Staphyloxanthin as a Potential Novel Target for Deciphering Promising Anti-Staphylococcus aureus Agents

Elmesseri, Rana A.; Saleh, Sarra E.; Elsherif, Heba M.; Yahia, I.S.; Aboshanab, Khaled M.

doi:10.3390/antibiotics11030298

Cited by 28 publications

(17 citation statements)

References 83 publications

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“…Furthermore, the obtained metagenome sequence was analyzed using DeepBGC software to detect the presence of secondary metabolite biosynthetic gene clusters as previously described (Hannigan et al 2019 ) Our results showed the presence of the biosynthetic gene cluster of two important active metabolites namely, bacillibactin (broad-spectrum antibacterial activity) (May et al 2001 ) and ectoine (osmolyte substance) (Peters et al 1990 ). The action of action is favorable for bacterial growth under extremely unfavorable condition like high salt concentration and accordingly, it can act as a new target for the development of antibacterial agents like the natural antioxidant staphyloxanthin produced by Staphylococcus aureus (Elmesseri et al 2022 ). It was previously reported that the bacillibactin class of antibiotics was isolated from marine Bacillus species and biochemically identified to have a promising broad-spectrum antibacterial activity (Chakraborty et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Eltokhy,

Saad,

Eltayeb

et al. 2024

AMB Expr

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Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.

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Section: Discussionmentioning

confidence: 99%

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Eltokhy,

Saad,

Eltayeb

et al. 2024

AMB Expr

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“…Previous studies have already shown the activity of 1,4-NQs for the inhibition of staphyloxanthin synthesis, indicating a promising approach to deal with the virulence of S. aureus strains [86–88].…”

Section: Discussionmentioning

confidence: 99%

Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms

Leitão,

Ferreira,

Gurgel do Amaral Valente Sá

et al. 2023

Journal of Medical Microbiology

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Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml−1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.

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“…Targeting virulence factor staphyloxanthin is one of the alternative therapeutic strategies to control S. aureus infection ( Xue et al., 2019 ; Ni et al., 2020 ; Elmesseri et al., 2022 ). In all experiments, cells treated with SYG-180-2-2 appeared white in color, which was significantly different from the golden yellow colored control cells.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule compound SYG-180-2-2 attenuates Staphylococcus aureus virulence by inhibiting hemolysin and staphyloxanthin production

Rao

Xu²,

Shen³

et al. 2022

Front. Cell. Infect. Microbiol.

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Multi-drug resistant Staphylococcus aureus infection is still a serious threat to global health. Therefore, there is an urgent need to develop new antibacterial agents based on virulence factor therapy to overcome drug resistance. Previously, we synthesized SYG-180-2-2 (C21H16N2OSe), an effective small molecule compound against biofilm. The aim of this study was to investigate the anti-virulence efficacy of SYG-180-2-2 against Staphylococcus aureus. MIC results demonstrated no apparent antibacterial activity of the SYG-180-2-2. The growth curve assay showed that SYG-180-2-2 had nonlethal effect on S. aureus. Besides, SYG-180-2-2 strongly inhibited the hemolytic activity and staphyloxanthin synthesis in S. aureus. Inhibition of staphyloxanthin by SYG-180-2-2 enhanced the sensitivity of S. aureus to oxidants and human whole blood. In addition, SYG-180-2-2 significantly decreased the expression of saeR-mediated hemolytic gene hlb and staphyloxanthin-related crtM, crtN and sigB genes by quantitative polymerase chain reaction (qPCR). Meanwhile, the expression of oxidative stress-related genes sodA, sodM and katA also decreased. Galleria Mellonella assay revealed that SYG-180-2-2 was not toxic to larvae. Further, the larvae infection model showed that the virulence of bacteria was significantly reduced after 4 μg/mL SYG-180-2-2 treatment. SYG-180-2-2 also reduced skin abscess formation in mice by reducing bacterial burden and subcutaneous inflammation. In conclusion, SYG-180-2-2 might be a promising agent to attenuate the virulence of S. aureus by targeting genes associated with hemolytic activity and staphyloxanthin synthesis.

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Staphyloxanthin as a Potential Novel Target for Deciphering Promising Anti-Staphylococcus aureus Agents

Cited by 28 publications

References 83 publications

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms

Small-molecule compound SYG-180-2-2 attenuates Staphylococcus aureus virulence by inhibiting hemolysin and staphyloxanthin production

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