Chinese herb medicine against Sortase A catalyzed transformations, a key role in gram-positive bacterial infection progress

Abstract

Many Gram-positive bacteria can anchor their surface proteins to the cell wall peptidoglycan covalently by a common mechanism with Sortase A (SrtA), thus escaping from the host's identification of immune cells. SrtA can complete this anchoring process by cleaving LPXTG motif conserved among these surface proteins and thus these proteins anchor on the cell wall. Moreover, those SrtA mutants lose this capability to anchor these relative proteins, with these bacteria no longer infectious. Therefore, SrtA inhibitors can be promising anti-infective agents to cure bacterial infections. Chinese herb medicines (CHMs) (chosen from Science Citation Index) have exhibited inhibition on SrtA of Gram-positive pathogens irreversibly or reversibly. In general, CHMs are likely to have important long-term impact as new antibacterial compounds and sought after by academia and the pharmaceutical industry. This review mainly focuses on SrtA inhibitors from CHMs and the potential inhibiting mechanism related to chemical structures of compounds in CHMs.

New 2-Phenylthiazoles as Potential Sortase A Inhibitors: Synthesis, Biological Evaluation and Molecular Docking

“…Due to the structural similarity of the active site of different sortases A, it is assumed that this catalytic process is similar for most sortases A. A phylogenetic analysis of SrtA reveals that these enzymes are closely related with various degrees of homology [ 17 , 34 ].…”

“…In the same time, the fact that these enzymes are found in the membrane/cell-wall implies that inhibitors do not have to penetrate inside the bacterial cell, which diminishes the pharmacokinetic requirements for a new inhibitor. Another potential benefit of Sortase A inhibitors would be the fact that they will act only by reducing virulence and biofilm formation, thus exerting no selective pressure that could eventually lead to development of resistant bacteria strains [ 14 , 16 , 17 ].…”

Comparison of the Gut Microbiota Between Pulsatilla Decoction and Levofloxacin Hydrochloride Therapy on Escherichia coli Infection

“…Both Chinese herbs and the gut microbiota had the regulation of innate immunity (Wójcik et al, 2009;Wang et al, 2019). Therefore, Chinese herbs rarely has a direct antibacterial ability, but it can rely on inhibiting bacterial growth proteins to inhibit infection (Si et al, 2016) or enhance the regulatory factors that promote innate immunity to achieve antibacterial effect (Ma et al, 2013(Ma et al, , 2018Si et al, 2016;Wang et al, 2016;Yang et al, 2018;Pascale et al, 2019). Consisting with the long-term research of our labs that the integrity of barrier cells such as epithelial cells and endothelial cells contributed to the bactericidal function of immune cells such as neutrophils (Liu et al, 2016).…”

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of Staphylococcus aureus

“…Since S. aureus α-toxin can even cause the infection of Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae (Cohen et al, 2016), the drug discovery for antitoxins is worth researching. Although the activities of the direct antibacterial activation in natural herbs are mostly weaker than that of antibiotics (Si et al, 2016; FIGURE 1 | Paeoniae Radix aqueous extract and the active ingredients. Paeoniae Radix aqueous extract (PRAE) were prepared from the traditional Chinese herb Peony root.…”