scholarly journals Challenge of investigating biologically relevant functions of virulence factors in bacterial pathogens

2000 ◽  
Vol 355 (1397) ◽  
pp. 643-656 ◽  
Author(s):  
Richard Moxon ◽  
Christoph Tang
Keyword(s):  
Virulence Factors ◽  
Molecular Basis ◽  
Evolutionary Dynamics ◽  
Bacterial Pathogens ◽  
Ecological Factors ◽  
Personal Perspective ◽  
Biologically Relevant ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Recent innovations have increased enormously the opportunities for investigating the molecular basis of bacterial pathogenicity, including the availability of whole–genome sequences, techniques for identifying key virulence genes, and the use of microarrays and proteomics. These methods should provide powerful tools for analysing the patterns of gene expression and function required for investigating host–microbe interactions in vivo. But, the challenge is exacting. Pathogenicity is a complex phenotype and the reductionist approach does not adequately address the eclectic and variable outcomes of host–microbe interactions, including evolutionary dynamics and ecological factors. There are difficulties in distinguishing bacterial ‘virulence’ factors from the many determinants that are permissive for pathogenicity, for example those promoting general fitness. A further practical problem for some of the major bacterial pathogens is that there are no satisfactory animal models or experimental assays that adequately reflect the infection under investigation. In this review, we give a personal perspective on the challenge of characterizing how bacterial pathogens behave in vivo and discuss some of the methods that might be most relevant for understanding the molecular basis of the diseases for which they are responsible. Despite the powerful genomic, molecular, cellular and structural technologies available to us, we are still struggling to come to grips with the question of ‘What is a pathogen?’

scholarly journals Polymers in the gut compress the colonic mucus hydrogel

2016 ◽  
Vol 113 (26) ◽  
pp. 7041-7046 ◽  
Author(s):  
Sujit S. Datta ◽  
Asher Preska Steinberg ◽  
Rustem F. Ismagilov
Keyword(s):  
Thermodynamic Model ◽  
Ex Vivo ◽  
Polymer Concentration ◽  
Dietary Fibers ◽  
Physical Damage ◽  
Gut Microbes ◽  
Specific Pathogen ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host–microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer–mucus interactions can be described using a thermodynamic model based on Flory–Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice—whose microbiota degrade gut polymers—did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.

scholarly journals Longitudinal In Vivo Assessment of Host-Microbe Interactions in a Murine Model of Pulmonary Aspergillosis

iScience ◽  
2019 ◽  
Vol 20 ◽  
pp. 184-194 ◽  
Author(s):  
Shweta Saini ◽  
Jennifer Poelmans ◽  
Hannelie Korf ◽  
James L. Dooley ◽  
Sayuan Liang ◽  
...  
Keyword(s):  
Murine Model ◽  
Pulmonary Aspergillosis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
In Vivo Assessment

scholarly journals A New C-Type Lectin Similar to the Human Immunoreceptor DC-SIGN Mediates Symbiont Acquisition by a Marine Nematode

2006 ◽  
Vol 72 (4) ◽  
pp. 2950-2956 ◽  
Author(s):  
Silvia Bulgheresi ◽  
Irma Schabussova ◽  
Tie Chen ◽  
Nicholas P. Mullin ◽  
Rick M. Maizels ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Marine Nematode ◽  
Mannose Binding Protein ◽  
Mannose Binding ◽  
Marine Symbiosis ◽  
Microbe Interactions ◽  
Sulfur Oxidizing ◽  
Host Microbe Interactions ◽  
Symbiont Acquisition

