Biofilms in Dermatology
Biofilms are diverse communities of microorganisms embedded within a self-produced matrix of extracellular polymeric substance which are firmly attached to biotic or abiotic surfaces. Approximately 80% of all human infections are associated with biofilms and evidence for their role in an ever-growing number of cutaneous disorders is constantly unfolding. Biofilms present a difficult challenge to clinicians due to their persistent nature, inability to be cultured with standard techniques, and resistance to conventional antimicrobial therapy. Although limited treatment options are presently available, better understanding of the molecular biology of biofilms and their pathogenicity will likely lead to the development of novel anti-biofilm agents for clinical use.
While bacteria have classically been viewed from the perspective of planktonic, free floating pathogens proliferating and exerting their virulence as individual organisms, it is now recognized that microbes also can exist as multicellular consortiums known as biofilms. (Figure 1) Several advantages exist for bacteria that live in a biofilm phenotype including structural stability, firm adherence to biotic or abiotic surfaces, increased virulence, and resistance to both antimicrobial therapy and the host immune response. Organisms within biofilms are embedded in a glycocalyx, a self-produced matrix of extracellular polymeric substance (EPS) composed of polysaccharides, proteins, lipids, and extracellular DNA (eDNA). The EPS is considered to be the hallmark of biofilm formation and in addition to facilitating attachment, it also serves a protective function by preventing neutrophilic penetration, masking phagocytic detection of opsonins, and sequestering host antibodies, as well as complement factors. The formation and behavior of the entire biofilm community is directed by signaling molecules that are produced when microorganisms reach a critical number. This phenomenon is termed quorum sensing (QS) and has also been shown to regulate the expression of virulence factors as well as modulate host immunity.
(Enlarge Image)
Figure 1.
Scanning electron micrograph demonstrating the presence of mixed species biofilm in a chronic wound. Both cocci and bacilli are seen embedded in an amorphous matrix characteristic of biofilm formation.Figure from James GA, Swogger E, Wolcott R, et al. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):page 42, Figure 1D. Reprinted with permission from John Wiley and Sons.
Biofilms have been associated with approximately 80% of all human infections, yet their detection is extremely difficult with the use of routine culture techniques. New methods to detect biofilm-associated organisms are under development. For example, denaturating gradient gel electrophoresis and 16S rRNA sequencing are currently being used successfully in the research setting and may someday be available for use in clinical practice. Currently, biofilms cannot be visualized in skin biopsies submitted for routine light microscopy due to collapse of the glycocalyx during the dehydration process9 and require special techniques for visualization of the intact biofilm structure such as electron, epifluorescence, or confocal laser scanning microscopy (CLSM). Conventional therapy is characteristically ineffective against biofilms, as the minimum inhibitory concentration (MIC) of antimicrobial agents has been shown to be 10 to 1000 fold greater than for planktonic organisms. Antimicrobial resistance can be attributed to the EPS serving as a physical barrier to antibiotic penetration, plasmid exchange facilitated by close proximity between organisms, and the low metabolic activity and growth rate observed within biofilms. In addition, decreased susceptibility to antimicrobial agents may also be related to an increased frequency of mutations, which result in upregulation of efflux pumps and antibiotic degrading enzymes such as betalactamase.
Biofilms present a unique challenge to today's clinician and evidence for their involvement throughout dermatology is constantly unfolding. Herein, we will present current knowledge regarding the role of biofilms in cutaneous disease along with potential therapeutic strategies for the management of biofilmassociated infections.
Abstract and Introduction
Abstract
Biofilms are diverse communities of microorganisms embedded within a self-produced matrix of extracellular polymeric substance which are firmly attached to biotic or abiotic surfaces. Approximately 80% of all human infections are associated with biofilms and evidence for their role in an ever-growing number of cutaneous disorders is constantly unfolding. Biofilms present a difficult challenge to clinicians due to their persistent nature, inability to be cultured with standard techniques, and resistance to conventional antimicrobial therapy. Although limited treatment options are presently available, better understanding of the molecular biology of biofilms and their pathogenicity will likely lead to the development of novel anti-biofilm agents for clinical use.
Introduction
While bacteria have classically been viewed from the perspective of planktonic, free floating pathogens proliferating and exerting their virulence as individual organisms, it is now recognized that microbes also can exist as multicellular consortiums known as biofilms. (Figure 1) Several advantages exist for bacteria that live in a biofilm phenotype including structural stability, firm adherence to biotic or abiotic surfaces, increased virulence, and resistance to both antimicrobial therapy and the host immune response. Organisms within biofilms are embedded in a glycocalyx, a self-produced matrix of extracellular polymeric substance (EPS) composed of polysaccharides, proteins, lipids, and extracellular DNA (eDNA). The EPS is considered to be the hallmark of biofilm formation and in addition to facilitating attachment, it also serves a protective function by preventing neutrophilic penetration, masking phagocytic detection of opsonins, and sequestering host antibodies, as well as complement factors. The formation and behavior of the entire biofilm community is directed by signaling molecules that are produced when microorganisms reach a critical number. This phenomenon is termed quorum sensing (QS) and has also been shown to regulate the expression of virulence factors as well as modulate host immunity.
(Enlarge Image)
Figure 1.
Scanning electron micrograph demonstrating the presence of mixed species biofilm in a chronic wound. Both cocci and bacilli are seen embedded in an amorphous matrix characteristic of biofilm formation.Figure from James GA, Swogger E, Wolcott R, et al. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):page 42, Figure 1D. Reprinted with permission from John Wiley and Sons.
Biofilms have been associated with approximately 80% of all human infections, yet their detection is extremely difficult with the use of routine culture techniques. New methods to detect biofilm-associated organisms are under development. For example, denaturating gradient gel electrophoresis and 16S rRNA sequencing are currently being used successfully in the research setting and may someday be available for use in clinical practice. Currently, biofilms cannot be visualized in skin biopsies submitted for routine light microscopy due to collapse of the glycocalyx during the dehydration process9 and require special techniques for visualization of the intact biofilm structure such as electron, epifluorescence, or confocal laser scanning microscopy (CLSM). Conventional therapy is characteristically ineffective against biofilms, as the minimum inhibitory concentration (MIC) of antimicrobial agents has been shown to be 10 to 1000 fold greater than for planktonic organisms. Antimicrobial resistance can be attributed to the EPS serving as a physical barrier to antibiotic penetration, plasmid exchange facilitated by close proximity between organisms, and the low metabolic activity and growth rate observed within biofilms. In addition, decreased susceptibility to antimicrobial agents may also be related to an increased frequency of mutations, which result in upregulation of efflux pumps and antibiotic degrading enzymes such as betalactamase.
Biofilms present a unique challenge to today's clinician and evidence for their involvement throughout dermatology is constantly unfolding. Herein, we will present current knowledge regarding the role of biofilms in cutaneous disease along with potential therapeutic strategies for the management of biofilmassociated infections.