Seasonal changes in the environment, such as varying temperature, have the potential to change the functional relationship between ectothermic animals, such as insects, and their microbiomes. Our ...objectives were to determine: (a) whether seasonal changes in temperature shift the composition of the insect gut microbiome, and (b) whether changes in the microbiome are concomitant with changes in the physiology of the host, including the immune system and response to cold.
We exposed laboratory populations of the spring field cricket, Gryllus veletis (Orthoptera: Gryllidae), to simulated overwintering conditions in both a laboratory microcosm and a field‐like microcosm containing soil and leaves. In summer, autumn, winter and spring, we extracted and sequenced 16S bacterial genomic DNA from cricket guts, to capture seasonal variation in the composition of the microbiome.
The composition of the gut microbiome was similar between microcosms, and overall highly anaerobic. In both microcosms, we captured similar seasonal variation in the composition of the microbiome, where overwintering resulted in permanent changes to these microbial communities. In particular, the abundance of Pseudomonas spp. decreased, and that of Wolbachia spp. increased, during overwintering.
Concurrent with overwintering changes in the gut microbiome, G. veletis acquire freeze tolerance and immune function shifts temporarily, returning to summer levels of activity in the spring. In a specific manner, haemocyte concentrations increase but survival of fungal infection decreases in the winter, whereas the ability to clear bacteria from the haemolymph remains unchanged.
Overall, we demonstrate that the gut microbiome does shift seasonally, and in concert with other physiological changes. We hypothesize that these changes may be linked, and suggest that it will next be important to determine whether these changes in the microbiome contribute to host overwintering success.
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Plain Language Summary
Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative ...staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis. We identify a 6-TG biosynthetic gene cluster in S. chromogenes and other coagulase-negative staphylococci including S. epidermidis, S. pseudintermedius and S. capitis. Recombinant S. aureus strains harbouring this operon produce 6-TG and, when used in subcutaneous co-infections in mice with virulent S. aureus USA300, protect the host from necrotic lesion formation. Used prophylactically, 6-TG reduces necrotic skin lesions in mice infected with USA300, and this effect is mediated by abrogation of toxin production. RNAseq analyses reveal that 6-TG downregulates expression of genes coding for purine biosynthesis, the accessory gene regulator (agr) and ribosomal proteins in S. aureus, providing an explanation for its effect on toxin production.
Macrophages are critical to innate immunity due to their ability to phagocytose bacteria. The macrophage phagolysosome is a highly acidic organelle with potent antimicrobial properties, yet ...remarkably, ingested
replicates within this niche. Herein we demonstrate that
requires the GraXRS regulatory system for growth within this niche, while the SaeRS and AgrAC two-component regulatory systems and the α-phenol soluble modulins are dispensable. Importantly, we find that it is exposure to acidic pH that is required for optimal growth of
inside fully acidified macrophage phagolysosomes. Exposure of
to acidic pH evokes GraS signaling, which in turn elicits an adaptive response that endows the bacteria with increased resistance to antimicrobial effectors, such as antimicrobial peptides, encountered inside macrophage phagolysosomes. Notably, pH-dependent induction of antimicrobial peptide resistance in
requires the GraS sensor kinase. GraS and MprF, a member of the GraS regulon, play an important role for bacterial survival in the acute stages of systemic infection, where in murine models of infection,
resides within liver-resident Kupffer cells. We conclude that GraXRS represents a vital regulatory system that functions to allow
to evade killing, prior to commencement of replication, within host antibacterial immune cells.
can infect any site of the body, including the microbicidal phagolysosome of the macrophage. The ability of
to infect diverse niches necessitates that the bacteria be highly adaptable. Here we show that
responds to phagolysosome acidification to evoke changes in gene expression that enable the bacteria to resist phagolysosomal killing and to promote replication. Toxin production is dispensable for this response; however, the bacteria require the sensor kinase GraS, which transduces signals in response to acidic pH. GraS is necessary for phagolysosomal replication and survival of
in the acute stage of systemic infection. Disruption of this
adaptation would render
susceptible to phagocyte restriction.
