Novel approaches to the treatment of bacterial biofilm infections

Abstract

Bacterial infection remains a major challenge to healthcare and is responsible for significant morbidity and mortality. This situation is becoming complicated by an increasingly ageing and susceptible population and large numbers of bacterial isolates, which have developed resistance to antibiotics. Bacteria that form biofilms and colonize or infect medical devices or wounds are particularly hard to treat as biofilms are inherently highly antibiotic resistant. Most infections have a component where bacteria exist as a biofilm and as a result, prevention or treatment of biofilm-associated infections is highly important. A number of novel strategies to kill biofilms have been in development; these include the use of weak organic acids, photo irradiation and the application of bacteriophage. All have promise and are able to effectively kill biofilms in model systems, but for each there are still unanswered questions. This review summarizes the main features of biofilm infections, each of these novel approaches and the evidence that is still lacking before these potential treatments can be incorporated into clinical usage.

Linked articles: This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.

Figure 1

Biofilm contamination of catheters and wounds can lead to bacteraemia. Panels A–D show the stages of colonization of a catheter where planktonic cells attach, form micro colonies then a mature biofilm. Panels E–H depict a normal skin barrier colonized with bacteria from the flora before an injury allowing bacteria to enter lower layers, cause damage to deeper tissues and eventually enter the bloodstream.

Figure 2

Possible mechanisms of action of WOA. Panel A shows the ability of acetic acid to pass into a cell compared with hydrochloric acid and the subsequent ion trapping when it dissociates inside the cell. Panel B shows the loss of the proton motive force, which results from increasing acidity of the cytoplasm (the right side of the cell). Panel C shows the impact of the dissociated anion, here acetate, which can enter the tricarboxylic acid (TCA) cycle and cause abnormal flux of metabolites. Panel D shows the possible impact from osmotic shock on the cell.