Distribution of edin in Staphylococcus aureus isolated from diabetic foot ulcers

Abstract

Staphylococcus aureus is both a common colonizer of human skin and the most frequently isolated pathogen in diabetes foot infections (DFIs). The spread of DFI to soft tissue and bony structures is a major causal factor for lower-limb amputation. It is therefore of great importance to differentiate colonizing from infecting strains of S. aureus. Epidermal cell differentiation inhibitors known as EDIN and EDIN-like factors, a group of toxins targeting RhoA master regulator of the actin cytoskeleton, may confer virulence properties on S. aureus. In this study, for the first time, analysis of S. aureus strains, recovered in DFIs at an initial stage and during the follow-up, showed that 71.4% of edin-positive strains were associated with moderate-to-severe infections (grades 3 and 4 of the IDSA/IWGDF classification) compared with 28.6% of edin-positive strains associated with low-grade infections. Most of these strains were edin-B positive (86.7%) and belonged to CC25/28-MSSA (n = 10). One edin-B-positive ST152-MSSA strain was negative for the two highly prevalent predictive markers of infecting strains (lukDE and hlgv). Collectively, this points towards the edin-B encoding gene as a bonafide subsidiary predictive risk marker of DFI.

ADP-ribosylating toxins modifying the actin cytoskeleton

“…In contrast, EDIN produced by certain S. aureus strains is considered an important virulence factor involved in impetigo, diabetic foot ulcers, and other skin infections [25,[47][48][49]. S. aureus can invade eukaryotic cells and release EDIN intracellularly, which contributes to actin cytoskeleton disorganization and tissue destruction [50].…”

Set Phages to Stun: Reducing the Virulence of Staphylococcus aureus in Diabetic Foot Ulcers

“…In this issue of Diabetes, we read with interest the study by Messad et al (8), which tantalizingly suggests it may be possible to differentiate a "colonizing" from a more microbiologically nefarious phenotype of S. aureus, the "prince of pedal pathogens." Even more promising is that this work may identify an approach to "stun" a pathogenic colony into one that seeks peaceful coexistence (8).…”

“…By this mechanism, S. aureus, with its great potential for pathogenicity, may masquerade as a harmless bacterium when colonizing a chronic wound. Messad et al (8) demonstrate that one mechanism for turning a pathogen into a pal is to promote biofilm formation. Another may be that bacterial cells with an integrated prophage are immune to superinfection and have a considerably smaller chance (10 25 ) of being lysed by the infecting prophage (9).…”

“…Specifically, marine phages have been shown to modulate bacterial host metabolism and energy production by harboring genes that are specifically adapted to their environmental niche (e.g., surface vs. deep ocean) (17). Given the new data presented by Messad et al (8), the ROSAlike prophage may provide a similar beneficial role to its bacterial host by increasing biofilm formation and promoting colonization within the DFU. In light of the continuing problem of defining infection in a chronic wound, gaining a better understanding of the virome may open a new approach to selecting treatments and improving outcomes (Fig.…”

“…The fascinating findings of Messad et al (8) suggest that we might be able to practically (and rapidly) detect phages present within chronic wounds to identify ones that might either increase or decrease the degree of bacterial virulence. If so, perhaps we can use this new information to help decide which patients need antimicrobial therapy and which do not-a major issue in this era of rising antibiotic resistance.…”