Evolutionary biology and the treatment of signs and symptoms of infectious disease.
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Animals↗
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Results for “Host Microbial Interactions”
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Microbial-gut interactions in health and disease. Epithelial cell responses.
Pathogenic bacteria use many strategies to secure their survival within the host. Enteropathogens exploit intestinal epithelial cells in many ways, including the manipulation of normal cellular functioning, or of cellular structural components, or by the induction of signalling pathways, such as the production of pro-inflammatory cytokines. However, the enterocyte warns the host of impending danger and, in turn, elicits a protective response. Pathogens are detected by epithelial cells owing to their vast array of surface antigens and secreted products. Epithelial cells have developed both extracellular and intracellular sensing proteins that function as a first line of defence against pathogens; this is followed by acquired immunity, namely IgA, which is used as reinforcement. Thus, in a game of constant attack and defence, the pathogen and the enterocyte aim to outsmart each other in an effort to survive.
Enterobacteriaceae↗
Prevention of urinary tract infection.
Recurrent UTI remains an exceedingly common clinical problem among women of all ages. Among otherwise healthy premenopausal and postmenopausal women, increased susceptibility to recurrences seems to be conferred by intrinsic host factors, such as nonsecretor genotype or estrogen status, and by exogenous exposures or behaviors, such as use of a diaphragm with spermicide, antimicrobial use, and sexual behavior. The natural history of recurrent UTIs is notable for a temporal clustering phenomenon, the tendency of women to revert to a baseline infection pattern after the cessation of preventive interventions, and repeated serial reinfections of the urinary tract from the fecal reservoir, often by genetically identical organisms. Low-dose antimicrobial regimens given daily, three times weekly, or postcoitally are effective in preventing recurrences in most women with a predisposition to frequent infection. Intermittent patient-initiated self-treatment is an appropriate and effective option in some patients with lower recurrence rates. In postmenopausal women, estrogen replacement therapy, particularly vaginally applied estriol creams, may also significantly reduce the rate of recurrent UTI. Ongoing investigations in the areas of microbial ecology of the vaginal flora, the molecular basis for host-parasite interactions within the urinary tract, and vaccine development may eventually lead to improved means to prevent recurrent urinary tract infections more effectively.
Adult↗
Rv2741 Promotes Mycobacterium Survival by Modulating Macrophage Function via the IL-1α-MAPK Axis.
One of the primary healthcare problems in the world today is tuberculosis (TB), a chronic infectious illness brought on by Mycobacterium tuberculosis (M. tuberculosis). A distinct family of PE_PGRS proteins, encoded by the M. tuberculosis genome, has attracted more attention because of their involvement in immune evasion and bacterial pathogenicity. Nevertheless, the specific functions and mechanisms of action for the majority of PE_PGRS proteins remain largely unexplored. This study focuses on the Rv2741 (PE_PGRS47) gene, which is exclusively present in pathogenic mycobacteria. To examine the function of Rv2741 in host-pathogen interactions, we created recombinant strains of Mycobacterium smegmatis (M. smegmatis) that expressed the M. tuberculosis Rv2741 gene. IL-1α was found to be a key mediator of host response modulation by Rv2741. Rv2741 downregulates the secretion of IL-1α and inhibits the MAPK signaling pathway, particularly the p38 and ERK1/2 pathways, thereby cooperatively inhibiting macrophage autophagy and apoptosis. Meanwhile, the decrease in IL-1α secretion directly leads to changes in the cytokine secretion pattern and a reduction in nitric oxide (NO) production. This multifaceted regulatory mechanism ultimately favors the survival of M. smegmatis in macrophages. This research significantly expands our understanding of Rv2741 function, revealing its crucial role as a multifunctional virulence factor in the immune evasion of M. tuberculosis.
Interleukin-1alpha↗
Legionella pneumophila glucosyltransferase inhibits host elongation factor 1A.
