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Article

Different Modulatory Effects of Four Methicillin-Resistant Staphylococcus aureus Clones on MG-63 Osteoblast-Like Cells

1
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95125 Catania, Italy
2
Oasi Research Institute-IRCCS, Via Conte Ruggero, 73, 94018 Troina, Italy
3
Department of Drug Sciences, University of Catania, 95125 Catania, Italy
*
Author to whom correspondence should be addressed.
Consider that the first three should be regarded as joint first authors.
Biomolecules 2021, 11(1), 72; https://doi.org/10.3390/biom11010072
Received: 26 October 2020 / Revised: 30 November 2020 / Accepted: 29 December 2020 / Published: 7 January 2021
Staphylococcus aureus is a Gram-positive bacterium responsible for a variety of mild to life-threatening infections including bone infections such as osteomyelitis. This bacterium is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study, four different S. aureus strains, namely, 2SA-ST239-III (ST239), 5SA-ST5-II (ST5), 10SA-ST228-I (ST228), and 14SA-ST22-IVh (ST22), were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 (ST30) was used as control strain. Despite being proven that ST30, ST239, and ST22 have a similar ability to internalize and persist in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the observed decrease in cell viability was due to the different behavior of the considered strains, rather than the number of intracellular bacteria. We focused our attention on different biochemical cell functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show the following: (1) ST30 and ST239 were the only two clones able to persist and maintain their number in the hostile environment of the cell during the entire period of infection; (2) ST239 was the only clone able to significantly increase gene expression (3 and 24 h post-infection (p.i.)) and protein secretion (24 h p.i.) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; (3) the same clone determined a significant up-regulation of the transforming growth factorbeta 1 (TGF-β1) and of the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h p.i.; and (4) neither the MSSA nor the four methicillin-resistant S. aureus (MRSA) strains induced oxidative stress phenomena in MG-63 cells, although a high degree of variability was observed for the different clones with regard to the expression pattern of nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation. Our results may pave the way for an approach to S. aureus-induced damage, moving towards individualized therapeutic strategies that take into account the differences between MSSA and MRSA as well as the distinctive features of the different clones. This approach is based on a change of paradigm in antibiotic therapy involving a case-based use of molecules able to counteract pro-inflammatory cytokines activity such as selective cytokine signaling inhibitors (IL-6, TNF-α). View Full-Text
Keywords: Staphylococcus aureus; osteoblast-like cells; internalization; inflammation; immune system; eukaryotic host­–pathogen interaction; cytokines Staphylococcus aureus; osteoblast-like cells; internalization; inflammation; immune system; eukaryotic host­–pathogen interaction; cytokines
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MDPI and ACS Style

Musso, N.; Caruso, G.; Bongiorno, D.; Grasso, M.; Bivona, D.A.; Campanile, F.; Caraci, F.; Stefani, S. Different Modulatory Effects of Four Methicillin-Resistant Staphylococcus aureus Clones on MG-63 Osteoblast-Like Cells. Biomolecules 2021, 11, 72. https://doi.org/10.3390/biom11010072

AMA Style

Musso N, Caruso G, Bongiorno D, Grasso M, Bivona DA, Campanile F, Caraci F, Stefani S. Different Modulatory Effects of Four Methicillin-Resistant Staphylococcus aureus Clones on MG-63 Osteoblast-Like Cells. Biomolecules. 2021; 11(1):72. https://doi.org/10.3390/biom11010072

Chicago/Turabian Style

Musso, Nicolò, Giuseppe Caruso, Dafne Bongiorno, Margherita Grasso, Dalida A. Bivona, Floriana Campanile, Filippo Caraci, and Stefania Stefani. 2021. "Different Modulatory Effects of Four Methicillin-Resistant Staphylococcus aureus Clones on MG-63 Osteoblast-Like Cells" Biomolecules 11, no. 1: 72. https://doi.org/10.3390/biom11010072

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