MSI-1 combats drug-resistant S. aureus by affecting bacterial viability and inhibiting carotenoid pigment production

Ye, Xinyue; Huang, Ya; Zhou, Chenyu; Liu, Xiaoyun; Zhao, Wenxuan; Zhao, Xiurong; Xie, Xiaolin; Wang, Liping; Bai, Zhaoshi; Zhou, Changlin; Ma, Lingman

doi:10.1016/j.micres.2021.126909

Cited by 9 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, the molecular docking study performed herein validated terbinafine interaction with CrtN. Similarly, Ye et al [ 51 ] has reported that a novel cationic peptide MSI-1 significantly inhibited staphyloxanthin production through binding with CrtN without any change in the expression of crtM or crtN. The molecular docking results strongly indicate that terbinafine inhibitory activity on staphyloxanthin is likely to be due to direct interference with CrtN enzyme activity.…”

Section: Discussionsupporting

confidence: 67%

Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies

Askoura

Yousef

Mansour

et al. 2022

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

Background Antimicrobial resistance is growing substantially, which necessitates the search for novel therapeutic options. Terbinafine, an allylamine antifungal agent that exhibits a broad spectrum of activity and is used in the treatment of dermatophytosis, could be a possible option to disarm S. aureus virulence. Methods Terbinafine inhibitory effect on staphyloxanthin was characterized by quantitative measurement of staphyloxanthin intermediates and molecular docking. The effect of terbinafine on S. aureus stress survival was characterized by viable counting. The anti-biofilm activity of terbinafine on S. aureus was assessed by the crystal violet assay and microscopy. Changes in S. aureus membrane following treatment with terbinafine were determined using Fourier transform infrared (FTIR) analysis. The synergistic action of terbinafine in combination with conventional antibiotics was characterized using the checkerboard assay. qRT-PCR was used to evaluate the impact of terbinafine on S. aureus gene expression. The influence of terbinafine on S. aureus pathogenesis was investigated in mice infection model. Results Terbinafine inhibits staphyloxanthin biosynthesis through targeting dehydrosqualene desaturase (CrtN). Docking analysis of terbinafine against the predicted active site of CrtN reveals a binding energy of − 9.579 kcal/mol exemplified by the formation of H-bonds, H-arene bonds, and hydrophobic/hydrophilic interactions with the conserved amino acids of the receptor pocket. Terbinafine treated S. aureus was more susceptible to both oxidative and acid stress as well as human blood killing as compared to untreated cells. Targeting staphyloxanthin by terbinafine rendered S. aureus more sensitive to membrane acting antibiotics. Terbinafine interfered with S. aureus biofilm formation through targeting cell autoaggregation, hydrophobicity, and exopolysaccharide production. Moreover, terbinafine demonstrated a synergistic interaction against S. aureus when combined with conventional antibiotics. Importantly, terbinafine attenuated S. aureus pathogenesis using mice infection model. qRT-PCR revealed that terbinafine repressed expression of the transcriptional regulators sigB, sarA, and msaB, as well as icaA in S. aureus. Conclusions Present findings strongly suggest that terbinafine could be used safely and efficiently as an anti-virulent agent to combat S. aureus infections.

show abstract

Section: Discussionsupporting

confidence: 67%

Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies

Askoura

Yousef

Mansour

et al. 2022

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

show abstract

“…Surprisingly, K122 remarkably promoted wound healing and reduced damage to skin tissues (Figure E). According to the histopathological examination, there were a large number of necrotic areas both on the skin surface and in the deep tissues accompanied by severe inflammatory cell infiltration and edema in model mice . However, in the treatment groups, especially the 1 and 4 mg/kg K122 groups, the number of inflammatory cells decreased, and only slight edema and ulcers could be observed in the skin tissues (Figure F).…”

Section: Resultsmentioning

confidence: 99%

“…According to the histopathological examination, there were a large number of necrotic areas both on the skin surface and in the deep tissues accompanied by severe inflammatory cell infiltration and edema in model mice. 20 However, in the treatment groups, especially the 1 and 4 mg/kg K122 groups, the number of inflammatory cells decreased, and only slight edema and ulcers could be observed in the skin tissues (Figure 9F). Taken together, K122 significantly reduced bacterial loads and inflammatory responses, thereby promoting wound healing.…”

