The biofilm lifestyle of the human skin microbiota

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INTRODUCTION
The skin accommodates hundreds of microbial species that constitute the human skin microbiota, including eukaryotes, bacteria, and viruses. After birth, distinct microbial communities colonize the skin at different body sites creating physiological and immunological niches (1). Skin microbiota significantly contributes to health and disease by sustaining the epidermal barrier function, the immune homeostasis, and limiting the growth of pathogenic bacteria (2). The resident microorganisms metabolize nutrients from the host’s skin secretions creating a complex ecological system through dynamic interactions within the microbial communities and with the host. Skin microbiota varies greatly at inter- and intrapersonal levels but is relatively temporally stable (3). Culture- and sequencing-based studies have mainly focused on characterizing the skin’s bacterial and fungal communities. Based on sequencing analysis of phylogenetic marker genes, such as the bacterial 16S ribosomal RNA (rRNA) and fungal internal transcribed spacer (ITS), major bacterial phyla belong to Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes (4, 5). Bacteria and fungi adapt to life on skin surfaces by activating several metabolic changes, including the production of the extracellular polymeric substances (EPS) that hold bacterial communities together and the regulation of quorum-sensing genes that mediate microbial communication between cells. In this state, microorganisms form networks leading to differentiation and community-like lifestyle termed biofilms. Microbial biofilms confer a protective environment to community members, which often translates into virulence, pathogenesis, or tolerance to antibiotics agents (6). Biofilm formation includes three stages: adhesion, proliferation, and detachment. Once attached to a surface, microbial cells initiate to produce the EPS that promotes aggregation and the establishment of microcolonies. The expansion of the microcolonies is in the initial phase reversible and attached to the surface.
Subsequently, microbial cells develop a mature biofilm. Mature biofilms are characterized by channels through which nutrients can penetrate deeper biofilm layers. In this phase, EPS generally occupies 5%–30% of the volume of the biofilm with a thickness ranging from a few microns to millimeters (7). In addition, the production of quorum sensing factors by the microbial cell within the biofilm promotes cell detachment and biofilm expansion (8). In particular, cell detachment is critical in biofilm-associated infection, allowing cells to spread through new sites (8). Antimicrobial treatments are usually helpful in controlling the exacerbation of infections induced by free-floating microorganisms. Still, they are frequently not effective in eradicating medical-device infections or biofilm-related chronic diseases (8). Consequently, cells forming biofilms can persist and survive even after decontamination procedures representing the source for human and animal infections (8).
The factors limiting antimicrobial efficacy are associated with different processes, such as poor biofilm penetration, metabolic inhibition, as well as the presence of quiescent cells (persisters). Thus, once a biofilm is established, it becomes difficult to eradicate with conventional antimicrobial therapies. The presence of dysbiosis and the development of pathogenic biofilms have been associated with several dermatological diseases, including chronic wounds, acne, atopic dermatitis (AD), and infections following dermal fillers (6, 9, 10). This review provides an update on the basic mechanisms and competitive dynamics modulating the homeostasis of the skin microbiota and biofilm formation in major dermatological disorders to increase awareness of more specific therapeutic approaches.