Physiological differentiation in swarming salmonella
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AbstractSwarming behaviour in bacteria has been traditionally described as a surface motility phenotype observed on laboratory media. Swarming motility is a collective behaviour of groups of bacterial cells, and unlike the classic swimming motility in broth, vegetative cells must first differentiate into elongated and hyperflagellated swarmer cells. The extent of the morphological changes associated with swarmer differentiation can vary significantly between different organisms. Recent studies indicate that swarmer differentiation represents much more than a motility phenotype, as several clinically important attributes are co-regulated with swarming. In this work, I demonstrate that swarmer differentiation in Salmonella enterica serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antibiotics. One mechanism of resistance was directly attributed to the up-regulation of the pmrHFIJKLM operon, and evidence was presented that other mechanisms are likely associated. Adaptive antibiotic resistance in the absence of overt selection suggests that swarmer differentiation may reflect the organism's adaptation to the host environment; not due to antibiotic use, but to the role of host-derived cationic peptides and resident microflora-derived colicins and toxic metabolites that shape the intestinal ecosystem. Proteomic analyses revealed that migrating swarmer cells are metabolically differentiated compared to the vegetative swimmer cells grown in the same nutrient environment. Furthermore, once the cells have differentiated, the swarmers remain in this physiological state under conditions that do not promote the initial differentiation. The permeability of the swarmers' outer membrane was predicted to be relatively reduced, which in part accounts for the multiple antibiotic resistance phenotype. Moreover, the bacterium's capacity to override some of the classic paradigms of metabolic regulation, established in aqueous environments, represents a unique physiological response by the pathogen that may be advantageous in polymicrobial environments such as the host. In addition, cellcell signalling systems were differentially regulated, suggesting that the differentiated cells are also primed to respond to the presence of other organisms and its own increasing population. An experimental model system was developed to measure spatiotemporal gene expression patterns to study gene regulation in the context of transitions between cellular states.
Bibliography: p. 267-287