ABSTRACT Although thiotrophic symbioses have been intensively studied for the last three decades, nothing is known about the molecular mechanisms of symbiont acquisition. We used the symbiosis between the marine nematode Laxus oneistus and sulfur-oxidizing bacteria to study this process. In this association a monolayer of symbionts covers the whole cuticle of the nematode, except its anterior-most region. Here, we identify a novel Ca2+-dependent mannose-specific lectin that was exclusively secreted onto the posterior, bacterium-associated region of L. oneistus cuticle. A recombinant form of this lectin induced symbiont aggregation in seawater and was able to compete with the native lectin for symbiont binding in vivo. Surprisingly, the carbohydrate recognition domain of this mannose-binding protein was similar both structurally and functionally to a human dendritic cell-specific immunoreceptor. Our results provide a molecular link between bacterial symbionts and host-secreted mucus in a marine symbiosis and suggest conservation in the mechanisms of host-microbe interactions throughout the animal kingdom.

scholarly journals Identification of Erwinia amylovora Genes Induced during Infection of Immature Pear Tissue

2005 ◽  
Vol 187 (23) ◽  
pp. 8088-8103 ◽  
Author(s):  
Youfu Zhao ◽  
Sara E. Blumer ◽  
George W. Sundin
Keyword(s):  
Pseudomonas Syringae ◽  
Erwinia Amylovora ◽  
Sequence Similarity ◽  
Type Ii Secretion ◽  
Knockout Mutant ◽  
Technology System ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Blight Disease

ABSTRACT The enterobacterium Erwinia amylovora is a devastating plant pathogen causing necrotrophic fire blight disease of apple, pear, and other rosaceous plants. In this study, we used a modified in vivo expression technology system to identify E. amylovora genes that are activated during infection of immature pear tissue, a process that requires the major pathogenicity factors of this organism. We identified 394 unique pear fruit-induced (pfi) genes on the basis of sequence similarity to known genes and separated them into nine putative function groups including host-microbe interactions (3.8%), stress response (5.3%), regulation (11.9%), cell surface (8.9%), transport (13.5%), mobile elements (1.0%), metabolism (20.3%), nutrient acquisition and synthesis (15.5%), and unknown or hypothetical proteins (19.8%). Known virulence genes, including hrp/hrc components of the type III secretion system, the major effector gene dspE, type II secretion, levansucrase (lsc), and regulators of levansucrase and amylovoran biosynthesis, were upregulated during pear tissue infection. Known virulence factors previously identified in E. (Pectobacterium) carotovora and Pseudomonas syringae were identified for the first time in E. amylovora and included HecA hemagglutinin family adhesion, Peh polygalacturonase, new effector HopPtoCEA, and membrane-bound lytic murein transglycosylase MltEEA. An insertional mutation within hopPtoC EA did not result in reduced virulence; however, an mltE EA knockout mutant was reduced in virulence and growth in immature pears. This study suggests that E. amylovora utilizes a variety of strategies during plant infection and to overcome the stressful and poor nutritional environment of its plant hosts.

scholarly journals Structural basis of ligand selectivity by a bacterial adhesin lectin involved in multi- species biofilm formation

2020 ◽  
Author(s):  
Shuaiqi Guo ◽  
Tyler D.R. Vance ◽  
Hossein Zahiri ◽  
Robert Eves ◽  
Corey Stevens ◽  
...  
Keyword(s):  
High Resolution ◽  
Biofilm Formation ◽  
Molecular Basis ◽  
Symbiotic Bacterium ◽  
Structural Basis ◽  
Ligand Selectivity ◽  
End Groups ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Insight Into

AbstractCarbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here we show MpPA14 binds various monosaccharides, with L-fucose and N-acetyl glucosamine being the strongest ligands (Kd ~ 150 μM). High-resolution structures of MpPA14 with 15 different sugars bound elucidated the molecular basis for the lectin’s apparent binding promiscuity but underlying selectivity. MpPA14 mediates strong Ca2+-dependent interactions with the 3, 4 diols of L-fucopyranose and glucopyranoses, and binds other sugars via their specific minor isomers. Thus, MpPA14 only binds polysaccharides like branched glucans and fucoidans with these free end-groups. Consistent with our findings, adhesion of MpPA14 to diatom cells was selectively blocked by L-fucose, but not by N-acetyl galactosamine. With MpPA14 lectin homologs present in adhesins of several pathogens, our work gives insight into an anti-adhesion strategy to block infection via ligand-based antagonists.

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