cyclic-gmp and Rodent-Diseases

Topics: Animals; Animals, Newborn; Calmodulin; Cyclic GMP; Disease Models, Animal; Dog Diseases; Dogs; Mice; Mice, Neurologic Mutants; Mutation; Nervous System Malformations; Phosphoric Diester Hydrolases; Photoreceptor Cells; Retina; Retinal Degeneration; Rodent Diseases

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cattle; Cyclic GMP; Dog Diseases; Dogs; Guanosine Triphosphate; Guanylate Cyclase; Hydrolysis; Mice; Mice, Mutant Strains; Phosphoproteins; Photoreceptor Cells; Rabbits; Rats; Retina; Retinal Degeneration; Rod Cell Outer Segment; Rodent Diseases

Biofilms contribute to Pseudomonas aeruginosa persistence in a variety of diseases, including cystic fibrosis, burn wounds, and chronic suppurative otitis media. However, few studies have directly addressed P. aeruginosa biofilms in vivo. We used a chinchilla model of otitis media, which has previously been used to study persistent Streptococcus pneumoniae and Haemophilus influenzae infections, to show that structures formed in vivo are biofilms of bacterial and host origin within a matrix that includes Psl, a P. aeruginosa biofilm polysaccharide. We evaluated three biofilm and/or virulence mediators of P. aeruginosa known to affect biofilm formation in vitro and pathogenesis in vivo--bis-(3',5')-cyclic dimeric GMP (c-di-GMP), flagella, and quorum sensing--in a chinchilla model. We show that c-di-GMP overproduction has a positive impact on bacterial persistence, while quorum sensing increases virulence. We found no difference in persistence attributed to flagella. We conclude from these studies that a chinchilla otitis media model provides a means to evaluate pathogenic mediators of P. aeruginosa and that in vitro phenotypes should be examined in multiple infection systems to fully understand their role in disease.

Topics: Animals; Biofilms; Chinchilla; Chronic Disease; Cyclic GMP; Disease Models, Animal; Gene Expression Regulation, Bacterial; Humans; Otitis Media; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Rodent Diseases; Virulence

HD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria. Borrelia burgdorferi possesses a single set of c-di-GMP-metabolizing enzymes, including a putative HD-GYP domain protein, BB0374. Recently, we characterized the EAL domain phosphodiesterase PdeA. A mutation in pdeA resulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with a K(m) of 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing the pdeA pdeB double mutant, we demonstrate that no additional phosphodiesterases are present in B. burgdorferi. pdeB single mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing a pilZ pdeB double mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly in pdeB mutant cells, these cells exhibited a reduced ability to survive in Ixodes scapularis ticks. Consequently, those ticks were unable to transmit the infection to naïve mice. All of these phenotypes were restored when the mutant was complemented. Identification of this role of pdeB increases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle of B. burgdorferi.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Borrelia burgdorferi; Cyclic GMP; Disease Models, Animal; Female; Gene Deletion; Genetic Complementation Test; Ixodes; Kinetics; Locomotion; Lyme Disease; Mice; Mice, Inbred C3H; Rodent Diseases; Virulence

Topics: Animals; Cyclic GMP; Disease Models, Animal; Dog Diseases; Dogs; Mice; Mice, Mutant Strains; Mutation; Nucleotides, Cyclic; Phosphoric Diester Hydrolases; Retina; Retinal Degeneration; Rodent Diseases

Wriggle mouse Sagami (WMS), a newly discovered BALB/C mouse strain, is characterized by its locomotor instability, abnormal gait pattern and neck wriggling. Although the growth of WMS mice is delayed, compared with normal BALB/C mice, the brain size corresponds to the relatively smaller body weight. In gross or histological examinations no local atrophy appears in the cerebrum, cerebellum, brain stem or spinal cord. The c-GMP level in the WMS cerebellum is decreased, but the c-AMP level is normal. The ataxic gait is not improved significantly by the administration of thyrotropin releasing hormone (TRH). These results indicate that the mechanism inducing ataxia and abnormal gait pattern in WMS may be different from those in other genetically-determined ataxic mice, e. g., Rolling mouse Nagaya (RMN), PCD, Staggerer and Reeler.

Topics: Animals; Ataxia; Body Weight; Brain; Brain Stem; Cerebellum; Cyclic AMP; Cyclic GMP; Mice; Mice, Inbred BALB C; Mice, Neurologic Mutants; Organ Size; Rodent Diseases; Spinal Cord