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Lycopene attenuates Staphylococcus aureus-induced inflammation via inhibiting alpha-Hemolysin

Lycopene attenuates #Staphylococcus aureus-induced #inflammation via inhibiting α-Hemolysin expression


The purpose of this study was to explore the effect of Lycopene in Staphylococcus aureus (S. aureus) (USA 300)-induced inflammation and to elucidate the potential mechanism of its action. The direct effect of Lycopene on S. aureus USA300 growth was determined via growth curves assay, and α-Hemolysin (Hla) release of S. aureus USA300 using hemolysis assay. Furthermore, S. aureus USA300 infected mouse model was established by intranasally infection using bacterial suspension. Histological evaluation of lung tissue after infection was carried out using H&E staining. The lungs edema was estimated using wet/dry ratio. The concentrations of cytokines in lung tissues homogenate were detected using the commercial enzyme-linked immunosorbent assay kit. It was shown that Lycopene inhibited Hla hemolytic activity and decreased expression of Hla and regulatory RNAIII Lycopene treatment protected A549 cells from S. aureus USA300 induced injury and acute lung inflammation. Inflammatory cytokines were also down-regulated by Lycopene treatment in the lung tissues of S. aureus USA300 infected mice. In conclusion, Lycopene restrains S. aureus-induced inflammation via inhibiting α-Hemolysin expression.

1. Introduction

Staphylococcus aureus (S. aureus) remains one of the major reasons for severe infections, such as sepsis, endocarditis pneumonia, osteomyelitis, and keratitis in humans [1, 2]. S. aureus is commonly found in natural environments and even in 30% of healthy people, which makes this pathogen to be a threat for public health worldwide [3]. In the last 30 years, drug-resistant pathogen methicillin-resistant S. aureus emerges with elevated infectivity and enhanced virulence, while the new discovery for antimicrobial agent decreased, which cooperatively boosts the seriousness of S. aureus infection [4, 5]. The methicillin-resistant S. aureus infection with high variable virulence factors distribution is increasing, especially in community-acquired infections [6]. In the United States alone, S. aureus infection leads to around 12,000 deaths, $3.5 billion charges and 2.7 million days stay in hospital per year [7]. In the clinic, the last option for methicillin-resistant S. aureus infection is vancomycin application. However, the efficiency of vancomycin is decreasing in the past years, suggesting that methicillin-resistant S. aureus infection might be an incurable disease in the future [8, 9]. All the facts indicate that it is urgent to search the effective strategies for S. aureus infections.

Lycopene is an aliphatic carotenoid, commonly presents in tomato and tomato-associated products [10, 11]. It deactivates reactive oxygen species (ROS) and removes singlet oxygen 10 times as intense as alpha-tocopherol [13]. Based on the strong antioxidant property, Lycopene is widely used for anti-inflammation in various diseases, and the health benefit of Lycopene in protecting and treating diseases has been explored [14, 15]. However, the effect of Lycopene in S. aureus infection, especially methicillin-resistant S. aureus infection-induced inflammation remains unknown.

During S. aureus infection, α-Hemolysin (Hla) is involved in the activation of immune signaling. When coupling with other S. aureus-derived molecules, α-Hemolysin (Hla) could directly trigger inflammation by activating recognition receptors [16]. Moreover, Hla plays a significant role in S. aureus infection to lungs by mediating air-blood barrier damage [17].

This study was designed to explore the effect of Lycopene on the toxicity of methicillin-resistant S. aureus (USA 300) in A549 cell lines and USA 300 induced inflammation in animal models. The results indicated that Lycopene suppressed the hemolytic activity of α-Hemolysin (Hla) via regulating its regulatory factors. In A549 cells, Lycopene suppressed S. aureus USA300 induced cell death and lactate dehydrogenase (LDH) release. In the S. aureus USA300 infected mouse model, Lycopene treatment attenuates lung damage, inflammation, and inflammatory cytokine expression.

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