Hibifolin, a Natural Sortase A Inhibitor, Attenuates the Pathogenicity of Staphylococcus aureus and Enhances the Antibacterial Activity of Cefotaxime

Wu, Song; Wang, Li; Zhao, Yaohua; Lanzi, G.; Wang, Xingye; Zhang, Chi; Guan, Jiyu; Wang, Wei; Guo, Xuerui; Meng, Ying; Wang, Bingmei; Zhao, Yicheng

doi:10.1128/spectrum.00950-22

Cited by 14 publications

(12 citation statements)

References 45 publications

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“…Based on the obtained results, we suggested that the studied bioactive compounds could inhibit the activity of the SrtA enzyme by binding to its active site. Similar findings were demonstrated by another in silico study, which displayed that hibifolin attenuated the pathogenicity of S. aureus by inhibiting SrtA activity at free energy of binding equal to −6.8 Kcal/mol [ 58 ]. The interaction profiles representing the binding mode of the tested molecules against the selected bacterial virulence factors active sites are elucidated in Figure 3 , Figure 4 , Figure 5 and Figure 6 , and all the interaction details are summarized in Table 1 .…”

Section: Resultssupporting

confidence: 86%

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation

Akermi,

Chaari,

Elhadef

et al. 2024

Foods

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During the last few decades, there has existed an increased interest in and considerable consumer preference towards using natural and safe compounds derived from medicinal plants as alternatives to synthetic preservatives to combat microbial pathogenicity. In this regard, the present study investigated the possible synergistic interactions of the anti-foodborne bacterial capacity of linalool (L), eucalyptol (E), and camphor (C). The antibacterial synergistic effect was determined against Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica Typhimurium, and Escherichia coli. The optimal predicted mixture showed the highest antibacterial activity at 33.5%, 33.2%, and 33.4% of L, E, and C, respectively. Molecular docking simulations displayed that the studied monoterpenes have effective antibacterial inhibitory effects by impeding specific virulence factors such as sortase A, listeriolysin O, L, D-Transpeptidase, and polyphosphate kinase. The selected triple combination of L, E, and C was applied as a natural preservative in minced chicken breast meat. In this regard, 1 MIC (16 µg/mL), 1.5 MIC (24 µg/mL), and 2 MIC (32 µg/mL) of L. monocytogenes were used, and the microbiological, physicochemical, and sensory analyses were monitored for 14 days of storage at 4 °C. The L/E/C mixture at different levels could delay lipid and protein oxidation, inhibit the microorganisms, and maintain the sensory attributes. Additionally, by using chemometric tools, strong connections between physicochemical properties, microbiological parameters, and organoleptic attributes were established. Concisely, this research confers the importance of the use of blended monoterpenes and highlights their antibacterial mode of action, effectiveness, and synergistic effects as a powerful and safe bio-preservative formulation in chicken meat products.

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Section: Resultssupporting

confidence: 86%

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation

Akermi,

Chaari,

Elhadef

et al. 2024

Foods

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“…It attenuates the virulence of both MSSA and MRSA strains in vitro and in vivo. As with other sortase A inhibitors tested in murine models of S. aureus infections [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ], LPRDA may impact the development of novel antibacterial agents. The pure crystalline form of LPRDA is characterized by good solubility and tolerance to eukaryotic and bacterial cells at working concentrations.…”

Section: Discussionmentioning

confidence: 99%

Oligopeptide Sortase Inhibitor Modulates Staphylococcus aureus Cell Adhesion and Biofilm Formation

et al. 2022

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Prevention of bacterial adhesion is one of the most important antivirulence strategies for meeting the global challenge posed by antimicrobial resistance. We aimed to investigate the influence of a peptidic S. aureus sortase A inhibitor on bacterial adhesion to eukaryotic cells and biofilm formation as a potential method for reducing S. aureus virulence. The pentapeptide LPRDA was synthesized and characterized as a pure individual organic compound. Incubation of MSSA and MRSA strains with LPRDA induced a subsequent reduction in staphylococcal adhesion to Vero cells and biofilm formation, as visualized by microscopic and spectrophotometric methods, respectively. LPRDA did not have a cytotoxic effect on eukaryotic or bacterial cells. The pentapeptide LPRDA deserves further investigation using in vitro and in vivo models of Gram-positive bacteriemia as a potential antibacterial agent with an antiadhesive mechanism of action.

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“…Computational drug engineering, for instance, identified 3,6-disubstituted triazolothiadiazole as a potent inhibitor of sortase A that improved infection outcomes of lethal S. aureus bacteremia ( Table 1 ; Zhang et al, 2014 ). Further, compound library screening helped to isolate several natural products with sortase A-blocking and anti-infective properties ( Table 1 ; Song et al, 2022a , b ). Some of these agents even potentiated the efficacy of cell wall biosynthesis-targeting antibiotics during experimental pneumonia, presumably aiding in the design of poly-therapeutic approaches that may also encompass usage of allantodapsone, a prototype pan-inhibitor of staphylococcal adhesion to extracellular matrix proteins ( Prencipe et al, 2022 ), to combat complicated MRSA infections in the future ( Table 1 ; Song et al, 2022a , b ; Wang et al, 2022b ).…”

Section: Targeting Cell Surface Proteins and Sortase A To Improve ...mentioning

confidence: 99%

Functional diversity of staphylococcal surface proteins at the host-microbe interface

Schwermann

Winstel

2023

Front. Microbiol.

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Surface proteins of Gram-positive pathogens are key determinants of virulence that substantially shape host-microbe interactions. Specifically, these proteins mediate host invasion and pathogen transmission, drive the acquisition of heme-iron from hemoproteins, and subvert innate and adaptive immune cell responses to push bacterial survival and pathogenesis in a hostile environment. Herein, we briefly review and highlight the multi-facetted roles of cell wall-anchored proteins of multidrug-resistant Staphylococcus aureus, a common etiological agent of purulent skin and soft tissue infections as well as severe systemic diseases in humans. In particular, we focus on the functional diversity of staphylococcal surface proteins and discuss their impact on the variety of clinical manifestations of S. aureus infections. We also describe mechanistic and underlying principles of staphylococcal surface protein-mediated immune evasion and coupled strategies S. aureus utilizes to paralyze patrolling neutrophils, macrophages, and other immune cells. Ultimately, we provide a systematic overview of novel therapeutic concepts and anti-infective strategies that aim at neutralizing S. aureus surface proteins or sortases, the molecular catalysts of protein anchoring in Gram-positive bacteria.

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Hibifolin, a Natural Sortase A Inhibitor, Attenuates the Pathogenicity of Staphylococcus aureus and Enhances the Antibacterial Activity of Cefotaxime

Cited by 14 publications

References 45 publications

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation

Oligopeptide Sortase Inhibitor Modulates Staphylococcus aureus Cell Adhesion and Biofilm Formation

Functional diversity of staphylococcal surface proteins at the host-microbe interface

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