scholarly journals Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of α-1 antitrypsin

2011 ◽  
Vol 434 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Louise Meinert Niclasen ◽  
Johan G. Olsen ◽  
Robert Dagil ◽  
Zhang Qing ◽  
Ole E. Sørensen ◽  
...  

The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of SpeB to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (α-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced contact system activation, supported by increased bacterial growth in prekallikrein deficient plasma. In a mouse model of systemic infection, administration of SpeB reduced significantly bacterial dissemination. The findings reveal an additional layer of complexity to host–microbe interactions that may be of benefit in the treatment of severe bacterial infections.

2020 ◽  
Author(s):  
Hannah M. McMillan ◽  
Sophia G. Zebell ◽  
Jean B. Ristaino ◽  
Xinnian Dong ◽  
Meta J. Kuehn

SummaryBacterial outer membrane vesicles (OMVs) perform a variety of functions in bacterial survival and virulence. In mammalian systems, OMVs activate immune responses and have been exploited as vaccines. However, little work has focused on the role that OMVs play during interactions with plant hosts. Here we report that OMVs from the pathogenic Pseudomonas syringae and the beneficial Pseudomonas fluorescens activate plant immune responses that protect against bacterial and oomycete pathogens. OMVs from these two species display different sensitivity to biochemical stressors, which could indicate differences in OMV cargo packaging. Furthermore, our study shows that OMV-induced protective immune responses are T3SS- and protein-independent, while OMV-mediated seedling growth inhibition largely depends on protein cargo. Importantly, OMV-mediated plant responses are distinct from those triggered by PAMP/MAMPs or effector molecules alone. OMVs provide a unique opportunity to study virulence factors in combination and add a new layer of interaction and complexity to host-microbe interactions.


2021 ◽  
Author(s):  
Karthik Hullahalli ◽  
Justin R. Pritchard ◽  
Matthew K. Waldor

AbstractPathogen population dynamics during infection are critical determinants of infection susceptibility and define patterns of dissemination. However, deciphering pathogen population dynamics, particularly founding population sizes in host organs and patterns of dissemination between organs, is difficult due to the fact that measuring bacterial burden alone is insufficient to observe these patterns. Introduction of allelic diversity into otherwise identical bacteria using DNA barcodes enables sequencing-based measurements of these parameters, in a method known as STAMP (Sequence Tag-Based analysis of Microbial Population dynamics). However, bacteria often undergo unequal expansion within host organs, resulting in marked differences in the frequencies of barcodes in input and output libraries. Here, we show that these differences confound STAMP-based analyses of founding population sizes and dissemination patterns. We present STAMPR, a successor to STAMP that accounts for such population expansions. Using data from systemic infection of barcoded Extraintestinal Pathogenic E. coli we show that this new framework along with the metrics it yields enhances the fidelity of measurements of bottlenecks and dissemination patterns. STAMPR was also validated on an independent, barcoded Pseudomonas aeruginosa dataset, uncovering new patterns of dissemination within the data. This framework (available at https://github.com/hullahalli/stampr_rtisan), when coupled with barcoded datasets, enables a more complete assessment of within-host bacterial population dynamics.ImportanceBarcoded bacteria are often employed to monitor pathogen population dynamics during infection. The accuracy of these measurements is diminished by unequal bacterial expansion rates. Here, we develop computational tools to circumvent this limitation and establish additional metrics that collectively enhance the fidelity of measuring within-host pathogen founding population sizes and dissemination patterns. These new tools will benefit future studies of the dynamics of pathogens and symbionts within their respective hosts, and may have additional barcode-based applications beyond host-microbe interactions.


2021 ◽  
Author(s):  
Sumnima Singh ◽  
Patricia Bastos-Amador ◽  
Jessica A. Thompson ◽  
Mauro Truglio ◽  
Bahtiyar Yilmaz ◽  
...  

AbstractGenes encoding certain glycosyltransferases are thought to be under relatively high selection pressure, due to the involvement of the glycans that they synthesize in host-microbe interactions. Here we used a mouse model to investigate whether the loss of α-1,3-galactosyltransferase (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) expression during primate evolution might have affected host-microbiota interactions. We found that Ggta1 deletion in mice shaped the composition of the gut microbiota in relation to the bacterial species present. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with IgA targeting of αGal-expressing bacteria. Systemic infection by the Ig-shaped microbiota elicited a less severe form of sepsis than infection with the non-Ig-shaped microbiota. This suggests that in the absence of host αGal, the microbiota is shaped towards lower pathogenicity, likely providing a fitness gain to the host. We infer that high selection pressure exerted by bacterial sepsis may have contributed to increase frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.


mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Gargi Kulkarni ◽  
Nicolas Busset ◽  
Antonio Molinaro ◽  
Daniel Gargani ◽  
Clemence Chaintreuil ◽  
...  