Iron is an essential micronutrient for both microbes and humans alike. For well over half a century we have known that this element, in particular, plays a pivotal role in health and disease and, ...most especially, in shaping host-pathogen interactions. Intracellular iron concentrations serve as a critical signal in regulating the expression not only of high-affinity iron acquisition systems in bacteria, but also of toxins and other noted virulence factors produced by some major human pathogens. While we now are aware of many strategies that the host has devised to sequester iron from invading microbes, there are as many if not more sophisticated mechanisms by which successful pathogens overcome nutritional immunity imposed by the host. This review discusses some of the essential components of iron sequestration and scavenging mechanisms of the host, as well as representative Gram-negative and Gram-positive pathogens, and highlights recent advances in the field. Last, we address how the iron acquisition strategies of pathogenic bacteria may be exploited for the development of novel prophylactics or antimicrobials.
Abstract
Modified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase ...responsible for installing m
3
C
32
in the human mitochondrial (mt-)tRNA
Thr
and mt-tRNA
Ser(UCN)
. METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mt-tRNA recognition elements revealed U
34
G
35
and t
6
A
37
/(ms
2
)i
6
A
37
, present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C
32
. Several lines of evidence demonstrate the influence of U
34
, G
35
, and the m
3
C
32
and t
6
A
37
/(ms
2
)i
6
A
37
modifications in mt-tRNA
Thr/Ser(UCN)
on the structure of these mt-tRNAs. Although mt-tRNA
Thr/Ser(UCN)
lacking METTL8-mediated m
3
C
32
are efficiently aminoacylated and associate with mitochondrial ribosomes, mitochondrial translation is mildly impaired by lack of METTL8. Together these results define the cellular targets of METTL8 and shed new light on the role of m
3
C
32
within mt-tRNAs.
Both biosociological and psychological models, as well as animal research, suggest that testosterone has a key role in social interactions. Evidence from animal studies in rodents shows that ...testosterone causes aggressive behaviour towards conspecifics. Folk wisdom generalizes and adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic, or even aggressive human behaviours. However, many researchers have questioned this folk hypothesis, arguing that testosterone is primarily involved in status-related behaviours in challenging social interactions, but causal evidence that discriminates between these views is sparse. Here we show that the sublingual administration of a single dose of testosterone in women causes a substantial increase in fair bargaining behaviour, thereby reducing bargaining conflicts and increasing the efficiency of social interactions. However, subjects who believed that they received testosterone-regardless of whether they actually received it or not-behaved much more unfairly than those who believed that they were treated with placebo. Thus, the folk hypothesis seems to generate a strong negative association between subjects' beliefs and the fairness of their offers, even though testosterone administration actually causes a substantial increase in the frequency of fair bargaining offers in our experiment.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: Performance validity test (PVT) research studies commonly utilize a known-groups design, but the criterion grouping approaches within the design vary greatly from one study to another. At ...the present time, it is unclear as to what degree different criterion grouping approaches might impact PVT classification accuracy statistics. Method: To analyze this, the authors used three different criterion grouping approaches to examine how classification accuracy statistics of a PVT (Word Choice Test; WCT) would differ. The three criterion grouping approaches included: (1) failure of 2+ PVTs versus failure of 0 PVTs, (2) failure of 2+ PVTs versus failure of 0-1 PVT, and (3) failure of a stand-alone PVT versus passing of a stand-alone PVT (Test of Memory Malingering). Results: When setting specificity at ≥.90, WCT cutoff scores ranged from 41 to 44 and associated sensitivity values ranged from .64 to .88, depending on the criterion grouping approach that was utilized. Conclusions: When using a stand-alone PVT to define criterion group status, classification accuracy rates of the WCT were higher than expected, likely due to strong correlations between the reference PVT and the WCT. This held true even when considering evidence that this grouping approach results in higher rates of criterion group misclassification. Conversely, when using criterion grouping approaches that utilized failure of 2+ PVTs, accuracy rates were more consistent with expectations. These findings demonstrate that criterion grouping approaches can impact PVT classification accuracy rates and resultant cutoff scores. Strengths, weaknesses, and practical implications of each of the criterion grouping approaches are discussed.
