The response of Pseudomonas aeruginosa biofilm to the presence of a glass polyalkenoate cement formulated from a silver containing glass

Excerpt

Biofilms are microbial derived sessile communities characterized by cells that are irreversibly attached to a substratum, or to each other, and embedded in a matrix of extracellular polymeric substances that they have produced [1]. Such microorganisms exhibit an altered phenotype with respect to growth rate and gene transcription [2]. Biofilms forming on implanted medical devices are problematic as the extra cellular matrix exported by the microorganisms along with the changes in their physiology result in the requirement to remove the device to effect a cure [3, 4]. Pseudomonas aeruginosa is a human opportunistic pathogen that colonizes biotic and abiotic surfaces and has emerged as a primary source of nosocomial infections [5], especially in cystic fibrosis sufferers and immuno-compromised patients [6]. The bacterium almost never infects uncompromised tissues, yet there is hardly any tissue that it cannot infect if the tissue defences are compromised in some manner, such as in severe burns sufferers [7]. In the United States, P. aeruginosa ranked first among all nosocomial pathogens related to pneumonia in intensive care units reported to the National Nosocomial Infection Surveillance System [8]. Pseudomonas sp. in general and P. aeruginosa, specifically, has resistance to antibiotics including aminoglycosides and quinolones, and this is steadily increasing [9]. The mechanisms of biofilm formation are poorly understood and effective prevention and therapeutic strategies still need to be developed for device-associated infections. Treatment with antibiotics can slow down biofilm progression by eliminating planktonic cells and interfering with biofilm metabolism [10], but complete removal is rare. Other eradication methods that have been employed include prevention of initial attachment of bacterial cells by constructing materials into which antimicrobial agents have been incorporated [10] and minimizing biofilm formation by the disruption of quorum-signalling molecules, allowing for improved inactivation and removal [11]. Glass polyalkenoate cements (GPCs), formed by the reaction between an ion-leachable glass and an aqueous solution of polyacrylic acid (PAA) [12], are both antibacterial and cariostatic [13]; properties related to their ability to release beneficial amounts of therapeutic ions [14, 15]. Studies have shown that inhibition of bacterial growth correlates with zinc (Zn²⁺) and silver (Ag⁺) ion release from novel GPCs [16, 17]. Zn²⁺ has been shown to inhibit multiple activities in the bacterial cell including glycolysis, transmembrane protein translocation and acid tolerance [18]. It also influences pH, which rises throughout glycolysis via the action of Zn²⁺ on the bacterial cell wall and therefore leaves an excess of OH⁻ that results in a favourable bioactive response [19]. The minimum Zn²⁺ concentration required for P. aeruginosa inhibition is 6.02 × 10⁻⁴ μg/mL [20] and 8 μg/mL for biofilm inhibition [21]. Ag⁺ is also a known antibacterial agent [22, 23]. To have antimicrobial efficacy against P. aeruginosa bacteria, Ag⁺ must be released in biocidal concentrations of 1.102 × 10⁻⁶ μg/mL [24] and 5 μg/mL for biofilm inhibition [25]. Ag⁺ avidly binds to negatively charged components in proteins and nucleic acids, thereby causing structural changes in bacterial cell walls, membranes and nucleic acids that affect viability [26]. …