Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.

/pdf/bacterial-biofilms-a-common-cause-of-persistent-infections-2rbq14h2a8.pdf

Bacterial biofilms : A common cause of persistent infections

Bacteria in nature often exist as sessile communities called biofilms. These communities develop structures that are morphologically and physiologically differentiated from free-living bacteria. A cell-to-cell signal is involved in the development of Pseudomonas aeruginosa biofilms. A specific signaling mutant, a lasI mutant, forms flat, undifferentiated biofilms that unlike wild-type biofilms are sensitive to the biocide sodium dodecyl sulfate. Mutant biofilms appeared normal when grown in the presence of a synthetic signal molecule. The involvement of an intercellular signal molecule in the development of P. aeruginosa biofilms suggests possible targets to control biofilm growth on catheters, in cystic fibrosis, and in other environments where P. aeruginosa biofilms are a persistent problem.

https://science.sciencemag.org/content/sci/280/5361/295.full.pdf

The involvement of cell-to-cell signals in the development of a bacterial biofilm

According to a public announcement by the US National Institutes of Health
 , “Biofilms are medically important, accounting for over 80% of microbial infections in the body”. Yet bacterial biofilms remain poorly understood and strategies for their control remain underdeveloped. Standard antimicrobial treatments typically fail to eradicate biofilms, which can result in chronic infection and the need for surgical removal of afflicted areas. The need to create effective therapies to counter biofilm infections presents one of the most pressing challenges in anti-bacterial drug development. In this article, the mechanisms that underlie biofilm resistance to antimicrobial chemotherapy will be examined, with particular attention being given to potential avenues for the effective treatment of biofilms.

/pdf/understanding-biofilm-resistance-to-antibacterial-agents-pnlgfboaq5.pdf

Understanding biofilm resistance to antibacterial agents.

Dental biofilms: difficult therapeutic targets.

http://ssu.ac.ir/cms/fileadmin/user_upload/Mtahghighat/tfood/ARTICLES/microb-safety/Significance_of_microbial_biofilms_in_food_industry_a_review.pdf

Significance of microbial biofilms in food industry: a review

The bioelectric effect, in which electric fields are used to enhance the efficacy of biocides and antibiotics in killing biofilm bacteria, has been shown to reduce the very high concentrations of these antibacterial agents needed to kill biofilm bacteria to levels very close to those needed to kill planktonic (floating) bacteria of the same species. In this report, we show that biofilm bacteria are readily killed by an antibiotic on all areas of the active electrodes and on the surfaces of conductive elements that lie within the electric field but do not themselves function as electrodes. Considerations of electrode geometry indicate that very low (< 100 microA/cm2) current densities may be effective in this electrical enhancement of antibiotic efficacy against biofilm bacteria, and flow experiments indicate that this bioelectric effect does not appear to depend entirely on the possible local electrochemical generation of antibacterial molecules or ions. These data are expected to facilitate the use of the bioelectric effect in the prevention and treatment of device-related bacterial infections that are caused by bacteria that grow in biofilms and thereby frustrate antibiotic chemotherapy.

Mechanism of electrical enhancement of efficacy of antibiotics in killing biofilm bacteria.

Bacteria that grow in association with medical devices always form slime enclosed biofilms, within which they are protected, to a large extent, from the bactericidal activity of chemical biocides and antibiotics. Mature biofilms (> 7 days) are demonstrably resistant to 500-5,000 times the concentrations of these agents than are necessary to kill free floating (planktonic) cells of the same organism. The authors have discovered that this well established inherent resistance of biofilm bacteria to antibacterial agents can be completely obviated if these agents are applied to these adherent populations within an electric field. The killing of biofilm bacteria by antibiotics can be dramatically enhanced by relatively weak electric fields (1.5 V/cm and 15 microA/cm2) that, in themselves, have no deleterious effects on these slime protected populations adherent to plastic or metal surfaces. This bioelectric technology can readily be used to enhance the preimplantation sterilization of medical devices by biocides. The authors suggest that it may also be used to control biofilm formation and consequent infection by electrically enhanced perioperative antibiotic prophylaxis and by electrically enhanced penetration of antibiotics to kill the biofilm bacteria that form the inherently resistant nidus of chronic device related infections.

Prevention and control of bacterial infections associated with medical devices.

Thebioelectric elfect, inwhichelectric fields areusedtoenhance theefficacy ofbiocides andantibiotics in killing biofilm bacteria, hasbeenshowntoreduce theveryhighconcentrations ofthese antibacterial agents needed tokill biofilm bacteria tolevels veryclose tothose needed tokill planktonic (floating) bacteria ofthe same species. Inthis report, we showthatbiofilm bacteria arereadily killed byan antibiotic on all areasofthe active electrodes andon thesurfaces ofconductive elements thatliewithin theelectric field butdonot themselves function aselectrodes. Considerations ofelectrode geometry indicate that verylow(<100FLA/cm2) current densities may beeffective inthis electrical enhancement ofantibiotic efficacy against biofilm bacteria, andflowexperiments indicate thatthis bioelectric eflect doesnotappear todependentirely on thepossible local electrochemical generation ofantibacterial molecules orions. Thesedata areexpected tofacilitate theuse ofthebioelectric effect intheprevention andtreatment ofdevice-related bacterial infections that arecaused bybacteria that grow inbiofilms andthereby frustrate antibiotic chemotherapy. Workinmany laboratories (16, 17,32), including our own (3,12,33),hasclearly established thatbiofilm bacteria are resistant toantibiotics andbiocides atlevels 500to5,000 times higher thanthose needed tokill planktonic cells ofthesame species. Themechanism ofthis inherent resistance ofglycocalyx-enclosed biofilm bacteria toantimicrobial agentsisnot conclusively established butappearstodepend on bothdiffusionlimitation (25)andphysiological properties associated withlowgrowth rates(8,9,16,17)inbiofilm populations. Direct examination ofthesurfaces ofmedical devices that have becomethefoci ofdevice-related bacterial infections shows that these pathogens growinwell-developed adherent biofilms (12), andclinical experience (21)indicates thatthese chronic infections arehighly refractory toantibiotic therapy. Consequently, device-related bacterial infections are aggressively treated withcombinations ofantibiotics (2,27), butinmany cases,thebiofilm-colonized

Kan Lam

Papers

Mechanism of electrical enhancement of efficacy of antibiotics in killing biofilm bacteria.

Prevention and control of bacterial infections associated with medical devices.

Mechanism ofElectrical Enhancement ofEfficacy ofAntibiotics inKilling Biofilm Bacteria