SPaCE Swab: Point-of-Care Sensor for Simple and Rapid Detection of Acute Wound Infection

Abstract

Wound infection is commonly observed after surgery and trauma but is difficult to diagnose and poorly defined in terms of objective clinical parameters. The assumption that bacteria in a wound correlate with infection is false; all wounds contain microorganisms, but not all wounds are clinically infected. This makes it difficult for clinicians to determine true wound infection, especially in wounds with pathogenic biofilms. If an infection is not properly treated, pathogenic virulence factors, such as rhamnolipids from Pseudomonas aeruginosa , can modulate the host immune response and cause tissue breakdown. Life-threatening sepsis can result if the organisms penetrate deep into host tissue. This communication describes the sensor development for five important clinical microbial pathogens commonly found in wounds: Staphylococcus aureus , P. aeruginosa , Candida albicans/auris, and Enterococcus faecalis (the SPaCE pathogens). The sensor contains liposomes encapsulating a self-quenched fluorescent dye. Toxins, expressed by SPaCE infecting pathogens in early-stage infected wounds, break down the liposomes, triggering dye release, thus changing the sensor color from yellow to green, an indication of infection. Five clinical species of bacteria and fungi, up to 20 strains each (totaling 83), were grown as early-stage biofilms in ex vivo porcine burn wounds. The biofilms were then swabbed, and the swab placed in the liposome suspension. The population density of selected pathogens in a porcine wound biofilm was quantified and correlated with colorimetric response. Over 88% of swabs switched the sensor on (10 7 –10 8 CFU/swab). A pilot clinical study demonstrated a good correlation between sensor switch-on and early-stage wound infection.

Advances in the Sensing and Treatment of Wound Biofilms

“…Not all bacterial species found in wounds cause infection [14] . Detecting wound infections can be challenging, especially in wounds with pathogenic biofilms.…”

“…[13] Not all bacterial species found in wounds cause infection. [14] Detecting wound infections can be challenging, especially in wounds with pathogenic biofilms.T herefore,a n approach to detect specific bacterial species on the wound site is vital. Different in vitro and in vivo studies have investigated biofilms on wounds.B iofilms can be divided into two main categories:c ommensal and pathogenic.P athogenic biofilms differ from commensal ones in several ways,i ncluding the presence of more upregulated genes.This promotes excessive levels of degradation enzymes (matrix metalloproteinases (MMPs)), the growth of EPS,a nd increased microbial proliferation and dissemination (which characterize chronic wounds).…”

“…Thet et al [14] describe as ensor for detecting skin pathogenic bacteria at an early stage during the formation of biofilms.Afluorescent dye is encapsulated within liposomes. Toxins from infecting bacteria cause liposomes to burst, trigger dye activation, and cause the sensor color to turn from yellow to green, demonstrating infection (Figure 3a).…”

Surface Plasmon Resonance Monitoring of Mono-Rhamnolipid Interaction with Phospholipid-Based Liposomes

“…A good correlation was demonstrated between the fluorescent sensor switch-on and early-stage wound infection. 51 A high performance liquid chromatography coupled to a charged-aerosol detection (HPLC-CAD) method was also developed by Behrens et al with a LoD for RLs of 1 µg mL −1 . 52 One can note that the LoD reached by this highly sensitive technique is close to that of the proposed MP-SPR technique in this work.…”

Composites Based on Gellan Gum, Alginate and Nisin-Enriched Lipid Nanoparticles for the Treatment of Infected Wounds

“…The presence of pathogenic bacteria at the wound site and subsequent development of bacterial infection are recognized as major factors compromising this process [ 3 ]. Bacteria can delay the healing procedure at best but can even lead to systemic infection and death at worst [ 1 , 4 ]. Opportunistic bacteria, such as Staphylococcus aureus , Streptococcus pyogenes , Escherichia coli , or Pseudomonas aeruginosa , easily colonize the wound site and create a protective biofilm, which makes the infection even more challenging to cure [ 5 , 6 , 7 ].…”