Legionella pneumophila, the causal agent of Legionnaires' disease, is an intracellular parasite and invades and proliferates within different eukaryotic cells, including human alveolar macrophages. After several 100-fold multiplication within host cells, the pathogens are released for new invasion by induction of apoptosis or necrosis. Here we report that L. pneumophila produces a glucosyltransferase, which selectively modifies an approximately 50-kDa mammalian protein by using UDP-glucose as a cosubstrate. MS analysis identified the protein substrate as the mammalian elongation factor (EF)1A. Legionella glucosyltransferase modifies its eukaryotic protein substrate at serine-53, which is located in the GTPase domain of the EF. Glucosylation of EF1A results in inhibition of eukaryotic protein synthesis and death of target cells. Our findings show a mode of inhibition of protein synthesis by microbial pathogens and offer a perspective for understanding of the host-pathogen interaction of L. pneumophila.
Amino Acid Sequence↗
Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells.
The activated macrophage may play a central role in host effector mechanisms against invading fungi. Here we demonstrate the importance of the activation state of murine macrophages for both fungistatic and fungicidal activity. Host factors such as gamma interferon and microbial products such as endotoxin can interact synergistically to initiate this cytotoxicity. This activated state may be aided by antifungal agents such as amphotericin B. Both a methyl ester derivative of amphotericin B and liposomal amphotericin B Both a methyl ester derivative of amphotericin B and liposomal amphotericin B potentiated macrophage activation but were less potent than amphotericin B. Other available antifungal agents such as azole compounds and flucytosine did not possess this ability to interact with the intrinsic macrophage effector mechanisms. However, ketoconazole and itraconazole avidly bind to macrophages as the biologically active drug. The azole-loading of macrophages may be a factor in macrophage cytotoxicity for fungi.
Animals↗
Periodontal therapeutics--a viable option?
Research in recent years in periodontology has seen a shift from surgery towards medicine. While surgery, particularly regenerative, and including implants, continues to form an important element of periodontal treatment, the volume of treatment required and the results of recent and ongoing non-surgical studies clearly show that most future periodontics will be based on a physician-type approach. Improved diagnostics based on more precise periodontal disease classification, simplification of mechanical oral hygiene equipment and procedures, and the development of conventional and non-conventional chemical and physical adjuncts may be expected to reduce the rate of common periodontal disease advance, resulting in less complex treatments, and more of the latter coming to lie within the competence of the generalist and the hygienist working together. The rationale for non-surgical adjunctive therapy is extensive, far beyond the usual antimicrobial logic. It will also be important to control the oral microflora for systemic reasons, since increasingly strong links are being established between focal infection of oral origin, much of it periodontal, and a range of systemic diseases, including coronary heart disease, stroke, gastrointestinal disorders, and low birth weight, apart from severe, overt systemic infections. All these developments derive from a greatly improved understanding of the fundamentally ecological nature of the natural microbial biofilm that is dental plaque, and of its interactions with its human host.
Anti-Bacterial Agents↗
Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis.
Streptococcus suis serotype 2 is a porcine and human pathogen with adhesive and invasive properties. In other streptococci, large surface-associated proteins (>100 kDa) of the MSCRAMM family (microbial surface components recognizing adhesive matrix molecules) are key players in interactions with host tissue. In this study, we identified a novel opacity factor of S. suis (OFS) with structural homology to members of the MSCRAMM family. The N-terminal region of OFS is homologous to the respective regions of fibronectin-binding protein A (FnBA) of Streptococcus dysgalactiae and the serum opacity factor (SOF) of Streptococcus pyogenes. Similar to these two proteins, the N-terminal domain of OFS opacified horse serum. Serum opacification activity was detectable in sodium dodecyl sulfate extracts of wild-type S. suis but not in extracts of isogenic ofs knockout mutants. Heterologous expression of OFS in Lactococcus lactis demonstrated that a high level of expression of OFS is sufficient to provide surface-associated serum opacification activity. Furthermore, serum opacification could be inhibited by an antiserum against recombinant OFS. The C-terminal repetitive sequence elements of OFS differed significantly from the respective repeat regions of FnBA and SOF as well as from the consensus sequence of the fibronectin-binding repeats of MSCRAMMs. Accordingly, fibronectin binding was not detectable in recombinant OFS. To investigate the putative function of OFS in the pathogenesis of invasive S. suis diseases, piglets were experimentally infected with an isogenic mutant strain in which the ofs gene had been knocked out by an in-frame deletion. The mutant was severely attenuated in virulence but not in colonization, demonstrating that OFS represents a novel virulence determinant of S. suis.
