AUTHOR=He Jiahui , Ruan Wenhao , Sun Jieli , Wang Fang , Yan Wenjuan 

TITLE=Functional Characterization of c-di-GMP Signaling-Related Genes in the Probiotic Lactobacillus acidophilus

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01935

DOI=10.3389/fmicb.2018.01935

ISSN=1664-302X

ABSTRACT=<p>The bacterial second messenger cyclic diguanylate monophosphate (c-di-GMP) regulates a series of cellular functions, including biofilm formation, motility, virulence, and other processes. In this study, we confirmed the presence of several c-di-GMP related genes and evaluated their activities and functions in <italic>Lactobacillus</italic> species. Bioinformatic and biochemical analyses revealed that <italic>Lactobacillus acidophilus</italic> La-14 have an active c-di-GMP phosphodiesterase (PdeA) that may act in the metabolic cycle of c-di-GMP. A GGDEF protein (DgcA) induced two c-di-GMP-dependent phenotypes (low motility and high production of curli fimbriae) in <italic>Escherichia coli</italic> by heterologously expressed <italic>in vivo</italic> but showed no diguanylate cyclases activity <italic>in vitro</italic> while in the expression without the N-terminal transmembrane domain. The degenerated EAL-domain protein (PdeB), encoded by the last gene in the <italic>gts</italic> operon, serve as a c-di-GMP receptor which may be associated with exopolysaccharide (EPS) synthesis in <italic>L. acidophilus</italic>. Heterologously expressed GtsA and GtsB, encoded by the <italic>gts</italic> operon, stimulated EPS and biofilm formation in <italic>E. coli</italic> BL21. Constitutive expression in <italic>L. acidophilus</italic> revealed that a high concentration of intracellular DgcA levels increased EPS production in <italic>L. acidophilus</italic> and enhanced the co-aggregation ability with <italic>E. coli</italic> MG1655, which may be beneficial to the probiotic properties of <italic>Lactobacillus</italic> species. Our study imply that the c-di-GMP metabolism-related genes, in <italic>L. acidophilus</italic>, work jointly to regulate its functions in EPS formation and co-aggregation.</p>