Manipulative neuroparasites: uncovering the intricacies of neurological host control.

Manipulative neuroparasites are a fascinating group of organisms that possess the ability to hijack the nervous systems of their hosts, manipulating their behavior in order to enhance their own survival and reproductive success. This review provides an overview of the different strategies employed by manipulative neuroparasites, ranging from viruses to parasitic worms and fungi. By examining specific examples, such as Toxoplasma gondii, Leucochloridium paradoxum, and Ophiocordyceps unilateralis, we highlight the complex mechanisms employed by these parasites to manipulate their hosts' behavior. We explore the mechanisms through which these parasites alter the neural processes and behavior of their hosts, including the modulation of neurotransmitters, hormonal pathways, and neural circuits. This review focuses less on the diseases that neuroparasites induce and more on the process of their neurological manipulation. We also investigate the fundamental mechanisms of host manipulation in the developing field of neuroparasitology, which blends neuroscience and parasitology. Finally, understanding the complex interaction between manipulative neuroparasites and their hosts may help us to better understand the fundamentals of behavior, neurology, and host-parasite relationships.

Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling.

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacterium Pseudomonas aeruginosa induces histone H4 Lys8 acetylation (H4K8ac) in the germline of Caenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior.

The Role of the Gut Microbiota in the Prevention and Management of Gestational Diabetes Mellitus: Are We There Yet?

Current nonpharmacological approaches, including diet and exercise interventions, for preventing and treating gestational diabetes mellitus are effective for less than 50% of women. Recent evidence suggests that the gut microbiome is integrally involved in maternal glucose homeostasis. Changes to the composition and metabolic behavior of the gut microbiota may play a role in the development and persistence of gestational diabetes mellitus. Thus, there is growing interest in targeting the maternal gut microbiome for preventing and managing pregnancy-related diseases including gestational diabetes mellitus. Future progress may come from a systems biology approach to elucidate the role of the gut microbiota in maternal glucose homeostasis.

The role of microbiota in tissue repair and regeneration.

A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ-free, and the human body as the host of the biomaterials is not germ-free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.

Painful interactions: Microbial compounds and visceral pain.

Visceral pain, characterized by abdominal discomfort, originates from organs in the abdominal cavity and is a characteristic symptom in patients suffering from irritable bowel syndrome, vulvodynia or interstitial cystitis. Most organs in which visceral pain originates are in contact with the external milieu and continuously exposed to microbes. In order to maintain homeostasis and prevent infections, the immune- and nervous system in these organs cooperate to sense and eliminate (harmful) microbes. Recognition of microbial components or products by receptors expressed on cells from the immune and nervous system can activate immune responses but may also cause pain. We review the microbial compounds and their receptors that could be involved in visceral pain development.

Molecular Interactions During Borrelia burgdorferi Migration from the Vector to the Mammalian Nervous System.

Lyme disease (LD) is an infectious disease caused by the spirochetes of genus borrelia, which are transmitted by the ticks of the genus ixodes. LD is transmitted by the spirochete B. burgdorferi sensu lato. Once in contact with the host through a tick bite, the pathogen comes into contact with the host defense, and must escape this machinery to establish LD, thus using a large number of mechanisms involving the vector of the pathogen, the pathogen itself and also the host. The initial diagnosis of the disease can be made based on the clinical symptoms of LD and the disease can be treated and cured with antibiotics if the diagnosis is made early in the beginning of the disease. Contrariwise, if LD is left untreated, the pathogen disseminates throughout the tissues and organs of the body, where it establishes different types of disease manifestations. In the nervous system, the inflammation caused by B. burgdorferi is known as Lyme neuroborreliosis (LNB). LNB is one of the principal manifestations of LD. In this review, we systematically describe the different molecular interactions among B. burgdorferi, the vector (tick) and the mammalian host.

Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity.

Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. Here we conduct RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases are compared with healthy controls in whole blood and with non-TB cerebral infection controls in CSF. Whole blood RNA-Seq analysis demonstrates a distinct immune response pattern in TBM, with significant increase in both canonical and non-canonical inflammasome activation and decrease in T-cell activation. In ventricular CSF, a significant enrichment associated with neuronal excitotoxicity and cerebral damage is detected in TBM. Finally, compartmental comparison in TBM indicates that the ventricular profile represents brain injury whereas the lumbar profile represents protein translation and cytokine signaling. Together, transcriptomic analysis shows that disease processes differ between the periphery and the central nervous system, and within brain compartments.

