| Research into the biofilm phenotype, spanning over
almost three decades, has presented us with overwhelming evidence of its
clinical relevance. Still, no approved drugs specifically targeting bacterial
biofilms exist, and susceptibility testing against biofilms is conspicuously
missing from antibiotic discovery pipelines. AMPs with activity against
biofilms offer a promising avenue for the development of new standalone
therapeutics or adjuvants acting synergistically with pre-existing
antibiotics.
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| The dPABBs webserver is an attempt to develop a
prediction strategy for the identification and optimisation of such
anti-biofilm peptides, offering a comprehensive platform that allows the user
to check both peptides and protein fragments for potential anti-biofilm
activity and provides features like simultaneous multi-model predictions and
mutant generation.
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Schematic representation of the biofilm ultrastructure: The bacterial cells are present in matrix-enclosed "towers" or microcolonies, which behave like the structural units of a biofilm. In natural as well as human pathogenic systems, biofilms are predominantly polymicrobial (microcolonies 'A' and 'B', constructed by the green species 'A' and orange species 'B', respectively). The synergy with multiple bacterial species within a single community confers a competitive advantage to the residents of a biofilm. The microcolonies are interspersed with a network of open water channels that distribute nutrients and oxygen to different locations in the biofilm, allowing it to grow in both complexity and thickness. However, a decreasing gradient of nutrient and oxygen availability still exists between the surface and the deeper layers of the biofilm (depicted as a gradient of the colour yellow) leading to a varied population of cells in differential states of growth (depicted in shades of green and orange for the respective species). More metabolically active cells (dark green/orange) are found in the outer layers and the slow-growing, 'persister' cells (lighter green/orange) are present in the oxygen and nutrient-deprived inner layers, hence phenotypic variations arise as a result of individual cells responding to their respective microenvironments.
Bacteria use a sophisticated system of intercellular communication known as
quorum sensing (QS) that involves the production, detection and response to
signalling molecules called autoinducers (AI). There are specific autoinducing
molecules for intra-species signalling (depicted as violet diamonds in species
'A' and as red triangles in species 'B') and a "universal language" (depicted
by blue circles) for inter-species communication. |
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