Amino Acid Sequence↗
Viruses' life history: towards a mechanistic basis of a trade-off between survival and reproduction among phages.
Life history theory accounts for variations in many traits involved in the reproduction and survival of living organisms, by determining the constraints leading to trade-offs among these different traits. The main life history traits of phages-viruses that infect bacteria-are the multiplication rate in the host, the survivorship of virions in the external environment, and their mode of transmission. By comparing life history traits of 16 phages infecting the bacteria Escherichia coli, we show that their mortality rate is constant with time and positively [corrected] correlated to their multiplication rate in the bacterial host. Even though these viruses do not age, this result is in line with the trade-off between survival and reproduction previously observed in numerous aging organisms. Furthermore, a multiple regression shows that the combined effects of two physical parameters, namely, the capsid thickness and the density of the packaged genome, account for 82% of the variation in the mortality rate. The correlations between life history traits and physical characteristics of virions may provide a mechanistic explanation of this trade-off. The fact that this trade-off is present in this very simple biological situation suggests that it might be a fundamental property of evolving entities produced under constraints. Moreover, such a positive correlation between mortality and multiplication reveals an underexplored trade-off in host-parasite interactions.
Bacteriophages↗
Regulation of Wolbachia density in the Mediterranean flour moth, Ephestia kuehniella, and the almond moth, Cadra cautella.
The Mediterranean flour moth, Ephestia kuehniella, is infected with A-group Wolbachia (wKue), and the almond moth, Cadra cautella, is doubly infected with A- and B-group Wolbachia, which are designated as wCauA and wCauB, respectively. In both insects, the Wolbachia populations increased greatly during embryonic and larval stages. The Wolbachia population doubled every 3.6 days on average in E. kuehniella larvae, whereas those of wCauA and wCauB doubled every 2.1 days in C. cautella larvae. The populations of wCauA and wCauB that had been transferred into the E. kuehniella background increased at similar rates to that of wKue in the natural host E. kuehniella, suggesting that the host genetic background influences Wolbachia proliferation. To examine whether the populations of the two Wolbachia variants in double infection is regulated collectively or independently, we measured the infection load in the ovaries of three transfected E. kuehniella lines in different infection states: single infection with wCauA, single infection with wCauB, and double infection. The density of each Wolbachia variant did not differ significantly between the singly and doubly transfected hosts, suggesting independent regulation.
Animals↗
Probiotic research in Australia, New Zealand and the Asia-Pacific region.
Although the epicentres of probiotic research in the past decade have been Japan and Europe, researchers in the Asia-Pacific region have actively contributed to the growing understanding of the intestinal microbial ecosystem, and interactions between gut bacteria, diet and health of the human host. A number of new probiotic strains have been developed in the region that have been demonstrated to have beneficial impacts on health in animal and human trials, including improved protection against intestinal pathogens and modulation of the immune system. Probiotics targeted to animals, including aquaculture, feature heavily in many Asian countries. Developments in probiotic technologies have included microencapsulation techniques, antimicrobial production in fermented meats, and synbiotic combinations. In particular, the impact of resistant starch on the intestinal environment and fermentation by intestinal bacteria has been intensively studied and new probiotic strains selected specifically for synbiotic combinations with resistant starch. This paper provides an overview of probiotic research within Australia, New Zealand and a number of Asian countries, and lists scientists in the Asia-Pacific region involved in various aspects of probiotic research and development.
Academies and Institutes↗
[Nutrition in the etiopathogenesis of chronic inflammatory bowel diseases].
