Human skin microbiota-friendly lysostaphin

Bonar, Emilia; Bukowski, Michal; Chlebicka, Kinga; Madry, Anna; Bereznicka, Anna; Kosecka-Strojek, Maja; Dubin, Grzegorz; Międzobrodzki, Jacek; Mak, Paweł; Władyka, Benedykt

doi:10.1016/j.ijbiomac.2021.04.154

Cited by 11 publications

(6 citation statements)

References 56 publications

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“…A common bacterial NAD + -dependent enzyme responsible for the lysine desuccinylation is the sirtuin-like protein CobB [17]. In fact, the Staphylococcus pseudintermedius genome contains NAD + -dependent protein deacylase [45].…”

Section: Bacsp222 Succinylation Is a Nonenzymatic Process Dependent On Suc-coa And Ph Whereas Desuccinylation Requires Nad + And Cytoplasmentioning

confidence: 99%

Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222

Śmiałek

Nowakowski

Bzowska

et al. 2021

IJMS

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BacSp222 is a multifunctional peptide produced by Staphylococcus pseudintermedius 222. This 50-amino acid long peptide belongs to subclass IId of bacteriocins and forms a four-helix bundle molecule. In addition to bactericidal functions, BacSp222 possesses also features of a virulence factor, manifested in immunomodulatory and cytotoxic activities toward eukaryotic cells. In the present study, we demonstrate that BacSp222 is produced in several post-translationally modified forms, succinylated at the ε-amino group of lysine residues. Such modifications have not been previously described for any bacteriocins. NMR and circular dichroism spectroscopy studies have shown that the modifications do not alter the spatial structure of the peptide. At the same time, succinylation significantly diminishes its bactericidal and cytotoxic potential. We demonstrate that the modification of the bacteriocin is an effect of non-enzymatic reaction with a highly reactive intracellular metabolite, i.e., succinyl-coenzyme A. The production of succinylated forms of the bacteriocin depends on environmental factors and on the access of bacteria to nutrients. Our study indicates that the production of succinylated forms of bacteriocin occurs in response to the changing environment, protects producer cells against the autotoxicity of the excreted peptide, and limits the pathogenicity of the strain.

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Section: Bacsp222 Succinylation Is a Nonenzymatic Process Dependent On Suc-coa And Ph Whereas Desuccinylation Requires Nad + And Cytoplasmentioning

confidence: 99%

Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222

Śmiałek

Nowakowski

Bzowska

et al. 2021

IJMS

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“…For example, bacteriocins produced by staphylococci – widespread residents and opportunistic pathogens of the skin and mucous membranes of humans and many animals – comprise four groups: 1) lantibiotics (small single-chain posttranslationally modified peptides, such as epidermin, gallidermin, or BacCH91), 2) unmodified single-chain peptides (such as aureocin A53, epidermicin NI01, and BacSp222), 3) unmodified multi-chain peptides (such as staphylococcin C55 and aureocin A70), and 4) bacteriolytic enzymes (such as lysostaphins LSs and LSp222 as well as endopeptidase ALE-1). 10 , 11 Among these factors, one staphylococcal bacteriocin has attracted our special attention in recent years, namely the BacSp222 peptide, as this interesting molecule combines the features of a virulence factor, a bacteriocin, and a molecule that modulates the host inflammatory reaction.…”

Section: Introductionmentioning

confidence: 99%

Bacteriocin BacSp222 and Its Succinylated Forms Exhibit Proinflammatory Activities Toward Innate Immune Cells 