Abstract
Limiting the spread of synthetic genetic information outside of the intended use is essential for applications where biocontainment is critical. In particular, biocontainment of engineered ...probiotics and plasmids that are excreted from the mammalian gastrointestinal tract is needed to prevent escape and acquisition of genetic material that could confer a selective advantage to microbial communities. Here, we built a simple and lightweight biocontainment system that post-translationally activates a site-specific DNA endonuclease to degrade DNA at 18°C and not at higher temperatures. We constructed an orthogonal set of temperature-sensitive meganucleases (TSMs) by inserting the yeast VMA1 L212P temperature-sensitive intein into the coding regions of LAGLIDADG homing endonucleases. We showed that the TSMs eliminated plasmids carrying the cognate TSM target site from laboratory strains of Escherichia coli at the permissive 18°C but not at higher restrictive temperatures. Plasmid elimination is dependent on both TSM endonuclease activity and intein splicing. TSMs eliminated plasmids from E. coli Nissle 1917 after passage through the mouse gut when fecal resuspensions were incubated at 18°C but not at 37°C. Collectively, our data demonstrates the potential of thermoregulated meganucleases as a means of restricting engineered plasmids and probiotics to the mammalian gut.
Graphical Abstract
Graphical Abstract
is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the ...mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in
, and mutations in
result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype. Here, we show that hypervirulent strains containing
mutations can be attenuated with the addition of purine biosynthesis mutations, implicating the necessity for
purine biosynthesis in this phenotype and indicating that
in the mammalian host experiences purine limitation. Using cell culture, we showed that while
mutants are not altered in epithelial cell binding, compared to that of wild-type (WT)
,
mutants have enhanced invasion of these nonprofessional phagocytes, consistent with the requirement of FnBPs for invasion of these cells. This correlates with
mutants having increased transcription of
genes, resulting in higher levels of surface-exposed FnBPs to promote invasion. These data provide important contributions to our understanding of how the pathogenesis of
is affected by sensing of purine levels during infection of the mammalian host.
Monthly plantings of the rice variety Bouake 189 were made under lowland irrigated conditions, to obtain information on the phenological and seasonal occurrence of pests and diseases on the West ...African Rice Development Association (WARDA) research farm near Bouake, Cote d'Ivoire. Regular sampling of insect pests and observations on rice yellow mottle virus (RYMV) disease infection throughout the year provided information on the occurrence of RYMV and potential insect vectors. RYMV incidence and grain yields varied depending on planting date, and for a given planting date, varied from one year to another. There was no evidence that RYMV incidence increases in successive seasons under continuous cropping. There was no significant correlation between RYMV incidence and either rainfall or wind speed. Leaf feeding damage by the beetle vector of RYMV, Trichispa sericea Guerin-Meneville (Coleoptera: Chrysomelidae), and percentage RYMV infected plants were severe in the July and August plantings in 1993, but whereas T. sericea was not observed thereafter, RYMV spread continued. The white leafhoppers Cofana spectra (Distant) and C. unimaculata (Signoret) (Hemiptera: Cicadellidae), the green leafhoppers Nephotettix spp. (Hemiptera: Cicadellidae), the spittle bug Locris rubra F. (Hemiptera: Cercopidae), the diopsids Diopsis longicornis Macquart and D. apicalis Dalman (Diptera: Diopsidae), and the grasshopper Oxy hyla Stal (Orthoptera: Acridadae) were the most abundant of the insect pests and had distinct population peaks within a year. However, population abundances were not correlated with RYMV incidence. The variability of RYMV in time and space and the potential role of weeds as alternative hosts for RYMV are discussed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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