Melissa Sivaneson

Imperial College London, London, ENG, United Kingdom

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Publications (2)11.2 Total impact

  • Source
    Helga Mikkelsen, Melissa Sivaneson, Alain Filloux
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    ABSTRACT: Biofilm formation in P. aeruginosa is a highly regulated process that proceeds through a number of distinct stages. This development is controlled by a wide range of factors, of which two-component systems (TCSs) play a key role. In this review, we focus on some of the TCSs that regulate the switch from a motile to a sessile bacterial lifestyle, either via the production of extracellular appendages or by the production of exopolysaccharides. Extracellular appendages, such as flagella, type IV pili and Cup fimbriae are often involved in the initial attachment of bacteria to a surface. In P. aeruginosa, many of these surface structures are regulated by TCSs, and some systems regulate more than one type of appendage. Furthermore, the production of exopolysaccharides, such as Pel and Psl, is required for P. aeruginosa biofilm formation. The regulation of Pel and Psl is post-transcriptionally repressed by RsmA, the activity of which is controlled by a complex regulatory system involving several sensor kinases and accessory components. Furthermore, the Rsm system is a major control system that inversely regulates factors involved in motility and acute infection on one hand, and factors involved in biofilm formation and chronic infection on the other hand. Finally, a series of TCSs has recently been discovered that regulates biofilm development in a stage-specific manner. Taken together, these complex regulatory networks allow the bacterium to respond appropriately to diverse environmental stimuli, and increased knowledge of their mechanisms and signals could be of great importance in the design of novel antibacterial strategies.
    Environmental Microbiology 05/2011; 13(7):1666-81. · 6.24 Impact Factor
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    ABSTRACT: Pseudomonas aeruginosa is responsible for chronic and acute infections in humans. Chronic infections are associated with production of fimbriae and the formation of a biofilm. The two-component system Roc1 is named after its role in the regulation of cup genes, which encode components of a machinery allowing assembly of fimbriae. A non-characterized gene cluster, roc2, encodes components homologous to the Roc1 system. We show that cross-regulation occurs between the Roc1 and Roc2 signalling pathways. We demonstrate that the sensors RocS2 and RocS1 converge on the response regulator RocA1 to control cupC gene expression. This control is independent of the response regulator RocA2. Instead, we show that these sensors act via the RocA2 response regulator to repress the mexAB-oprM genes. These genes encode a multidrug efflux pump and are upregulated in the rocA2 mutant, which is less susceptible to antibiotics. It has been reported that in cystic fibrosis lungs, in which P. aeruginosa adopts the biofilm lifestyle, most isolates have an inactive MexAB-OprM pump. The concomitant RocS2-dependent upregulation of cupC genes (biofilm formation) and downregulation of mexAB-oprM genes (antibiotic resistance) is in agreement with this observation. It suggests that the Roc systems may sense the environment in the cystic fibrosis lung.
    Molecular Microbiology 03/2011; 79(5):1353-66. · 4.96 Impact Factor

Publication Stats

64 Citations
11.20 Total Impact Points

Institutions

  • 2011
    • Imperial College London
      • Division of Cell and Molecular Biology
      London, ENG, United Kingdom