Bacterial Biofilm and its Role in the Pathogenesis of Disease

Abstract

Recognition of the fact that bacterial biofilm may play a role in the pathogenesis of disease has led to an increased focus on identifying diseases that may be biofilm-related. Biofilm infections are typically chronic in nature, as biofilm-residing bacteria can be resilient to both the immune system, antibiotics, and other treatments. This is a comprehensive review describing biofilm diseases in the auditory, the cardiovascular, the digestive, the integumentary, the reproductive, the respiratory, and the urinary system. In most cases reviewed, the biofilms were identified through various imaging technics, in addition to other study approaches. The current knowledge on how biofilm may contribute to the pathogenesis of disease indicates a number of different mechanisms. This spans from biofilm being a mere reservoir of pathogenic bacteria, to playing a more active role, e.g., by contributing to inflammation. Observations also indicate that biofilm does not exclusively occur extracellularly, but may also be formed inside living cells. Furthermore, the presence of biofilm may contribute to development of cancer. In conclusion, this review shows that biofilm is part of many, probably most chronic infections. This is important knowledge for development of effective treatment strategies for such infections.

Keywords: biofilm; cancer; endocarditis; inflammatory bowel disease (IBD); otitis media; prostatitis; rhinosinusitis; urinary tract infections; vaginosis; wound infections.

Figure 1

Gallbladder stones from an asymptomatic typhoid carrier in Mexico City support biofilm formation. SEM micrographs show S. Typhi embedded in biofilms on the surfaces of gallstones at magnifications of 1500× (A), 2000× (B), 2400× (C), and 16,000× (D). R.W. Crawford et al. [73].

Figure 2

Fluorescence in situ hybridization (FISH) analysis of endometrial samples with probes targeting bacterial vaginosis-associated and other bacteria. (A) Gardnerella dominated polymicrobial biofilm attached to the endometrium. (B) Endometrial sample free of bacteria. (C) Bacteria other than Gardnerella colonizing the endometrial epithelium. Swidsinski et al. [130].

Figure 3

(a) Biofilm positive samples taken from the lateral side of concha media visualized by confocal scanning laser microscopy (Leica TCS SP2 AOBS) and (b) live/dead-staining (Invitrogen’s LIVE/DEAD BacLight™, Invitrogen, Burlington, Canada). Epithelial cells are red, and the bacteria are green. Biofilms were scored when clusters of bacteria with intact membranes were present in both the x-y and x-z axes. Courtesy of Dr. Kjell Arild Danielsen.

Figure 4

P. aeruginosa from sputum of a cystic fibrosis patient. Mucoid (large) and nonmucoid (small) colonies. The mucoid variant over-produces alginate, which is the matrix in the P. aeruginosa biofilm in the respiratory tract of cystic fibrosis patients. Mucoid colonies are only found in patients with chronic biofilm infection and alginate from mucoid colonies is therefore a biofilm-specific antigen. Høiby et al. [197].

Figure 5

Electron microscopy findings in urines from women with cystitis. TEM analysis of human cystitis urine specimens (A) revealed large collections of bacteria associated with nuclei and other cellular debris. These collections of bacteria from human urines (B) have similar morphology and organization as those recovered from intact murine intracellular bacterial communities (C). Bacteria and filaments were also observed intracellularly within exfoliated epithelial cells in a urine sample quickly fixed and analyzed from an E. coli cystitis patient (D). SEM analysis of cystitis urines deemed positive for IBCs and filaments captured large bacterial biofilm-like collections (E,F) composed of bacteria with a smaller, more coccoid morphology than typical E. coli. Long filaments were also captured by SEM (G). Scale bars, 2 μm (A,D), 1 μm (B,C), and 5 μm (E–G). Rosen et al. [222].

Figure 6

Diseases associated with bacterial biofilms.