The Escherichia coli MarA protein regulates the ycgZ‐ymgABC operon to inhibit biofilm formation

Kettles, Rachel A.; Tschowri, Natalia; Lyons, Kevin J; Sharma, Prateek; Hengge, Regine; Webber, Mark A.; Grainger, David C.

doi:10.1111/mmi.14386

Cited by 18 publications

(17 citation statements)

References 64 publications

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“…As OmpF plays an important role in the influx of antibiotics, the bacterium thus controls the efflux and influx of antibiotics by activating AcrAB-TolC and abolishing OmpF production, respectively. Interestingly, while MarA upregulates pump production, it downregulates biofilm formation through activation of the ycgZ-ymgABC operon which eventually reduces curli formation [ 161 ]. Possibly, MarA helps to activate a mechanism for cells to escape from biofilms as defence to the antibiotic insult.…”

Section: Mechanisms Of Biofilm Recalcitrancementioning

confidence: 99%

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

et al. 2020

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Multidrug resistant bacteria are a global threat for human and animal health. However, they are only part of the problem of antibiotic failure. Another bacterial strategy that contributes to their capacity to withstand antimicrobials is the formation of biofilms. Biofilms are associations of microorganisms embedded a self-produced extracellular matrix. They create particular environments that confer bacterial tolerance and resistance to antibiotics by different mechanisms that depend upon factors such as biofilm composition, architecture, the stage of biofilm development, and growth conditions. The biofilm structure hinders the penetration of antibiotics and may prevent the accumulation of bactericidal concentrations throughout the entire biofilm. In addition, gradients of dispersion of nutrients and oxygen within the biofilm generate different metabolic states of individual cells and favor the development of antibiotic tolerance and bacterial persistence. Furthermore, antimicrobial resistance may develop within biofilms through a variety of mechanisms. The expression of efflux pumps may be induced in various parts of the biofilm and the mutation frequency is induced, while the presence of extracellular DNA and the close contact between cells favor horizontal gene transfer. A deep understanding of the mechanisms by which biofilms cause tolerance/resistance to antibiotics helps to develop novel strategies to fight these infections.

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Section: Mechanisms Of Biofilm Recalcitrancementioning

confidence: 99%

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

et al. 2020

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“…This suggests that the end biofilm deficit is a result of repression of curli biosynthesis in response to loss of efflux function (Baugh et al, 2012). One theory is that MarA regulates biofilm formation through binding upstream of the ycgZ-ymgABC operon, which has a role in curli formation (Kettles et al, 2019).…”

Section: Biofilms and Stressmentioning

confidence: 99%

MarA, RamA, and SoxS as Mediators of the Stress Response: Survival at a Cost

Holden

Webber

2020

Front. Microbiol.

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To survive and adapt to changing environments, bacteria have evolved mechanisms to express appropriate genes at appropriate times. Exposure to antimicrobials triggers a global stress response in Enterobacteriaceae, underpinned by activation of a family of transcriptional regulators, including MarA, RamA, and SoxS. These control a program of altered gene expression allowing a rapid and measured response to improve fitness in the presence of toxic drugs. Increased expression of marA, ramA, and soxS up regulates efflux activity to allow detoxification of the cell. However, this also results in trade-offs in other phenotypes, such as impaired growth rates, biofilm formation and virulence. Here, we review the current knowledge regarding the trade-offs that exist between drug survival and other phenotypes that result from induction of marA, ramA, and soxS. Additionally, we present some new findings linking expression of these regulators and biofilm formation in Enterobacteriaceae, thereby demonstrating the interconnected nature of regulatory networks within the cell and explaining how trade-offs can exist between important phenotypes. This has important implications for our understanding of how bacterial virulence and biofilms can be influenced by exposure to antimicrobials.

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“…In addition, the stress response regulator marR 38 and the 23S rRNA methyltransferase rlmI 39 were both found to be beneficial for biofilm fitness at the 12 hour time point only, and reduced biofilm biomass was found in deletion mutants (figure 3a). These genes have both previously been implicated in biofilm formation [39][40][41] , but the effect on early biofilm formation has not been described previously.…”

Section: Regulatory Genes Are Important In the Early Biofilmmentioning

confidence: 95%

Massively parallel transposon mutagenesis identifies temporally essential genes for biofilm formation inEscherichia coli

Holden

Yasir

Turner

et al. 2020

Preprint

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Biofilms complete a life cycle where cells aggregate, grow and produce a structured community before dispersing to seed biofilms in new environments. Progression through this life cycle requires controlled temporal gene expression to maximise fitness at each stage. Previous studies have focused on the essential genome for the formation of a mature biofilm, but here we present an insight into the genes involved at different stages of biofilm formation. We used TraDIS-Xpress; a massively parallel transposon mutagenesis approach using transposon-located promoters to assay expression of all genes in the genome. We determined how gene essentiality and expression affects the fitness of E. coli growing as a biofilm on glass beads after 12, 24 and 48 hours. A selection of genes identified as important were then validated independently by assaying biofilm biomass, aggregation, curli biosynthesis and adhesion ability of defined mutants. We identified 48 genes that affected biofilm fitness including genes with known roles and those not previously implicated in biofilm formation. Regulation of type 1 fimbriae and motility were important at all time points. Adhesion and motility were important for the early biofilm, whereas matrix production and purine biosynthesis were only important as the biofilm matured. We found strong temporal contributions to biofilm fitness for some genes including some which were both beneficial and detrimental depending on the stage at which they are expressed, including dksA and dsbA. Novel genes implicated in biofilm formation included ychM and truA involved in cell division, crfC and maoP in DNA housekeeping and yigZ and ykgJ of unknown function. This work provides new insights into the requirements for successful biofilm formation through the biofilm life cycle and demonstrates the importance of understanding expression and fitness through time.

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The Escherichia coli MarA protein regulates the ycgZ‐ymgABC operon to inhibit biofilm formation

Cited by 18 publications

References 64 publications

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

MarA, RamA, and SoxS as Mediators of the Stress Response: Survival at a Cost

Massively parallel transposon mutagenesis identifies temporally essential genes for biofilm formation inEscherichia coli

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