1-Undecene from Pseudomonas aeruginosa is an olfactory signal for flight-or-fight response in Caenorhabditis elegans.

Animals possess conserved mechanisms to detect pathogens and to improve survival in their presence by altering their own behavior and physiology. Here, we utilize Caenorhabditis elegans as a model host to ask whether bacterial volatiles constitute microbe-associated molecular patterns. Using gas chromatography-mass spectrometry, we identify six prominent volatiles released by the bacterium Pseudomonas aeruginosa. We show that a specific volatile, 1-undecene, activates nematode odor sensory neurons inducing both flight and fight responses in worms. Using behavioral assays, we show that worms are repelled by 1-undecene and that this aversion response is driven by the detection of this volatile through AWB odor sensory neurons. Furthermore, we find that 1-undecene odor can induce immune effectors specific to P. aeruginosa via AWB neurons and that brief pre-exposure of worms to the odor enhances their survival upon subsequent bacterial infection. These results show that 1-undecene derived from P. aeruginosa serves as a pathogen-associated molecular pattern for the induction of protective responses in C. elegans.

Barium titanate microparticles as potential carrier platform for lanthanide radionuclides for their use in the treatment of arthritis.

Since the inception of radiation synovectomy, a host of radioactive colloids and microparticles incorporating suitable therapeutic radionuclides have been proposed for the treatment of arthritis. The present article reports the synthesis and evaluation of barium titanate microparticles as an innovative and effective carrier platform for lanthanide radionuclides in the preparation of therapeutic agents for treatment of arthritis. The material was synthesized by mechanochemical route and characterized by X-ray diffraction, scanning electron microscopy, surface area, and particle size distribution analyses. Loading of lanthanide radionuclides (166 Ho, 153 Sm, 177 Lu, and 169 Er) on the microparticles was achieved in high yield (> 95%) resulting in the formulation of loaded particulates with excellent radiochemical purities (> 99%). Radiolanthanide-loaded microparticles exhibited excellent in vitro stability in human serum. In vitro diethylene triamine pentaacetic acid challenge study indicated fairly strong chemical association of lanthanides with barium titanate microparticles. Long-term biodistribution studies carried out after administration of 177 Lu-loaded microparticles into one of the knee joints of normal Wistar rats revealed near-complete retention of the formulation (> 96% of the administered radioactivity) within the joint cavity even 14 days post-administration. The excellent localization of the loaded microparticles was further confirmed by sequential whole-body radio-luminescence imaging studies carried out using 166 Ho-loaded microparticles.

Foraging Signals Promote Swarming in Starving Pseudomonas aeruginosa.

The opportunistic human pathogen Pseudomonas aeruginosa is known for exhibiting diverse forms of collective behaviors, like swarming motility and biofilm formation. Swarming in P. aeruginosa is a collective movement of the bacterial population over a semisolid surface, but specific swarming signals are not clear. We hypothesize that specific environmental signals induce swarming in P. aeruginosa. We show that under nutrient-limiting conditions, a low concentration of ethanol provides a strong ecological motivation for swarming in P. aeruginosa strain PA14. Ethanol serves as a signal and not a source of carbon under these conditions. Moreover, ethanol-driven swarming relies on the ability of the bacteria to metabolize ethanol to acetaldehyde using a periplasmic quinoprotein alcohol dehydrogenase, ExaA. We found that ErdR, an orphan response regulator linked to ethanol oxidation, is necessary for the transcriptional regulation of a cluster of 17 genes, including exaA, during swarm lag. Further, we show that P. aeruginosa displays characteristic foraging motility on a lawn of Cryptococcus neoformans, a yeast species, in a manner dependent on the ethanol dehydrogenase ErdR and on rhamnolipids. Finally, we show that ethanol, as a volatile, could induce swarming in P. aeruginosa at a distance, suggesting long-range spatial effects of ethanol as a signaling molecule. IMPORTANCE P. aeruginosa, a Gram-negative opportunistic pathogen, can adapt to diverse ecological niches and exhibits several forms of social behavior. Swarming (flagellum-driven collective motility) is a collective behavior of P. aeruginosa exclusively over semisolid surfaces. However, the ecological motivations for swarming are not known. Here, we demonstrate the importance of a specific environmental cue, ethanol, produced by many microbes, in inducing swarming in the P. aeruginosa population during starvation. We show that ethanol is a signal for swarming in P. aeruginosa. Our study provides a framework to understand swarming as a chemotactic response of bacterium to a food source via a foraging signal, ethanol.

Context-Specific Requirement of Forty-Four Two-Component Loci in Pseudomonas aeruginosa Swarming.

Swarming in Pseudomonas aeruginosa is a coordinated movement of bacteria over semisolid surfaces (0.5%-0.7% agar). On soft agar, P. aeruginosa exhibits a dendritic swarm pattern, with multiple levels of branching. However, the swarm patterns typically vary depending upon the experimental design. In the present study, we show that the pattern characteristics of P. aeruginosa swarm are highly environment dependent. We define several quantifiable, macroscale features of the swarm to study the plasticity of the swarm, observed across different nutrient formulations. Furthermore, through a targeted screen of 113 two-component system (TCS) loci of the P. aeruginosa strain PA14, we show that forty-four TCS genes regulate swarming in PA14 in a contextual fashion. However, only four TCS genes-fleR, fleS, gacS, and PA14_59770-were found essential for swarming. Notably, many swarming-defective TCS mutants were found highly efficient in biofilm formation, indicating opposing roles for many TCS loci.