Thermonuclease (Nuc1) (Nuc1)

Thermonuclease, commonly referred to as Nuc1 or micrococcal nuclease, is a major extracellular enzyme and critical virulence factor secreted by Staphylococcus aureus [6, 12]. Its primary biological function is the non-specific hydrolysis of both DNA and RNA into mono- and oligonucleotides [9, 10]. In the host environment, Nuc1 facilitates immune evasion by degrading the DNA backbone of neutrophil extracellular traps (NETs), which are web-like structures deployed by the host to entrap and kill pathogens [6, 21]. By destroying these traps, Nuc1 enables the bacterium to escape host killing and contributes to the persistence and dissemination of the infection [9, 10]. Additionally, Nuc1 plays a role in the modulation of biofilm formation and dispersal by regulating the levels of extracellular DNA (eDNA) within the biofilm matrix [8, 14]. From a therapeutic perspective, Nuc1 is an attractive anti-virulence target. Inhibition of its production or activity can disarm the bacteria and enhance host clearance without the selective pressure of traditional bactericidal antibiotics [6, 10]. Clinical agents such as clindamycin have been shown to downregulate nuc1 transcription at sub-inhibitory concentrations, while intravenous immunoglobulin (IVIG) contains neutralizing antibodies that can directly inhibit the enzyme's activity [6, 10]. Furthermore, the high conservation of the nuc gene across S. aureus strains makes it a definitive biomarker for rapid molecular diagnosis in clinical settings [1, 18].

Other names

Staphylococcal nucleaseMicrococcal nucleaseSNaseThermostable nucleasenuc gene productNuclease A

Inhibition of thermonuclease expression or enzymatic activity prevents the degradation of host-derived neutrophil extracellular traps (NETs), thereby restoring the ability of the innate immune system to entrap and clear the bacterial pathogen.