Initial cyclic-di-GMP upregulation triggers sporadic cellular expansion leading to improved cellular survival.

Bacterial second messenger c-di-GMP upregulation is associated with the transition from planktonic to sessile microbial lifestyle, inhibiting cellular motility, and virulence. However, in-depth elucidation of the cellular processes resulting from c-di-GMP upregulation has not been fully explored. Here, we report the role of upregulated cellular c-di-GMP in promoting planktonic cell growth of Escherichia coli K12 and Pseudomonas aeruginosa PAO1. We found a rapid expansion of cellular growth during initial cellular c-di-GMP upregulation, resulting in a larger planktonic bacterial population. The initial increase in c-di-GMP levels promotes bacterial swarming motility during the growth phase, which is subsequently inhibited by the continuous increase of c-di-GMP, and ultimately facilitates the formation of biofilms. We demonstrated that c-di-GMP upregulation triggers key bacterial genes linked to bacterial growth, swarming motility, and biofilm formation. These genes are mainly controlled by the master regulatory genes csgD and csrA. This study provides us a glimpse of the bacterial behavior of evading potential threats through adapting lifestyle changes via c-di-GMP regulation.

Caffeic acid phenethyl ester, a coffee polyphenol, inhibits DNA methylation in vitro and in vivo.

DNA methylation represents an important epigenetic regulation of the genome. Earlier studies have suggested that dietary phenolic compounds including those contained in coffee, tea and soy products may modulate the level of DNA methylation. In this study, we first characterize the effect of caffeic acid phenethyl ester (CAPE) and other dietary phenolic compounds on DNA methylation in vitro. The IC50 values of CAPE, daidzein, isorhamnetin and genistein are 7.6, 6.9, 6.2, and 4.3 µM, respectively, in an in-vitro enzymatic assay system. Computational analysis indicates that CAPE, daidzein, isorhamnetin and genistein can bind inside the DNA substrate-binding site in human DNMT1 with a favorable binding energy. In an animal study, we find that maternal CAPE treatment shifts the coat color distribution of the 21-day-old Avy/a offspring towards the yellow phenotype, indicating that CAPE inhibits the methylation of the agouti gene promoter sequence in vivo. The results from this study may shed light on the potential epigenetic effect in the offspring resulting from maternal intake of certain coffee phenolics during pregnancy.

Advances in Bacterial Biofilm Management for Maintaining Microbiome Homeostasis.

Certain microbial biofilm in the human-microbiota community can negatively impact the host microbiome. This gives rise to various methods to prevent the formation of biofilms or to facilitate biofilm dispersal from surfaces and tissues in the host. Despite all these efforts, these persistent microbial biofilms on surfaces and in the host tissue can result in health problems to the host and its microbiome. It is the adaptive behavior of microbes within the biofilm that confers on these tenacious microbes the resistance to harsh environments, antibiotic treatments, and the ability to evade the host immune system. In this review, the approaches to combat microbial biofilm in the last decade are discussed. The biochemical pathway regulating biofilm formation is first discussed, followed by the discussion of the three approaches to combat biofilm formation: physical, chemical, and biological approaches. The advances in these approaches have given rise to methods of effectively dispersing the microbial biofilm and preventing the adherence of these microbial communities altogether. As there are numerous approaches to target biofilm, in this review the attempt is to provide insights on how these approaches have been used to modulate the host-microbiome by looking at the individual strengths and weaknesses.