The Effects of a Bacterial Endotoxin on Behavior and Sensory-CNS-Motor Circuits in Drosophila melanogaster

Abstract

The effect of bacterial sepsis on animal behavior and physiology is complex due to direct and indirect actions. The most common form of bacterial sepsis in humans is from gram-negative bacterial strains. The endotoxin (lipopolysaccharide, LPS) and/or associated peptidoglycans from the bacteria are the key agents to induce an immune response, which then produces a cascade of immunological consequences. However, there are direct actions of LPS and associated peptidoglycans on cells which are commonly overlooked. This study showed behavioral and neural changes in larval Drosophila fed commercially obtained LPS from Serratia marcescens. Locomotor behavior was not altered, but feeding behavior increased and responses to sensory tactile stimuli were decreased. In driving a sensory-central nervous system (CNS)-motor neural circuit in in-situ preparations, direct application of commercially obtained LPS initially increased evoked activity and then decreased and even stopped evoked responses in a dose-dependent manner. With acute LPS and associated peptidoglycans exposure (10 min), the depressed neural responses recovered within a few minutes after removal of LPS. Commercially obtained LPS induces a transitory hyperpolarization of the body wall muscles within seconds of exposure and alters activity within the CNS circuit. Thus, LPS and/or associated peptidoglycans have direct effects on body wall muscle without a secondary immune response.

Listening to your gut: immune challenge to the gut sensitizes body wall nociception in the caterpillarManduca sexta

“…How an immune challenge in the gut decreases the threshold for nocifensive behaviour is not known. However, consumption of bacterial lipopolysaccharide (LPS) by D. melanogaster larvae also leads to a change in responsiveness to mechanosensory stimuli [56]. Larvae show a decreased responsiveness to light touch; nociceptive responses were not tested [56].…”

“…However, consumption of bacterial lipopolysaccharide (LPS) by D. melanogaster larvae also leads to a change in responsiveness to mechanosensory stimuli [56]. Larvae show a decreased responsiveness to light touch; nociceptive responses were not tested [56]. These results also suggest that there is a connection between pathogens in the gut and peripheral sensory neurons, or other neurons in the nociceptive neural circuit.…”

“…within the CNS) in D. melanogaster, leading to changes in behaviour [59]. LPS in Drosophila also has complex, concentration-dependent [58] effects on neuromuscular phenomena [56]. Therefore, peripheral sensory neurons, central neurons involved in nociception and neuromuscular connections can be altered by the presence of pathogen components in the haemocoel, leading to changes in behaviour.…”

The Effect of Bacterial Endotoxin LPS on Serotonergic Modulation of Glutamatergic Synaptic Transmission

“…LPS exposure was obtained by exchanging the untainted saline with LPS containing saline while maintaining intracellular recording. The high concentration of LPS was also used to compare with previous studies using the muscles of frog and crayfish and the CNS of rodents [ 5 , 40 ]. The LD50 in rodents for LPS from S. marcescens is 650 µg/mL (6 × 10 6 CFU-colony-forming units [ 41 ]).…”

Prolonged Transcriptional Consequences in Survivors of Sepsis

“…Drosophila species have been a pivotal model for several essential research findings, including the discovery of toll-like receptors [ 19 , 20 ]. Sepsis can be induced in Drosophila using lipopolysaccharide exposure or bacterial inoculation, providing critical information about the pathogen interacting with the host [ 21 , 22 , 23 , 24 , 25 ]. Therefore, sepsis in fruit flies is defined by most researchers as the exposure itself to a sepsis trigger, not by physiological parameters as seen in clinical settings [ 6 ].…”