Śmiałek¹,

Bzowska²,

Hinz³

et al. 2022

JIR

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Purpose The zoonotic opportunistic pathogen Staphylococcus pseudintermedius 222 produces BacSp222 – an atypical peptide exhibiting the features of a bacteriocin, a virulence factor, and a molecule modulating the host inflammatory reaction. The peptide is secreted in an unmodified form and, additionally, two forms modified posttranslationally by succinylation. This study is a comprehensive report focusing on the proinflammatory properties of such molecules. Methods The study was performed on mouse monocyte/macrophage-like and endothelial cell lines as well as human neutrophils. The following peptides were studied: BacSp222, its succinylated forms, the form deprived of formylated methionine, and a reference bacteriocin – nisin. The measurements of the nitric oxide (NO) level, induced NO synthase (iNOS) expression, the profile of secreted cytokines, NF-kappa-B activation, reactive oxygen species (ROS) biosynthesis, and the formation of extracellular traps were conducted to evaluate the proinflammatory activity of the studied peptides. Results BacSp222 and its succinylated forms effectively induced NO production and iNOS expression when combined with IFN-gamma in macrophage-like cells. All natural BacSp222 forms used alone or with IFN-gamma stimulated the production of TNF-alpha, MCP-1, and IL-1-alpha, while the co-stimulation with IFN-gamma increased IL-10 and IL-27. Upregulated TNF-alpha secretion observed after BacSp222 exposition resulted from increased expression but not from membrane TNF-alpha proteolysis. In neutrophils, all forms of bacteriocin upregulated IL-8, but did not induce ROS production or NETs formation. In all experiments, the activities of deformylated bacteriocin were lower or unequivocal in comparison to other forms of the peptide. Conclusion All naturally secreted forms of BacSp222 exhibit proinflammatory activity against monocyte-macrophage cells and neutrophils, confirming that the biological role of BacSp222 goes beyond bactericidal and cytotoxic effects. The atypical posttranslational modification (succinylation) does not diminish its immunomodulatory activity in contrast to the lower antibacterial potential or cytotoxicity of such modified form established in previous studies.

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“…Recognizing these bacteria as potential sources of contamination is crucial for implementing targeted infection control measures [49,50]. Staphylococcus species, including S. epidermidis, S. saprophyticus, S. arlettae, and S. warneri, are associated with the human skin microbiota and may be introduced into the dental environment during patient interactions [51]. Identifying and studying these bacterial species is essential because they may serve as potential sources of contamination and contributors to the risk of infections in dental settings.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Hydrogen Peroxide (H2O2) Fumigation on Bacterial Levels in Dental Office Environments: A Randomized Clinical Trial Investigation

Matys,

Gedrange,

Dominiak

et al. 2023

JCM

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Background: Fumigation with hydrogen peroxide has proven to be a highly effective approach to maintaining biological safety within dental offices. The main purpose of this research was to investigate the efficacy of hydrogen peroxide (H2O2) fumigation in reducing bacterial levels in dental office environments. Methods: The study involved 30 participants diagnosed with moderate caries decay (ICDAS 3 and 4) in their mandibular molars. Sixty Petri dishes (two per patient) with Columbia Agar and 5% Sheep Blood were opened at the beginning of the caries treatment. After the completion of caries treatment and tooth restoration, 30 plates (G1 group) were closed. Following this, a 20 min fumigation procedure with 6% hydrogen peroxide biosanitizer using a compressed air device was conducted. After the fumigation, the remaining plates were closed (G2 group). The total number of bacteria CFUs (colony-forming units) in the dental office air was determined using the Koch sedimentation method. Results: The total bacterial colony (TBC) level, measured in cfu/m3, demonstrated a significant decrease in the number of bacteria following room environment fumigation (163.1 ± 145.7; G2 group) compared to non-fumigated samples (817.2 ± 208.2; G1 group) (p < 0.001). The predominant bacteria observed in the microbiological plates before fumigation were Micrococcus and Bacillus species, found in 80% (24/30) and 60% (18/30) of the plates, respectively. Application of H2O2 room fumigation resulted in a significant reduction in bacterial numbers: 79.2% (5/30) for Micrococcus species (p < 0.001), 83.3% (3/30) for Bacillus species (p < 0.001), and 100% (0/30) for Staphylococcus arlettae (p < 0.05). Conclusion: Fumigation with 6% H2O2 is an effective method for reducing bacterial counts in a dental office environment.

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Human skin microbiota-friendly lysostaphin

Cited by 11 publications

References 56 publications

Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222

Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222

Bacteriocin BacSp222 and Its Succinylated Forms Exhibit Proinflammatory Activities Toward Innate Immune Cells

The Impact of Hydrogen Peroxide (H2O2) Fumigation on Bacterial Levels in Dental Office Environments: A Randomized Clinical Trial Investigation

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