Biofilms are surface attached microbial communities that can be found at almost any solid-liquid interface in industrial, environmental and clinical settings. There is compelling evidence that the biofilm lifestyle is an efficient means for microorganisms to define and maintain a protected niche. Biofilm associated infections cause significant morbidity and mortality. For example, the opportunistic bacterial pathogen Pseudomonas aeruginosa is responsible for persistent infections associated with cystic fibrosis (CF) lung disease, burn wounds, otorrhea, and the cornea. One of the major factors contributing to the recalcitrant nature of these infections is the ability of P. aeruginosa to form biofilms in these tissues.
Biofilm associated infections can also be caused by, e.g., several species of Streptococcus, Staphylococcus aureus, Haemophilus influenzae, Burkholderia cepacia, E. coli, and several species of Candida. Other specific infections diseases associated with biofilms include, e.g., native valve endocarditis, otitis media, chronic bacterial prostatitis, and periodontitis.
Bacteria growing in biofilms can become up to 1000-fold more resistant to antibiotics and other biocides as compared to their non-biofilm associated (or “planktonic”) counterparts. As a result of this increased resistance, biofilm infections cannot be effectively treated with conventional antibiotic therapy. There is not a single mechanism that can be ascribed to the tenacious biofilm phenotype, which is believed to arise from a multiplicity of factors, including poor antimicrobial penetration, oxygen and nutrient limitation, slow growth, and adaptive stress responses.
Similarly, a number of medical devices have been shown to be susceptible to colonization by bacteria in biofilms. For certain devices, such as urinary catheters and contact lenses, research has also elucidated the susceptibility of various materials to bacterial adhesion and biofilm formation. Urinary catheter biofilms are unique in that certain of the component organisms may alter the local pH through the production of urease, which hydrolyzes the urea of the urine to form free ammonia which, in turn, will raise the local pH and allow precipitation of minerals such as calcium phosphate (hydroxyapatite) and magnesium ammonium phosphate (struvite). These minerals will then deposit in the catheter biofilms, forming a mineral encrustation. The primary urease-producing organisms in urinary catheters are P. mirabilis, M. morganii, P. aeruginosa, K. pneumoniae, and Proteus vulgaris. Organisms that have been shown to adhere to contact lenses include P. aeruginosa, S. aureus, S. epidermidis, Serratia spp., E. coli, Proteus spp., and Candida spp. In addition, biofilms on specific devices, such as, e.g., prosthetic heart valves, central venous catheters, urinary (Foley) catheters, contact lenses, intrauterine devices, and dental unit water lines present significant clinical challenges.
Thus, the findings clearly indicate the need for new antimicrobial agents and biocides and methods of their use that are effective against biofilms. The present invention provides such methods. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.
USPTO Backgrounds
USPTO Backgrounds