The study of honokiol as a natural product-based antimicrobial agent and its potential interaction with FtsZ protein.

Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used ß-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant S. aureus strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The in vivo antibacterial activity of honokiol against S. aureus infection was also verified with a biological model of G. mellonella larvae. The in vivo results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with S. aureus. These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria.

Carvacrol inhibits bacterial polysaccharide intracellular adhesin synthesis and biofilm formation of mucoid Staphylococcus aureus: an in vitro and in vivo study.

Staphylococcus aureus (S. aureus) is one of the important human pathogens and causes both superficial and systemic infections. More importantly, the formation of S. aureus biofilms, a main cause of its pathogenicity and drug resistance, has been a critical challenge in clinical treatment. Carvacrol, a plant-based natural product, has gained great interest for therapeutic purposes due to its effective biological activity with low cytotoxicity. The present study aimed to investigate the effect of carvacrol on anti-biofilm activity. Growth curve analysis showed that applying a sub-inhibitory concentration of carvacrol (4 µg mL-1) was not lethal to S. aureus SYN; however, the inhibition rate of biofilm formation was as high as 63.6%, and the clearance rate of mature biofilms was as high as 30.7%. In addition, carvacrol effectively reduced the production of biofilm-associated extracellular polysaccharides and showed no effect on eDNA release. Furthermore, qPCR analysis revealed that carvacrol significantly down-regulated the expression of icaA, icaB, icaC, agrA, and sarA (P < 0.05). The in vivo efficacy of carvacrol against biofilm infection was further verified with a biological model of G. mellonella larvae. The results showed that carvacrol was non-toxic to the larvae and can effectively increase the survival rate of the larvae infected with S. aureus strain SYN.

Identification and Characterization of a Vancomycin Intermediate-Resistant Staphylococcus haemolyticus Isolated from Guangzhou, China.

Background: Staphylococcus haemolyticus is an opportunistic pathogen that belongs to coagulase-negative Staphylococci (CoNS). Increasing infection and multi-drug resistance cases caused by this strain have been reported and thus it poses a great health threat. Methods: The third-generation sequencing technology was performed on a S. haemolyticus SH-1 isolated from a clinical sample to analyze the drug resistance genes, which included vancomycin resistance related genes. In addition, antimicrobial susceptibility tests, transmission electron microscopy and Triton X-100 stimulated autolysis were conducted to understand its biological characteristics. Results: The study shows that this clinical isolate is a vancomycin intermediate-resistant strain. Genome comparison also revealed that WalK(N70K) and WalK(R280Q) mutations may contribute to the vancomycin resistant phenotype. Besides, S. haemolyticus SH-1 exhibit common features of thicker cell wall and decreased autolytic activity. Conclusion: S. haemolyticus SH-1 with WalKR mutations shows typical characteristics of vancomycin resistant strains. Combining the genome features and biological properties, our findings may provide important information for the understanding of the molecular mechanism of S. haemolyticus to vancomycin intermediate-resistance.

A Review of Biofilm Formation of Staphylococcus aureus and Its Regulation Mechanism.

Bacteria can form biofilms in natural and clinical environments on both biotic and abiotic surfaces. The bacterial aggregates embedded in biofilms are formed by their own produced extracellular matrix. Staphylococcus aureus (S. aureus) is one of the most common pathogens of biofilm infections. The formation of biofilm can protect bacteria from being attacked by the host immune system and antibiotics and thus bacteria can be persistent against external challenges. Therefore, clinical treatments for biofilm infections are currently encountering difficulty. To address this critical challenge, a new and effective treatment method needs to be developed. A comprehensive understanding of bacterial biofilm formation and regulation mechanisms may provide meaningful insights against antibiotic resistance due to bacterial biofilms. In this review, we discuss an overview of S. aureus biofilms including the formation process, structural and functional properties of biofilm matrix, and the mechanism regulating biofilm formation.