Salmonella biofilms: An overview on occurrence, structure, regulation and eradication

TLDR: Insight into the pathogen's complex biofilm process will eventually lead to further unraveling of its intricacies and more efficient strategies to combat Salmonella biofilms, as well as the potential of combination therapy.

About: This article is published in Food Research International.The article was published on 2012-03-01 and is currently open access. It has received 421 citations till now. The article focuses on the topics: Biofilm & Salmonella.

Figures

Table 2 Representation of all 19 S. Typhimurium GGDEF and EAL domain proteins.

Table 1 Most important and already experimentally validated structural determinants important for Salmonella biofilm formation on particular surfaces.

Fig. 1. Complex regulatory network governing Salmonella biofilm formation. Working model for the regulation of Salmonella biofilm formation. Arrows and flat-headed arrows represent an activating and repressing effect respectively. Broken lines indicate putative links, that need to be experimentally validated or further investigated. ‘P’ symbols represent transferable phosphorus groups of two component systems. Light blue rectangles represent the genomic organization of the genes encoding the major structural biofilm components, indicated by orange rectangles. The orange ‘Motility’ rectangle is an exception as it represents a community behaviour related to biofilm formation (regulated through flagellar genes (dark green circles) and flagella (green rectangle)). Light blue circles represent important regulators involved in the production of the major structural biofilm components. Light green circles, triangles and rectangles represent global trans-acting regulators, the Crl protein and sRNAs, respectively, and lightning bolt symbols represent the input and integration of different environmental signals through these general regulators into the regulatory system. Orange circles and arrows indicate the link between PhoPQ and biofilm formation. The grey and purple circles indicate the role of metabolism and quorum sensing respectively. Dark blue and red circles represent EAL and GGDEF proteins, respectively, involved in c-di-GMP turnover, of which the exact functions can be found throughout the text and in Table 2. Red rectangles represent the different, but interconnected c-di-GMP pools. CsgD is the general Salmonella biofilm regulator (Gerstel et al., 2003), as can be seen in the right-hand side of the figure, triggering the biosynthesis of the major extracellular matrix components consisting of a proteinaceous fractionmade up by curli fimbriae (Römling, Bian, et al., 1998) and the large secreted BapA protein (Latasa et al., 2005) on the one hand, and a exopolysaccharide fraction largely made up by cellulose (Zogaj et al., 2001) and an O-antigenic capsule (O-Ag-capsule) (Gibson et al., 2006) on the other hand. Cellulose synthesis is not only regulated by CsgD, via AdrA and c-di-GMP (Simm et al., 2004; Zakikhany et al., 2010; Zogaj et al., 2001), but also via a CsgD-independent pathway in which STM1987 (and other GGDEF proteins) and c-di-GMP are involved (Da Re & Ghigo, 2006; Garcia et al., 2004; Simm et al., 2007; Solano et al., 2002). From the complex regulation of the c-di-GMP network, on the left-hand side of the figure, it becomes clear that different c-di-GMP pools exist within Salmonella cells. These different, but interconnected, pools serve slightly different, but intertwined, purposes (Simm et al., 2007; Solano et al., 2009), as clarified throughout the text.

Frequently asked questions

Q1. What have the authors contributed in "Salmonella biofilms: an overview on occurrence, structure, regulation and eradication" ?

A detailed overview of the current knowledge of the structural organization as well as the complex regulation of Salmonella biofilm formation is given in this paper. 

Q2. What was previously shown not to be involved in virulence?

another important constituent of the extracellular matrix, was previously also shown not to be involved in virulence (Solano et al., 2002). 

Q3. Why was the homologous STM4261 found not to be important?

The highly homologous STM4261 (siiE), together with BapAencoding the two largest proteins in the Salmonella genome, was found not to be important during S. Enteritidis biofilm formation, maybe because of functional redundancy between SiiE and BapA (Latasa et al., 2005). 

Q4. What is the advantage of top-down screening?

An advantage of top-down screening is that stringent selection criteria regarding the range of application of the compounds (range of active concentrations, temperature range, range of substrate materials, preventive effect vs. destructive effect, etc.) can be applied. 

Q5. What are the bioactive compounds in grapefruit juice?

Grapefruit juice contains bioactive compounds such as furocoumarins, carotenoids,flavanoids, limonoids, pectin andvitaminC,whichhave shown to confer several health benefits. 

Q6. What is the role of OmpR in the csgD promoter?

OmpR is part of the EnvZ (membranebound sensor kinase)/OmpR two-component regulatory system able to change the OmpR phosphorylation pattern in response to environmental changes such as osmolarity (high osmolarity leads to high levels of phosphorylated OmpR (OmpR-P)) and pH. Several OmpR binding sites (D1–D7) in the cgsD promoter were identified using a combination of response genetic studies and in vitro experiments (gel shifts and DNase The authorfootprints) (Gerstel, Kolb, & Römling, 2006; Gerstel, Park, & Römling, 2003), showing similarities to the well-characterized ompF promoter (Huang & Igo, 1996). 

Q7. What is the role of the matrix in the resistance to triclosan?

The higher resistance of biofilm-associated cells as compared to biofilm-derived cells suggests that the matrix also plays a significant role in the resistance against triclosan. 

Q8. What is the recent technique used to visualize bacterial biofilms?

Recent microscopic techniques such as e.g. episcopic differential interference contrast microscopy coupled to epifluorescence allowed proper in situ visualization of bacterial biofilms, as exemplified by the detection of S. Thompson on lettuce leaves (Warner, Rothwell, & Keevil, 2008). 

Q9. How much of the rpoS regulon is up-regulated in biofilm?

Hamilton et al. showed via microarray analysis that more than 25% of the S. Typhimurium RpoS regulon is up-regulated in biofilm cells on silicone rubber (Hamilton et al., 2009). 

Q10. Why was the rdar morphotype observed in a daily passage regimen?

Since this phenomenon was observed independent of the presence of a functional csgD (and hence rdar morphotype) in a daily passage regimen (including stationary phase), it was concluded that this is because of a benefit in nutrient scavenging. 

Q11. What is the top-down approach to biofilm-specific inhibitors?

In the top-down approach, libraries of chemical compounds and natural product analogues are screened for compounds that are able to prevent or eradicate biofilm formation. 

Q12. What was the reason for the patchy biofilm distribution on gallstones?

Using this new model system, it also became clear that the patchy, surface specific biofilm distribution on gallstones was due to local differences in cholesterol distribution and that bile also induced the biofilm formation on cholesterol. 

Q13. What is the role of glucose in the development of biofilm inhibitors?

This hypothesis was confirmed by the finding that glucose leads to inhibition of the rdar morphotype, suggesting that gluconeogenesis may be a good target in the development of biofilm inhibitors against a wide variety of bacteria. 

Q14. What is the role of cellulose in the attachment of parsley to leaves?

together with curli, also play a role during the transfer of contaminated water to the edible parts of parsley (Lapidot & Yaron, 2009), while it was shown not to be involved in the initial attachment properties of S. Typhimurium to parsley (Lapidot et al., 2006). 

Q15. What is the biofilm formation capacity of the fimbrial and curli mutants?

plasmidencoded fimbrial (pef) and curli (csg) mutants are defective for biofilm formation on plastic, HEp-2 cells and chicken intestinal tissue.