Microbes and the Mind: How Bacteria Shape Affect, Neurological Processes, Cognition, Social Relationships, Development, and Pathology.

Recent data suggest that the human body is not so exclusively human after all. Specifically, humans share their bodies with approximately 10 trillion microorganisms, collectively known as the microbiome. Chief among these microbes are bacteria, and there is a growing consensus that they are critical to virtually all facets of normative functioning. This article reviews the ways in which bacteria shape affect, neurological processes, cognition, social relationships, development, and psychological pathology. To date, the vast majority of research on interactions between microbes and humans has been conducted by scientists outside the field of psychology, despite the fact that psychological scientists are experts in many of the topics being explored. This review aims to orient psychological scientists to the most relevant research and perspectives regarding the microbiome so that we might contribute to the now widespread, interdisciplinary effort to understand the relationship between microbes and the mind.

Perinatal Interactions between the Microbiome, Immunity, and Neurodevelopment.

The microbiome modulates host immune function across the gastrointestinal tract, peripheral lymphoid organs, and central nervous system. In this review, we highlight emerging evidence that microbial effects on select immune phenotypes arise developmentally, where the maternal and neonatal microbiome influence immune cell ontogeny in the offspring during gestation and early postnatal life. We further discuss roles for the perinatal microbiome and early-life immunity in regulating normal neurodevelopmental processes. In addition, we examine evidence that abnormalities in microbiota-neuroimmune interactions during early life are associated with altered risk of neurological disorders in humans. Finally, we conclude by evaluating the potential implications of microbiota-immune interventions for neurological conditions. Continued progress toward dissecting mechanistic interactions between the perinatal microbiota, immune system, and nervous system might uncover fundamental insights into how developmental interactions across physiological systems inform later-life health and disease.

Rethinking the Role of the Nervous System: Lessons From the Hydra Holobiont.

Here we evaluate our current understanding of the function of the nervous system in Hydra, a non-bilaterian animal which is among the first metazoans that contain neurons. We highlight growing evidence that the nervous system, with its rich repertoire of neuropeptides, is involved in controlling resident beneficial microbes. We also review observations that indicate that microbes affect the animal's behavior by directly interfering with neuronal receptors. These findings provide new insight into the original role of the nervous system, and suggest that it emerged to orchestrate multiple functions including host-microbiome interactions. The excitement of future research in the Hydra model now relies on uncovering the common rules and principles that govern the interaction between neurons and microbes and the extent to which such laws might apply to other and more complex organisms.

Common and unique strategies of male killing evolved in two distinct Drosophila symbionts.

Male killing is a selfish reproductive manipulation caused by symbiotic bacteria, where male offspring of infected hosts are selectively killed. The underlying mechanisms and the process of their evolution are of great interest not only in terms of fundamental biology, but also their potential applications. The two bacterial Drosophila symbionts, Wolbachia and Spiroplasma, have independently evolved male-killing ability. This raises the question whether the underlying mechanisms share some similarities or are specific to each bacterial species. Here, we analyse pathogenic phenotypes of D. bifasciata infected with its natural male-killing Wolbachia strain and compare them with those of D. melanogaster infected with male-killing Spiroplasma We show that male progeny infected with the Wolbachia strain die during embryogenesis with abnormal apoptosis. Interestingly, male-killing Wolbachia infection induces DNA damage and segregation defects in the dosage-compensated chromosome in male embryos, which are reminiscent of the phenotypes caused by male-killing Spiroplasma in D. melanogaster By contrast, host neural development seems to proceed normally unlike male-killing Spiroplasma infection. Our results demonstrate that the dosage-compensated chromosome is a common target of two distinct male killers, yet Spiroplasma uniquely evolved the ability to damage neural tissue of male embryos.

A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the Design and Application of Glycopeptidolipid Mutants.

