Staphylococcus aureus Toxins: From Their Pathogenic Roles to Anti-virulence Therapy Using Natural Products

Abstract

Staphylococcus aureus (S. aureus) produces a wide variety of toxins that cause various diseases in humans. S. aureus toxins are divided into three categories; (i) superantigens (SAgs) that interfere with receptor function and cause toxic shock syndrome (TSS) or staphylococcal food poisoning (SFP), (ii) exfoliative toxins (ETs) that destroy epidermal barrier functions and cause staphylococcal scalded skin syndrome (SSSS), and (iii) cytotoxins that cause cell lysis. Recently, anti-toxin neutralizing agents have been engineered and proven to be effective in preventing or treating staphylococcal diseases. However, neutralization of a single toxin may not sufficiently protect the host from S. aureus infection. Biofilm formation and the pathogenesis of S. aureus are closely associated with accessory gene regulator-quorum sensing (agr-QS) system that controls the expressions of many virulence factors including exotoxins. In addition to anti-toxin antibodies, indirect approaches involving targeting of the agr-QS system are considered a novel means of inhibiting the virulence of S. aureus and controlling various diseases caused by the pathogen. This review summarizes basic concepts of the pathogenic roles of S. aureus toxins, the molecular features of the agr-QS system, and of natural product-based anti-virulence therapies that target virulence, rather than growth.

Virulence Factor Genes and Antimicrobial Susceptibility of Staphylococcus aureus Strains Isolated from Blood and Chronic Wounds

“…The luk-F/S-PV gene is detected more often in SSTI isolates than in SAB isolates [ 15 , 26 , 32 , 45 , 46 , 47 , 48 ], which confirms our results. The incidence of luk-F/S-PV gene in this study, however, was not high (3.0%), unlike the results of other researchers, in which it reached about 80% [ 35 , 47 ].…”

“…Because many virulence factors are targets for the immune system, their downregulation or loss of agr-qs prevents further recruitment of phagocytes so is crucial for bacterial survival and long-term persistence in host cells/tissue. Strains isolated from chronic infections may also rewire their metabolism to promote biofilm production or may survive in a metabolically inactive state forming small-colony variants [ 31 , 32 , 33 ].…”

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

“…Natural product-based compounds that present anti-toxin properties correspond to a promising therapeutical approach to treat S. aureus infections [18]. A modified cyclodextrin compound, named IB201, is used to treat pneumonia.…”

“…However, these studies have not yet generated promising results due to toxicity and/or low bioavailability. New options are now under study with a focus on biological molecules or compounds to interfere with toxins or toxin-regulator genes, constituting a new generation of promising antistaphylococcal treatments [17][18][19][20][21].…”

Detection of Staphylococcus aureus and their toxin genes inhabit on the scorpions surface

“…Toxins of this bacterium play an important role in its pathogenesis. Recent studies, for instance, have shown an association between PVL (Panton Valentine Leukocidin) and methicillin-resistant strains of S. aureus, or the toxic shock syndrome toxin-1 gene produces a protein that causes systemic disease (Hennekinne et al 2012;Oliveira et al 2018;Kim 2019). The Exfoliative toxin is another important toxin of this bacterium that can cause complications such as staphylococcal scaly skin syndrome.…”