. Genes with |z| > 3 were considered outliers. The ratio of enrichment was calculated as the % of genes of a given functional category in the increased or decreased expressed RNA‐seq data set/% of genes assigned to the functional category in the S. agalactiae genome. Ribosomal protein, rRNA, and tRNA genes were removed. *Significant enrichment amongst genes increased; †significant enrichment amongst genes decreased in sonicate fluid, with p < 0.05 (Fisher's exact test). rRNA, ribosomal RNA; tRNA, transfer RNA
Figure 2
Figure 2
(a) Expression levels of genes involved in bacterial adhesion in sonicate fluid of four periprosthetic joint infection (PJI) subjects compared to NEM316 in vitro. *Upregulated outliers in sonicate fluid; †downregulated outliers in sonicate fluid. (b) Expression levels of invasin and immune evasin genes in sonicate fluid of four PJI subjects compared to NEM316 in vitro. *Upregulated outliers in sonicate fluid; †downregulated outliers in sonicate fluid
Figure A1
Figure A1
Phylogenic tree of the cultured isolates and Streptococcus agalactiae NEM316 and 2603V/R
Figure A2
Figure A2
Protein structure homology model of sag1514–1518 (a–e, respectively) produced by Phyre2. The predicted protein from sag1514–1518 is shown in blue with the template protein (Table A3) shown in yellow
See this image and copyright information in PMC

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