ABSTRACTA better understanding of how bacteria resist stresses encountered during the progression of plant-microbe symbioses will advance our ability to stimulate plant growth. Here, we show that the symbiotic system comprising the nitrogen-fixing bacteriumBradyrhizobium diazoefficiensand the legumeAeschynomene afrasperarequires hopanoid production for optimal fitness.While methylated (2Me) hopanoids contribute to growth under plant-cell-like microaerobic and acidic conditions in the free-living state, they are dispensable during symbiosis. In contrast, synthesis of extended (C35) hopanoids is required for growth microaerobically and under various stress conditions (high temperature, low pH, high osmolarity, bile salts, oxidative stress, and antimicrobial peptides) in the free-living state and also during symbiosis. These defects might be due to a less rigid membrane resulting from the absence of free or lipidA-bound C35hopanoids or the accumulation of the C30hopanoid diploptene. Our results also show that C35hopanoids are necessary for symbiosis only with the hostAeschynomene afrasperabut not with soybean. This difference is likely related to the presence of cysteine-rich antimicrobial peptides inAeschynomenenodules that induce drastic modification in bacterial morphology and physiology. The study of hopanoid mutants in plant symbionts thus provides an opportunity to gain insight into host-microbe interactions during later stages of symbiotic progression, as well as the microenvironmental conditions for which hopanoids provide a fitness advantage.IMPORTANCEBecause bradyrhizobia provide fixed nitrogen to plants, this work has potential agronomical implications. An understanding of how hopanoids facilitate bacterial survival in soils and plant hosts may aid the engineering of more robust agronomic strains, especially relevant in regions that are becoming warmer and saline due to climate change. Moreover, this work has geobiological relevance: hopanes, molecular fossils of hopanoids, are enriched in ancient sedimentary rocks at discrete intervals in Earth history. This is the first study to uncover roles for 2Me- and C35hopanoids in the context of an ecological niche that captures many of the stressful environmental conditions thought to be important during (2Me)-hopane deposition. Though much remains to be done to determine whether the conditions present within the plant host are shared with niches of relevance to the rock record, our findings represent an important step toward identifying conserved mechanisms whereby hopanoids contribute to fitness.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Patrick R. Secor ◽  
Ajai A. Dandekar

ABSTRACT Bacteria harbor viruses called bacteriophages that, like all viruses, co-opt the host cellular machinery to replicate. Although this relationship is at first glance parasitic, there are social interactions among and between bacteriophages and their bacterial hosts. These social interactions can take on many forms, including cooperation, altruism, and cheating. Such behaviors among individuals in groups of bacteria have been well described. However, the social nature of some interactions between phages or phages and bacteria is only now becoming clear. We are just beginning to understand how bacteriophages affect the sociobiology of bacteria, and we know even less about social interactions within bacteriophage populations. In this review, we discuss recent developments in our understanding of bacteriophage sociobiology, including how selective pressures influence the outcomes of social interactions between populations of bacteria and bacteriophages. We also explore how tripartite social interactions between bacteria, bacteriophages, and an animal host affect host-microbe interactions. Finally, we argue that understanding the sociobiology of bacteriophages will have implications for the therapeutic use of bacteriophages to treat bacterial infections.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sumnima Singh ◽  
Patricia Bastos-Amador ◽  
Jessica Ann Thompson ◽  
Mauro Truglio ◽  
Bahtiyar Yilmaz ◽  
...  

Genes encoding glycosyltransferases can be under relatively high selection pressure, likely due to the involvement of the glycans synthesized in host-microbe interactions. Here, we used mice as an experimental model system to investigate whether loss of α−1,3-galactosyltransferase gene (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) glycan expression affects host-microbiota interactions, as might have occurred during primate evolution. We found that Ggta1 deletion shaped the composition of the gut microbiota. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with targeting of αGal-expressing bacteria by IgA. Systemic infection with an Ig-shaped microbiota inoculum elicited a less severe form of sepsis compared to infection with non-Ig-shaped microbiota. This suggests that in the absence of host αGal, antibodies can shape the microbiota towards lower pathogenicity. Given the fitness cost imposed by bacterial sepsis, we infer that the observed reduction in microbiota pathogenicity upon Ggta1 deletion in mice may have contributed to increase the frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.


2009 ◽  
Vol 4 (10) ◽  
pp. 457-462 ◽  
Author(s):  
Sebastian Fraune ◽  
Thomas C. G. Bosch ◽  
René Augustin

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