The c‐di‐AMP signaling system influences stress tolerance and biofilm formation of Streptococcus mitis

Abstract

Streptococcus mitis is a commensal bacterial species of the oral cavity, with the potential for opportunistic pathogenesis. For successful colonization, S. mitis must be able to adhere to surfaces of the oral cavity and survive and adapt to frequently changing environmental conditions. Cyclic‐di‐AMP (c‐di‐AMP) is a nucleotide second messenger, involved in the regulation of stress responses and biofilm formation in several bacterial species. Cyclic‐di‐AMP is produced by diadenylate cyclases and degraded by phosphodiesterases. We have previously shown that in S. mitis , one diadenylate cyclase (CdaA) and at least two phosphodiesterases (Pde1 and Pde2) regulate the intracellular concentration of c‐di‐AMP. In this study, we utilized S. mitis deletion mutants of cdaA , pde1 , and pde2 to analyze the role of c‐di‐AMP signaling in various stress responses, biofilm formation, and adhesion to eukaryotic cells. Here, we demonstrate that the Δ pde1 mutant displayed a tendency toward increased susceptibility to acetic acid at pH 4.0. Deletion of cdaA increases auto‐aggregation of S. mitis but reduces biofilm formation on an abiotic surface. These phenotypes are more pronounced under acidic extracellular conditions. Inactivation of pde1 or pde2 reduced the tolerance to ciprofloxacin, and UV radiation and the Δ pde1 mutant was more susceptible to Triton X‐100, indicating a role for c‐di‐AMP signaling in responses to DNA damage and cell membrane perturbation. Finally, the Δ pde2 mutant displayed a tendency toward a reduced ability to adhere to oral keratinocytes. Taken together, our results indicate an important role for c‐di‐AMP signaling in cellular processes important for colonization of the mouth.

Near‐infrared light-triggered nitric oxide nanocomposites for photodynamic/photothermal complementary therapy against periodontal biofilm in an animal model

“…In groups with aPTT effects (Ag 2 S+NIR and Ag 2 S@ZIF-90+NIR) , the expression of pgn 0523, pgn 1187, pgn 2003 and pgn 0521 was almost identical to that of the control group ( Figure 6 B ). It was reported that the CFU counts of the mutant lacking c-di-AMP synthetase and lacking c-di-AMP hydrolase of Streptococcus mitis were not different from that of wild-type (WT) at 52 °C, demonstrating that there were scarcely any effects of temperature alteration on c-di-AMP expression 48 . In the Ag 2 S@ZIF-90/ICG+NIR group, the expression level of pgn 0523 was approximately 3-fold higher than that of the control since biofilms enhance the response to ROS pressure by synthesizing larger amounts of c-di-AMP.…”

“…Changes in the concentrations of c-di-AMP could alter bacterial pathogenicity in mouse models and thus participate in the regulation of virulence in vivo 51 , 52 . In addition, several receptors of the innate immune system can recognize c-di-AMP, which induces NF-κB activation or type I interferon production 17 , 48 . This was also demonstrated by in vitro experiments simulating inflammation caused by biofilm infection ( Figure S23 ).…”

Adaptation ofListeria monocytogenesto perturbation ofc‐di‐AMPmetabolism underpins its role in osmoadaptation and identifies a fosfomycin uptake system

“…Several studies revealed that perturbation of c‐di‐AMP metabolism affects the formation of biofilms by B . subtilis and Streptococci (Gundlach et al ., 2016; Fahmi et al ., 2019; The et al ., 2019; Faozia et al ., 2021; Rorvik et al ., 2021). Here, we show that the cellular levels of c‐di‐AMP influence biofilm formation by L .…”

Soil-derived Streptomyces sp. GMR22 producing antibiofilm activity against Candida albicans: bioassay, untargeted LC-HRMS, and gene cluster analysis

“…Another important molecule in biofilm formation is cyclic-di-AMP [ 23 ]. As a nucleotide second messenger, C-di-AMP aids in regulating stress responses and forming biofilm in a variety of microbial species [ 24 ]. The accumulation of C-di-AMP influences a myriad of gene expression including the two major operons integral in biofilm formation [ 25 ].…”