It is currently held that the pathogenesis of inflammatory bowel disease (IBD) involves a complex interaction of host responses, some immunologic and genetically determined, and external influences including microbial and dietary factors. Nutritional surveys and studies testing stepwise exclusion dietary compounds have suggested that dietary factors might be linked to the occurrence of IBD. Food allergy was suggested early as a possible trigger for the inflammatory response; however, no firm evidence has been gathered over the years to substantiate this possibility. The possibility that patients with Crohn's disease may have an unusual premorbid pattern of dietary intake has also been examined since the early seventies. Several groups of investigators report a high intake of refined sugars (i.e. sucrose), recycled cooking oil, a more frequent consumption of fast foods in patients with Crohn's disease and ulcerative colitis respectively. However, a critical comparison of incidence and prevalence studies published from 1976 until 1994 clearly showed no pre-existing nutritional abnormality that has been identified consistently in patients who develop inflammatory bowel disease.
Adolescent↗
Immunology, microbiology, and the recalcitrant wound.
Wounding of normal skin initiates an acute inflammatory response that ordinarily contributes to the healing process. The underlying process is orchestrated by the specific and nonspecific immune response. Inflammatory cells provide growth factors and stimulate the deposition of matrix proteins and phagocytose debris. However, the maturation and resolution of a wound may be complicated by micro-organisms. The effects of micro-organisms on oxygen consumption and pH, or toxin production, may interrupt the natural course of wound healing. Thus, a wound may not progress from the acute phase and heal, but may become a nonhealing chronic or recalcitrant wound as long as the antigens from micro-organisms or underlying pathology remain. Depending on the underlying disease pathology and the micro-organism's virulence, microbial growth in acute or chronic wounds may lead to invasive wound infection. Wound infection is a complex interaction involving the host as well as the numbers and types of micro-organisms present. The literature suggests that micro-organisms alter the course of acute wound healing, and a body of evidence exists that suggests that large numbers of organisms in chronic wounds delay the healing process. However, other evidence suggests that, despite bacteria, most chronic wounds progress toward healing, depending upon the wound care strategy employed. Current therapy seeks to alter the relationships between microbial colonization and host defenses by providing an environment that tips the balance in favor of healing. The role of bacteria in acute and chronic wounds may span the spectrum from initiation of inflammation and the healing process, to colonization, invasive infection, systemic sepsis, organ system failure, and death. Understanding the interaction of the wound, wound micro-organisms, and the immune response is central to understanding how best to develop therapeutic approaches.
Chronic Disease↗
Common themes in microbial pathogenicity.
A bacterial pathogen is a highly adapted microorganism which has the capacity to cause disease. The mechanisms used by pathogenic bacteria to cause infection and disease usually include an interactive group of virulence determinants, sometimes coregulated, which are suited for the interaction of a particular microorganism with a specific host. Because pathogens must overcome similar host barriers, common themes in microbial pathogenesis have evolved. However, these mechanisms are diverse between species and not necessarily conserved; instead, convergent evolution has developed several different mechanisms to overcome host barriers. The success of a bacterial pathogen can be measured by the degree with which it replicates after entering the host and reaching its specific niche. Successful microbial infection reflects persistence within a host and avoidance or neutralization of the specific and nonspecific defense mechanisms of the host. The degree of success of a pathogen is dependent upon the status of the host. As pathogens pass through a host, they are exposed to new environments. Highly adapted pathogenic organisms have developed biochemical sensors exquisitely designed to measure and respond to such environmental stimuli and accordingly to regulate a cascade of virulence determinants essential for life within the host. The pathogenic state is the product of dynamic selective pressures on microbial populations.
Animals↗
Host defense peptides and lipopeptides: modes of action and potential candidates for the treatment of bacterial and fungal infections.
Endogenous peptide antibiotics (termed also host-defense or antimicrobial peptides) are known as evolutionarily old components of innate immunity. They were found initially in invertebrates, but later on also in vertebrates, including humans. This secondary, chemical immune system provides organisms with a repertoire of small peptides that act against invasion (for both offensive and defensive purposes) by occasional and obligate pathogens. Each antimicrobial peptide has a broad but not identical spectrum of antimicrobial activity, predominantly against bacteria, providing the host maximum coverage against a rather broad spectrum of microbial organisms. Many of these peptides interact with the target cell membranes and increase their permeability, which results in cell lysis. A second important family includes lipopeptides. They are produced in bacteria and fungi during cultivation on various carbon sources, and possess a strong antifungal activity. Unfortunately, native lipopeptides are non-cell selective and therefore extremely toxic to mammalian cells. Whereas extensive studies have emerged on the requirements for a peptide to be antibacterial, very little is known concerning the parameters that contribute to antifungal activity. This review summarizes recent studies aimed to understand how antimicrobial peptides and lipopeptides select their target cell. This includes a new group of lipopeptides highly potent against pathogenic fungi and yeast. They are composed of inert cationic peptides conjugated to aliphatic acids with different lengths. Deep understanding of the molecular mechanisms underlying the differential cells specificity of these families of host defense molecule is required to meet the challenges imposed by the life-threatening infections.
