Bacterial Surface Sensing - to Stick or not to Stick?. (360G-Wellcome-103882_Z_14_Z)

How can we control bacterial attachment to manmade surfaces? To prevent medical-device related infections in the post-antibiotic era, we propose to answer these two specific but interlinked questions: i) How do bacteria respond dynamically to polymer surfaces? ii) What intra- and inter- cellular signalling mechanisms do bacteria employ to sense and respond to polymer surfaces? Bacteria prefer to adopt surface-associated rather than suspended, planktonic lifestyles since they offer s urvival advantages including improved access to nutrients and protection from predation[1]. Surface growth has important implications for bioenergy, biofouling and infection. Bacteria will attach to almost any surface and in the context of healthcare, medical-device centred infections pose an enormous healthcare threat particularly in this era of multi-antibiotic resistant super-bugs. Following an initial reversible attachment phase, bacterial cells become irreversibly surface-attached leading t o biofilm development which is difficult to prevent or treat. Consequently we urgently need to better understand bacteria-material surface interactions to facilitate discovery of novel anti-adherence materials. With Wellcome Trust translational funding, we successfully pioneered a high-throughput materials discovery strategy using polymer microarrays[2,3]. By correlating multi-species bacterial attachment with surface chemistry navigated using multivariate analysis of surface mass spectral in formation in over 20,000 assays using over 1300 unique copolymers, we discovered a new class of synthetic acrylate polymers which resist attachment both in vitro and in vivo2(Fig.1). These bacteria resistant polymer (BRP) chemistries could not have been predicted from our current understanding of bacterial responses to materials. The mechanism by which these BRPs resist attachment is however not understood. Bacterial attachment processes cannot be explained in simple physicochemical terms o r without considering the dynamic adaptive behaviour of bacterial cells[4,5]. While there is a significant knowledge of bacterial surface macromolecules and their role in attachment, the tactile and sensory mechanisms bacteria employ to sense that they are on or near a specific surface and to decide whether or not to stick remain poorly understood[1]. Here we offer an interdisciplinary approach, combining materials science (controllable surfaces) and molecular microbiology, in conjunction with h igh resolution state-of-the-art imaging exploiting the extensive material chemistry and attachment phenotypes obtained previously[2,3] to address the following overarching question and sub-questions below. These fundamental questions are completely outside our Wellcome Trust Translational Award which was directed towards the discovery and development of new BRP chemistries.