Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Certain Query Answering on Compressed String Patterns: From Streams to Hyperstreams

International audienceWe study the problem of certain query answering (CQA) on compressed string patterns. These are incomplete singleton context-free grammars, that can model systems of multiple streams with references to others, called hyperstreams more recently. In order to capture regular path queries on strings, we consider nondeterministic finite automata (NFAs) for query definition. It turns out that CQA for Boolean NFA queries is equivalent to regular string pattern inclusion, i.e., whether all strings completing a compressed string pattern belong to a regular language. We prove that CQA on compressed string patterns is PSpace- complete for NFA queries. The PSpace-hardness even applies to Boolean queries defined by deterministic finite automata (DFAs) and without compression. We also show that CQA on compressed linear string patterns can be solved in PTime for DFA queries. The proofs of the results presented here can be found in the long version of this paper (https://hal.inria.fr/hal-01846016)

Nested Regular Expressions can be Compiled to Small Deterministic Nested Word Automata

International audienceWe study the problem of whether regular expressions for nested words can be compiled to small deterministic nested word au-tomata (NWAs). In theory, we obtain a positive answer for small deter-ministic regular expressions for nested words. In practice of navigational path queries, nondeterministic NWAs are obtained for which NWA de-terminization explodes. We show that practical good solutions can be obtained by using stepwise hedge automata as intermediates

ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks

An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ∼0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain

Regulation of Spike Timing-Dependent Plasticity of Olfactory Inputs in Mitral Cells in the Rat Olfactory Bulb

The recent history of activity input onto granule cells (GCs) in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON) inputs to mitral cells (MCs). Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs) with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP) was achieved by the regulation of the inter-spike-interval (ISI) of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb

Label-free smartphone quantitation of bacteria by darkfield imaging of light scattering in fluoropolymer micro capillary film allows portable detection of bacteriophage lysis

Conventional methods for the detection and quantitation of bacteria are slow, laborious and require a laboratory. Microfluidic systems offer faster and portable testing, and smartphone cameras can record colorimetric or fluorometric bioassays, but this requires dye addition. Here, we demonstrate for the first time label-free smartphone detection of bacterial light scattering by darkfield microfluidic imaging to measure bacteria and bacteriophage lysis. A single LED and portable 3D printed imaging box allowed bacterial concentration and growth to be measured by direct imaging of bacterial light scattering. Bacteriophage lysis was detected within a 10-channel microfluidic device made from melt-extruded fluoropolymer micro capillary film, allowing rapid detection of host specificity. Elimination of unwanted reflections and optimising illumination angle are critical for successful darkfield bacterial imaging, with 15° giving maximal intensity. Bacterial sedimentation was directly observed within microfluidic devices, and detection sensitivity significantly increased by allowing bacteria to sediment for 30 min. With this simple, low-cost, 3D printed system bacterial concentrations down to an optical density of 0.1 could be measured corresponding to 8 × 104 colony forming units (CFU) per microdevice, approaching the sensitivity of conventional spectrophotometers. Bacteriophage lysis could be detected at a range of starting cell concentrations. With a low starting cell concentration, the increase in light scatter signal with incubation was prevented in the presence of bacteriophage. Conversely, with high starting cell concentration, the light scatter signal detected at the start was clearly eliminated when phage were added, indicating this simple system allows direct visualisation of bacteriophage eliminating light scattering by lysis

An intrinsic vasopressin system in the olfactory bulb is involved in social recognition

Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain where they play fundamentally important roles in social behaviours1. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders, and obsessive-compulsive disorder, and polymorphisms of the vasopressin V1a receptor have been linked to autism2,3. Here we report that the rat olfactory bulb contains a large population of interneurones which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats, and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurones. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system