Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review

Abstract

Chronic wounds, defined by their resistance to care after four weeks, are a major concern, affecting millions of patients every year. They can be divided into three types of lesions: diabetic foot ulcers (DFU), pressure ulcers (PU), and venous/arterial ulcers. Once established, the classical treatment for chronic wounds includes tissue debridement at regular intervals to decrease biofilm mass constituted by microorganisms physiologically colonizing the wound. This particular niche hosts a dynamic bacterial population constituting the bed of interaction between the various microorganisms. The temporal reshuffle of biofilm relies on an organized architecture. Microbial community turnover is mainly associated with debridement (allowing transitioning from one major representant to another), but also with microbial competition and/or collaboration within wounds. This complex network of species and interactions has the potential, through diversity in antagonist and/or synergistic crosstalk, to accelerate, delay, or worsen wound healing. Understanding these interactions between microorganisms encountered in this clinical situation is essential to improve the management of chronic wounds.

Keywords: biofilm; chronic wounds; colonization; cutaneous microbiota; microbial crosstalk; microbial interactions; virulence.

Figure 1

Biofilm organization at the wound level. Commensal and pathogenic bacteria colonized the wound through coaggregation/repelling either from the adjacent skin or through hand carriage. Arrows represent positive interactions, while the flathead arrow represents negative interactions. Time evolution is represented with a shaded red arrow. Bacteria are represented encased in biofilm matrix (green), which will remodel itself relying on bacterial interactions to further cover the wound. Biofilm is in contact with intact or necrotic cells of the different epidermal layers. Gram-negative, strict aerobes are represented in green and can “cap” the ulcer, and Gram-positive anaerobe/aerotolerant cocci are in yellow. Functionally equivalent pathogroups (FEPs) are illustrated at the core of Corynebacterium (dark blue bacilli) microniche as an anaerobic cluster of Gram-positive (brown, light brown, and blue). The dioxygen gradient is represented as a gradient blue triangle.

Figure 2

Selected network of interactions described or expected in a chronic wound environment illustrating the diversity involved within this particular niche. Fungi, Gram-negative, and Gram-positive microorganisms are highlighted in yellow, green, and blue, respectively. S. aureus is represented at the center of this network of interaction in yellow. Grey Gram-positive cocci represent Staphylococci (S. aureus and Coagulase negative Staphylococci (CoNS)). They interact through Agr system by benefiting from S. aureus autoinducers production and/or production of their own autoinducers antagonizing S. aureus Agr loop. Green/yellow helix represents siderophore used for extracellular iron acquisition. It is represented as complexed with Fe²⁺ (red core). Solid lines illustrate direct interaction between microorganisms, whereas dashed lines illustrate indirect interaction. Shaded arrows indicate dynamic interaction. Arrows highlight positive interaction, and flathead arrows highlight negative microbial interactions. ATB-R, antibiotic resistance; HQNO, hydroxyquinoline N-oxide (mediator of P. aeruginosa quorum sensing); NET, neutrophils extracellular trap (neutrophils are activated to enter this pathway through S. aureus virulence factors; after releasing bacterial DNA and histone in the extracellular environment, SufA and FnBP can degrade histones and thus inhibit their bactericidal activity).