Bacterial Infections↗
Selected animal models: vaginal candidosis, Pneumocystis pneumonia, dermatophytosis and trichosporosis.
A clear understanding of the pathogenesis of fungal disease remains elusive. While technological advances in molecular biology and microbial genetics have provided scientists with major new insights into both microbial virulence factors as well as host susceptibility to infection, there is currently no substitute for animal models in elucidating microbe-host interactions. Animal models are also essential for the evaluation of new antimicrobial agents, including studies of efficacy, adverse reactions and pharmacokinetics. The single most important advance in animal models in the last decade, has been the availability of genetically unique strains of animals as alternative to animals treated with immunosuppressive drugs for use in studies on microbial virulence and host defence mechanisms. These unique strains of test animals also enhance our understanding of the modes of action of antifungal drugs and their metabolism. Some of these advances will be discussed in this symposium.
Animals↗
Microbial dynamics and interactions in the spermosphere.
The spermosphere represents a short-lived, rapidly changing, and microbiologically dynamic zone of soil surrounding a germinating seed. It is analogous to the rhizosphere, being established largely by the carbon compounds released into the soil once the seed begins to hydrate. These seed exudations drive the microbial activities that take place in the spermosphere, many of which can have long-lasting impacts on plant growth and development as well as on plant health. In this review, I discuss the nature of the spermosphere habitat and the factors that give rise to its character, with emphasis on the types of microbial activities in the spermosphere that have important implications for disease development and biological disease control. This review, which represents the first comprehensive synthesis of the literature on spermosphere biology, is meant to illustrate the unique nature of the spermosphere and how studies of interactions in this habitat may serve as useful experimental models for testing hypotheses about plant-microbe associations and microbial ecology.
Animals↗
Parallel single-cell host immune profiling and pathogen genomic characterization in Klebsiella-associated sepsis: a pilot study.
OBJECTIVES: Sepsis is a life-threatening syndrome characterized by profound immune dysregulation and substantial biological heterogeneity. Here, we conducted a pilot study to explore host immune remodeling in Klebsiella-associated sepsis by combining single-cell RNA sequencing of peripheral blood mononuclear cells with whole-genome sequencing of the corresponding bloodstream isolates. METHODS: In this prospective observational pilot study, we analyzed peripheral blood mononuclear cells (PBMCs) from two patients with Klebsiella-associated sepsis and two healthy controls (HC) using single-cell RNA sequencing. PBMC composition, differential transcriptional responses, and pathway analysis were assessed across immune subsets. The corresponding bloodstream isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing. RESULTS: Compared to HC, septic patients showed expansion of the myeloid compartment and contraction of the NK/T compartment. High-resolution analysis suggested shifts within lymphoid populations. At the transcriptional level, sepsis was associated with compartment-specific enrichment of interferon-related and host-defence pathways, as well as oxidative phosphorylation, ATP synthesis, and mitochondrial electron transport signatures across multiple PBMC subsets. Classical monocytes exhibited a coordinated decrease in MHC class II-related transcripts. The sepsis-associated isolates were identified as Klebsiella pneumoniae and Klebsiella variicola and were notable for overall antimicrobial susceptibility, limited resistomes, and absence of canonical hypervirulence determinants. CONCLUSION: Our data provide a preliminary description of immune remodeling during Klebsiella-associated sepsis and suggest that severe clinical disease may be associated with isolates lacking classical multidrug-resistance or hypervirulence features. These findings should be interpreted as preliminary and hypothesis-generating and require validation in larger cohorts with detailed clinical severity assessment.
Female↗