Little is known about the disease-causing genetic determinants that are used by Mycobacterium abscessus, increasingly acknowledged as an important emerging pathogen, notably in cystic fibrosis. The presence or absence of surface exposed glycopeptidolipids (GPL) conditions the smooth (S) or rough (R) M. abscessus subsp. abscessus (M. abscessus) variants, respectively, which are characterized by distinct infective programs. However, only a handful of successful gene knock-out and conditional mutants have been reported in M. abscessus, testifying that genetic manipulation of this mycobacterium is difficult. To facilitate gene disruption and generation of conditional mutants in M. abscessus, we have designed a one-step single cross-over system that allows the rapid and simple generation of such mutants. Cloning of as small as 300 bp of the target gene allows for efficient homologous recombination to occur without additional exogenous recombination-promoting factors. The presence of tdTomato on the plasmids allows easily sifting out the large background of mutants spontaneously resistant to antibiotics. Using this strategy in the S genetic background and the target gene mmpL4a, necessary for GPL synthesis and transport, nearly 100% of red fluorescent clones exhibited a rough morphotype and lost GPL on the surface, suggesting that most red fluorescent colonies obtained after transformation incorporated the plasmid through homologous recombination into the chromosome. This system was further exploited to generate another strain with reduced GPL levels to explore how the presence of these cell wall-associated glycolipids influences M. abscessus hydrophobicity as well as virulence in the zebrafish model of infection. This mutant exhibited a more pronounced killing phenotype in zebrafish embryos compared to its S progenitor and this effect correlated with the production of abscesses in the central nervous system. Overall, these results suggest that the near-complete absence of GPL on the bacterial surface is a necessary condition for optimal pathogenesis of this mycobacterium. They also suggest that GPL content affects hydrophobicity of M. abscessus, potentially altering the aerosol transmission, which is of particular importance from an epidemiological and clinical perspective.

Role of Neurochemicals in the Interaction between the Microbiota and the Immune and the Nervous System of the Host Organism.

This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium-immune system-nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical "language." It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota-host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/neurohormones because they have adapted to them during the course of many millions of years of microbiota-host coevolution. We emphasize that the terms "microbiota" and "microbial consortium" are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium-immune system-nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target-oriented probiotic preparations produce important side effects on a wide variety of processes in the host organism. In particular, we should take into account probiotics' capacity to produce mediators that can considerably modify the operation of the microecological, immune, and nervous system of the human organism.

The ability of lipopolysaccharide (LPS) of Pasteurella multocida B:2 to induce clinical and pathological lesions in the nervous system of buffalo calves following experimental inoculation.

Lipopolysaccharide (LPS) of P. multocida B:2, a causative agent of haemorrhagic septicaemia (HS) in cattle and buffaloes, is considered as the main virulence factor and contribute in the pathogenesis of the disease. Recent studies provided evidences about the involvement of the nervous system in pathogenesis of HS. However, the role of P. multocida B:2 immunogens, especially the LPS is still uncovered. Therefore, this study was designed to investigate the role of P. multocida B:2 LPS to induce pathological changes in the nervous system. Nine eight-month-old, clinically healthy buffalo calves were used and distributed into three groups. Calves of Group 1 and 2 were inoculated orally and intravenously with 10 ml of LPS broth extract represent 1 × 1012 cfu/ml of P. multocida B:2, respectively, while calves of Group 3 were inoculated orally with 10 ml of phosphate buffer saline as a control. Significant differences were found in the mean scores for clinical signs, post mortem and histopathological changes especially in Group 2, which mainly affect different anatomic regions of the nervous system, mainly the brain. On the other hand, lower scores have been recorded for clinical signs, gross and histopathological changes in Group 1. These results provide for the first time strong evidence about the ability of P. multocida B:2 LPS to cross the blood brain barrier and induce pathological changes in the nervous system of the affected buffalo calves.

Neuroborreliosis.

Appropriate, critical application of evidence-based diagnostic criteria enables both a clear definition of what constitutes neuroborreliosis-nervous system infection with Borrelia burgdorferi sensu stricto in the US, B garinii and less commonly B. afzelii and other species in Europe-and recognition that this disorder is quite similar in Europe and the US. Most commonly evidenced by lymphocytic meningitis and/or multifocal inflammation of the peripheral (common; cranial neuropathy, radiculopathy, mononeuropathy multiplex) or central (rare) nervous system, it is readily diagnosed and highly antibiotic responsive. Encephalopathy-altered cognition or memory-can occur as part of the systemic infection and inflammatory state, but is not evidence of neuroborreliosis. Post treatment Lyme disease syndrome-persistent neurobehavioral symptoms 6 months or more after usually curative antibiotic treatment-if real and not simply an example of anchoring bias-is unrelated to neuroborreliosis. The pathophysiology of neuroborreliosis remains unclear, but appears to involve both a requirement for viable micro-organisms and significant immune amplification.

Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis.

