title: Arginine deiminase in Staphylococcus epidermidis functions to augment biofilm maturation through pH homeostasis.
abstract: Allelic replacement mutants were constructed within arginine deiminase (arcA1 and arcA2) to assess the function of the arginine deiminase (ADI) pathway in organic acid resistance and biofilm formation of Staphylococcus epidermidis 1457. A growth-dependent acidification assay (pH ∼5.0 to ∼5.2) determined that strain 1457 devoid of arginine deiminase activity (1457 ΔADI) was significantly less viable than the wild type following depletion of glucose and in the presence of arginine. However, no difference in viability was noted for individual 1457 ΔarcA1 (native) or ΔarcA2 (arginine catabolic mobile element [ACME]-derived) mutants, suggesting that the native and ACME-derived ADIs are compensatory in S. epidermidis. Furthermore, flow cytometry and electron paramagnetic resonance spectroscopy results suggested that organic acid stress resulted in oxidative stress that could be partially rescued by the iron chelator dipyridyl. Collectively, these results suggest that formation of hydroxyl radicals is partially responsible for cell death via organic acid stress and that ADI-derived ammonia functions to counteract this acid stress. Finally, static biofilm assays determined that viability, ammonia synthesis, and pH were reduced in strain 1457 ΔADI following 120 h of growth in comparison to strain 1457 and the arcA1 and arcA2 single mutants. It is hypothesized that ammonia synthesis via the ADI pathway is important to reduce pH stress in specific microniches that contain high concentrations of organic acids.
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Lindgren
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Thomas
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Olson
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Chaudhari
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Nuxoll
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Schaeffer
authors.affiliation: University of Nebraska Medical Center, Department of Orthopedic Surgery, Omaha, Nebraska, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Lindgren
authors.affiliation: University of Nebraska Medical Center, Department of Cellular and Integrative Physiology, Omaha, Nebraska, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.affiliation: University of Nebraska Medical Center, Department of Cellular and Integrative Physiology, Omaha, Nebraska, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Zimmerman
authors.affiliation: University of Rochester, Department of Microbiology and Immunology, Rochester, New York, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Dunman
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Bayles
authors.affiliation: University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA pfey@unmc.edu.
authors.forename: P D
authors.initials: PD
authors.lastname: Fey
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009876:Operon; D018384:Oxidative Stress; D013212:Staphylococcus epidermidis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D059467:Transcriptome
chemical_list: D006867:Hydrolases; C019723:arginine deiminase
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