Nucleotide Second Messenger-Based Signaling in Extreme Acidophiles of the Acidithiobacillus Species Complex: Partition Between the Core and Variable Gene Complements

Abstract

Cyclic and linear nucleotides are key elements of the signal transduction networks linking perception of the environment to specific cellular behavior of prokaryotes. These molecular mechanisms are particularly important in bacteria exposed to different, and frequently simultaneous, types of extreme conditions. This is the case in acidithiobacilli, a group of extremophilic bacteria thriving in highly acidic biotopes, that must also cope with significant variations in temperature, osmotic potentials and concentrations of various transition metals and metalloids. Environmental cues sensed by bacteria are transduced into differential levels of nucleotides acting as intracellular second messengers, promoting the activation or inhibition of target components and eliciting different output phenotypes. Cyclic (c) di-GMP, one of the most common bacterial second messengers, plays a key role in lifestyle changes in many bacteria, including acidithiobacilli. The presence of functional c-di-GMP-dependent signal transduction pathways in representative strains of the best-known linages of this species complex has been reported. However, a comprehensive panorama of the c-di-GMP modulated networks, the cognate input signals and output responses, are still missing for this group of extremophiles. Moreover, little fundamental understanding has been gathered for other nucleotides acting as second messengers. Taking advantage of the increasing number of sequenced genomes of the taxon, here we address the challenge of disentangling the nucleotide-driven signal transduction pathways in this group of polyextremophiles using comparative genomic tools and strategies. Results indicate that the acidithiobacilli possess all the genetic elements required to establish functional transduction pathways based in three different nucleotide-second messengers: (p)ppGpp, cyclic AMP (cAMP), and c-di-GMP. The elements related with the metabolism and transduction of (p)ppGpp and cAMP appear highly conserved, integrating signals related with nutrient starvation and polyphosphate metabolism, respectively. In contrast, c-di-GMP networks appear diverse and complex, differing both at the species and strain levels. Molecular elements of c-di-GMP metabolism and transduction were mostly found scattered along the flexible genome of the acidithiobacilli, allowing the identification of probable control modules that could be critical for substrate colonization, biofilm development and intercellular interactions. These may ultimately convey increased endurance to environmental stress and increased potential for gene sharing and adaptation to changing conditions.

Biofilms: The Microbial “Protective Clothing” in Extreme Environments

“…Nucleotides such as cyclic dimeric guanosine 3′,5′-monophosphate (c-di-GMP), cyclic adenosine 3′,5′-monophosphate (cAMP), etc., are critical elements of the signal transduction networks, which link perceptions of the environment to the specific cellular behaviors of prokaryotes (Table 1). These molecular mechanisms are particularly crucial in microorganisms that are exposed to certain types of extreme environments [145].…”

“…Generally, an increased concentration of intracellular c-di-GMP promotes surface attachment and biofilm formation, while decreased intracellular c-di-GMP concentration induces biofilm dispersal [152] (Table 1). In some acidophiles, c-di-GMP signaling is related to biofilm formation [145]. For example, Acidithiobacillus can thrive in extreme environments with poor nutrients, high concentrations of heavy metals, and extreme acidity.…”

Evolution of Predicted Acid Resistance Mechanisms in the Extremely Acidophilic Leptospirillum Genus

“…In other organisms, the GGDEF domain is involved in cyclic diguanosine monophosphate turnover and the production of the secondary messenger C-di-GMP (reviewed in [110]). A functional GGDEF gene was reported in the extremely acidophilic genus Acidithiobacillus, although it was associated with the EAL rather than the GAF domains [111,112]. The secondary messenger C-di-GMP was implicated in the regulation of biofilm formation and other functions in many bacteria [113].…”

Quorum Sensing Signaling Molecules Positively Regulate c-di-GMP Effector PelD Encoding Gene and PEL Exopolysaccharide Biosynthesis in Extremophile Bacterium Acidithiobacillus thiooxidans

“…Interestingly, Prescott and Decho [ 54 ] have proposed the orphan QS transcriptional regulators as key molecular players for flexibility and adaptability of QS, especially to maintain or develop cell-cell communication during the dynamic evolution of a biofilm community. Indeed, a bioinformatic analysis of the new available genome sequence on ten different genome sequences also revealed that A. thiooxidans and A. caldus possess several copies of the fleQ gene [ 57 ]. Then, a possible mechanism of action of the 3-oxo-C8-AHL could be promotion of transcription of a FleQ encoding gene, which in turn could induce PEL exopolysaccharide biosynthesis, as occurs in P .…”