P. Gilbert

Cationic antimicrobials have been in general use within clinical and domestic settings for over half a century. Recently, the use of antiseptics and disinfectants has been questioned in such settings because of the possibility that chronic exposure of the environment to such agents might select for less susceptible strains towards these agents and towards third party antibiotics. Whilst no supportive evidence has emerged from retrospective field studies of high use environments such debate has tempered new applications for these molecules. In the clinic, use of antiseptics, together with products, such as dressings, catheters and sutures, which are impregnated with biocides has increased. Prominent amongst these biocides are the cationics. Much of the research pertaining to the mechanisms of action of cationic antibacterials was conducted in the 1960s and 1970s and has not been subject to extensive review. Analysis of available publications suggest that monoquaternary ammonium compounds (QAC, cetrimide, benzalkonium chloride), biquaternaries and bisbiguanides (Chlorhexidine, Barquat), and polymeric biguanides (Vantocil, Cosmocil) whilst having similarities in action mechanism, differ substantially in the nature of their interaction with cell envelopes. This has profound implications in terms of cross-resistance where changes in susceptibility towards QAC is not reflected in changes towards other cationics. This review examines action mechanisms for these agents and highlights key differences that render them distinct categories of antibacterial agent. © 2005 The Society for Applied Microbiology.

The processes associated with early events in biofilm formation have become a major research focus over the past several years. Events associated with dispersion of cells from late stage biofilms have, however, received little attention. We demonstrate here that dispersal of Pseudomonas aeruginosa PAO1 from biofilms is inducible by a sudden increase in carbon substrate availability. Most efficient at inducing dispersal were sudden increases in availability of succinate > glutamate > glucose that led to approximately 80% reductions in surface-associated biofilm biomass. Nutrient-induced biofilm dispersion was associated with increased expression of flagella (fliC) and correspondingly decreased expression of pilus (pilA) genes in dispersed cells. Changes in gene expression associated with dispersion of P. aeruginosa biofilms were studied by using DNA microarray technology. Results corroborated proteomic data that showed gene expression to be markedly different between biofilms and newly dispersed cells. Gene families that were upregulated in dispersed cells included those for flagellar and ribosomal proteins, kinases, and phage PF1. Within the biofilm, genes encoding a number of denitrification pathways and pilus biosynthesis were also upregulated. Interestingly, nutrient-induced dispersion was associated with an increase in the number of Ser/Thr-phosphorylated proteins within the newly dispersed cells, and inhibition of dephosphorylation reduced the extent of nutrient-induced dispersion. This study is the first to demonstrate that dispersal of P. aeruginosa from biofilms can be induced by the addition of simple carbon sources. This study is also the first to demonstrate that dispersal of P. aeruginosa correlates with a specific dispersal phenotype.

Microbial biofilms, where organisms are intimately associated with each other and a solid substratum through binding and inclusion within an exopolymer matrix, are widely distributed in nature and disease. In the mouth, multispecies biofilms are associated not only with dental plaque and tooth decay but also with soft tissues of the buccal cavity and with most forms of periodontal disease. Organization of micro-organisms within biofilms confers, on the component species, properties which are not evident with the individual species grown independently or as planktonic populations in liquid media. While many of these properties relate to the establishment of functional, mixed-species consortia within the exopolymeric matrices, others relate to the establishment of physico-chemical gradients, within the biofilm, that modify the metabolism of the component cells. A consequence of biofilm growth that has profound implications for their control in the environment and in medicine is a markedly enhanced resistance to chemical antimicrobial agents and antibiotics. Mechanisms associated with such resistance in biofilms will form the substance of the present review. While some aspects of biofilm resistance are yet only poorly understood, the dominant mechanisms are thought to be related to: (i) modified nutrient environments and suppression of growth rate within the biofilm; (ii) direct interactions between the exopolymer matrices, and their constituents, and antimicrobials, affecting diffusion and availability; and (iii) the development of biofilm/attachment-specific phenotypes.

Article de synthese portant sur les facteurs influancant la sensibilite resistance des microorganismes aux antimicrobiens.