The detrimental impact of extracellular bacterial proteases on wound healing

Abstract

In addition to clinical signs of infection (e.g. inflammation, purulence and pain), a microbial count of ≥10 colony-forming units/g has historically been used to define wound infection. However, it is increasingly recognised that, rather than a high bioburden level alone being detrimental to wound healing, it is the virulence of the invading microorganism and the host's immune status that can affect clinical outcomes. Bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, have developed a range of virulence factors to help them overcome host defences and proliferate within the underlying soft tissue. More specifically, bacterial proteases are one such virulence factor that has been implicated in promoting the invasion and destruction of the host tissue. Because of the complexities of microorganisms, the proteases can negatively impact the wound environment, leading to delayed wound healing. The aim of the present paper is to describe various extracellular bacterial proteases; review the impact they have on the wound environment, the host immune response and biofilms; and discuss potential wound management strategies against them. The evidence discussed suggests that proteases may play a profound role in wound infections, contribute to the development of an inflammatory response and impede wound healing.

Ointments containing Ceratothoa oestroides extract: Evaluation of their healing potential in the treatment of diabetic foot ulcers

“…Lower extremity wounds including DFUs are strongly associated with microbial infection . Microbial levels, virulence of the infectious agent as well as host's immune status are suggested to exert a combined detrimental effect in wound infections, contributing to the development of inflammation and impeding wound repair mechanisms . Recent data propose that inhibition of bacterial proteases is a potential new therapeutic target in chronic wound infections.…”

“…24 Microbial levels, virulence of the infectious agent as well as host's immune status are suggested to exert a combined detrimental effect in wound infections, contributing to the development of inflammation and impeding wound repair mechanisms. 25 Recent data propose that inhibition of bacterial proteases is a potential new therapeutic target in chronic wound infections. Our findings that show the significant antimicrobial activity of C. oestroides extract selectively against Gramnegative bacteria suggest that this could be an important factor for the expression of its wound healing effect in DFUs ( Table 2).…”

Exogenous Protein as an Environmental Stimulus of Biofilm Formation in Select Bacterial Strains

“…Some proteases are identified as virulence factors in pathogens including Serratia [29] and Pseudomonas aeruginosa [30] [33]. The simplistic view of these extracellular proteases is that they are foraging for nutrients and clear habitats to occupy as well as impeding host immune responses that are protein based.…”

Latest Advances on Bacterial Cellulose-Based Antibacterial Materials as Wound Dressings

“…BC, as one of the promising wound dressing materials, can control wound exudate and provide moist environment for wound healing (Nuutila and Eriksson, 2020), but it lacks antibacterial activity that limits its application. Complications can easily occur in chronic wounds where severe physiological changes or tumorigenesis may happen, which can lead to excessive production of exudates containing high levels of tissue-destructive proteases and contamination of wounds by foreign bodies (e.g., bacteria) because of inflammatory reactions (Lindsay et al, 2017;Ruf et al, 2017). For example, more than 50% of diabetic chronic ulcers are infected, and the infection is one of the most common and serious sequelae during wound FIGURE 3 | (A) General introduction of BC tissue structure (Shao et al, 2016a;Tayeb et al, 2018).…”