Section: Design and Characterization Of The Sulfono-γ-aapeptidesmentioning

confidence: 99%

Novel Feleucin-K3-Derived Peptides Modified with Sulfono-γ-AA Building Blocks Targeting Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus Infections

et al. 2022

View full text Add to dashboard Cite

The prevalence of multidrug-resistant bacterial infections has led to dramatically increased morbidity and mortality. Antimicrobial peptides (AMPs) have great potential as new therapeutic agents to reverse this dangerous trend. Herein, a series of novel AMP Feleucin-K3 analogues modified with unnatural peptidomimetic sulfono-γ-AA building blocks were designed and synthesized. The structure–activity, structure–toxicity, and structure–stability relationships were investigated to discover the optimal antimicrobial candidates. Among them, K122 exhibited potent and broad-spectrum antimicrobial activity and high selectivity. K122 had a rapid bactericidal effect and a low tendency to induce resistance. Surprisingly, K122 showed excellent effectiveness against bacterial pneumonia. For biofilm and local skin infections, K122 significantly decreased the bacterial load and improved tissue injury at a dose of only 0.25 mg/kg, which was 160 times lower than the concentration deemed to be safe for local dermal applications. In summary, K122 is an outstanding candidate for the treatment of multidrug-resistant bacteria and biofilm infections.

show abstract

“…There are currently many studies exploring the anti-virulence and anti-biofilm strategies toward bacteria ( Imchen et al, 2022 ; Law and Tan, 2022 ). Findings show that some substances including cationic surfactants such as benzalkonium chloride ( Park and Yoon, 2023 ), chemicals such as Rhein ( Folliero et al, 2022 ) and 2,6-Di-tert-butyl-4-methylphenol ( Santhakumari et al, 2018 ), peptides such as MSI-I ( Ye et al, 2021 ) and PV-Q5 ( Dai et al, 2023 ), and traditional chinese medicine such as gingerol ( Shukla et al, 2021 ) and Ulva fasciata ( Qiao et al, 2021 ) possess anti-virulence and/or anti-biofilm activity. Compared to antibiotics such as chloramphenicol, these substances have obvious advantages, such as less susceptibility to bacterial resistance.…”

Section: Discussionmentioning

confidence: 99%

Effect of sublethal dose of chloramphenicol on biofilm formation and virulence in Vibrio parahaemolyticus

Zhang,

Cai,

Luo

et al. 2023

Front. Microbiol.

View full text Add to dashboard Cite

Vibrio parahaemolyticus isolates are generally very sensitive to chloramphenicol. However, it is usually necessary to transfer a plasmid carrying a chloramphenicol resistance gene into V. parahaemolyticus to investigate the function of a specific gene, and the effects of chloramphenicol on bacterial physiology have not been investigated. In this work, the effects of sublethal dose of chloramphenicol on V. parahaemolyticus were investigated by combined utilization of various phenotypic assays and RNA sequencing (RNA-seq). The results showed that the growth rate, biofilm formation capcity, c-di-GMP synthesis, motility, cytoxicity and adherence activity of V. parahaemolyticus were remarkably downregulated by the sublethal dose of chloramphenicol. The RNA-seq data revealed that the expression levels of 650 genes were significantly differentially expressed in the response to chloramphenicol stress, including antibiotic resistance genes, major virulence genes, biofilm-associated genes and putative regulatory genes. Majority of genes involved in the synthesis of polar flagellum, exopolysaccharide (EPS), mannose-sensitive haemagglutinin type IV pilus (MSHA), type III secretion systems (T3SS1 and T3SS2) and type VI secretion system 2 (T6SS2) were downregulated by the sublethal dose of chloramphenicol. Five putative c-di-GMP metabolism genes were significantly differentially expressed, which may be the reason for the decrease in intracellular c-di-GMP levels in the response of chloramphenicol stress. In addition, 23 genes encoding putative regulators were also significantly differentially expressed, suggesting that these regulators may be involved in the resistance of V. parahaemolyticus to chloramphenicol stress. This work helps us to understand how chloramphenicol effect on the physiology of V. parahaemolyticus.

show abstract

MSI-1 combats drug-resistant S. aureus by affecting bacterial viability and inhibiting carotenoid pigment production

Cited by 9 publications

References 31 publications

Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies

Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies

Novel Feleucin-K3-Derived Peptides Modified with Sulfono-γ-AA Building Blocks Targeting Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus Infections

Effect of sublethal dose of chloramphenicol on biofilm formation and virulence in Vibrio parahaemolyticus

Contact Info

Product

Resources

About