The concept of a gut microbiota-brain axis has emerged to describe the complex and continuous signalling between the gut microbiota and host nervous system. This review examines key microbial-derived neuromodulators and structural components that comprise the gut microbiota-brain axis. To conclude, we briefly identify current challenges in gut microbiota-brain research and suggest a framework to characterize these interactions. Here, we propose five emerging hallmarks of the gut microbiota-brain axis: (i) Indistinguishability, (ii) Emergence, (iii) Bidirectional Signalling, (iv) Critical Window Fluidity and (5) Neural Homeostasis.

Absceso cerebral en pacientes pediatricos / Brain abscess in pediatric patients

El absceso cerebral se constituye como un área central supurativa dentro del parénquima cerebral, dentro de una envoltura ampliamente vascularizada. Los patógenos ampliamente aislados en la patogénesis de esta entidad en niños son los Streptococos spp. A pesar del avance en la terapia antimicrobiana, las técnicas neuroquirúrgicas e imagenológicas, que permiten su diagnóstico y ubicación oportuna, el absceso cerebral aún se considera un problema de salud pública, con una importante incidencia, morbilidad y mortalidad en países en vía de desarrollo. Para el manejo de este tipo de infección del SNC, se requerirá de un abordaje multidisciplinario que involucre terapia médico quirúrgica. El objetivo de esta revisión es hacer un abordaje amplio sobre la patobiología del absceso cerebral relacionada con la labor concerniente al neurocirujano.

Brain abscess is formed as a central suppurativa area within the brain parenchyma, within an envelope extensively vascularized. Microorganisms largely isolated in the pathogenesis of this condition in children are Streptococos spp. Despite the progress in antimicrobial therapy, neurosurgical techniques and imagenologic support, which enabling timely diagnosis and location, brain abscess is still considered a public health problem and has an important incidence, morbidity and mortality in developing countries. To handle this type of CNS infection, will require a multidisciplinary approach involving surgical medical therapy. The aim of this review is to make a comprehensive approach on the pathobiology of brain abscess related to the work concerning the neurosurgeon.

Interactions of neuropathogenic Escherichia coli K1 (RS218) and its derivatives lacking genomic islands with phagocytic Acanthamoeba castellanii and nonphagocytic brain endothelial cells.

Here we determined the role of various genomic islands in E. coli K1 interactions with phagocytic A. castellanii and nonphagocytic brain microvascular endothelial cells. The findings revealed that the genomic islands deletion mutants of RS218 related to toxins (peptide toxin, α -hemolysin), adhesins (P fimbriae, F17-like fimbriae, nonfimbrial adhesins, Hek, and hemagglutinin), protein secretion system (T1SS for hemolysin), invasins (IbeA, CNF1), metabolism (D-serine catabolism, dihydroxyacetone, glycerol, and glyoxylate metabolism) showed reduced interactions with both A. castellanii and brain microvascular endothelial cells. Interestingly, the deletion of RS218-derived genomic island 21 containing adhesins (P fimbriae, F17-like fimbriae, nonfimbrial adhesins, Hek, and hemagglutinin), protein secretion system (T1SS for hemolysin), invasins (CNF1), metabolism (D-serine catabolism) abolished E. coli K1-mediated HBMEC cytotoxicity in a CNF1-independent manner. Therefore, the characterization of these genomic islands should reveal mechanisms of evolutionary gain for E. coli K1 pathogenicity.

Mechanisms of staphylococcal enterotoxin-induced emesis.

Pathogenic bacteria use various strategies to interact with the host organisms. Among them, toxin production constitutes an efficient way to alter specific functions of target cells. Various enterotoxins interact with the enteric nervous system, by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, diarrhea, or in the intestinal inflammation process. Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs) with demonstrated emetic activity; and staphylococcal enterotoxin-like (SEl) proteins, which are not emetic in a primate model or have yet to be tested. SEs and SEls have been traditionally subdivided into classical (SEA to SEE) and new (SEG to SElX) types. These toxins possess superantigenic activity and are highly resistant to denaturation which allows them to remain intact in contaminated foods and trigger food poisoning outbreaks. Symptoms are of rapid onset, and include nausea and violent vomiting. SEA is the most recognizable toxin causing food poisoning in humans throughout the world. However, it remains unclear how SEs induce emesis and via which signal pathway. This review is divided into four parts, and will focus on the following: (1) how bacterial toxins interact with the nervous system, (2) biological characteristics of SEs and SEls, (3) mechanisms of SE-induced emesis, and (4) use of a vaccine for the prevention of SE-induced emesis.