Host-pathogen interactions: a diversity of themes, a variety of molecular machines.
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Actins↗
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Results for “Pathogen diversity”
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Pathogen-driven forest diversity.
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Animals↗
Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro.
Mutational dysfunction of PARKIN gene, which encodes a double RING finger protein and has ubiquitin ligase E3 activity, is the major cause of autosomal recessive juvenile Parkinsonism. Although many studies explored the functions of Parkin, its biochemical character is poorly understood. To address this issue, we established an E3 assay system using maltose-binding protein-fused Parkin purified from Escherichia coli. Using this recombinant Parkin, we found that not the front but the rear RING finger motif is responsible for the E3 activity of Parkin, and it catalyzes multiple monoubiquitylation. Intriguingly, for autosomal recessive juvenile Parkinsonism-causing mutations of Parkin, whereas there was loss of E3 activity in the rear RING domain, other pathogenic mutants still exhibited E3 activity equivalent to that of the wild-type Parkin. The evidence presented allows us to reconsider the function of Parkin-catalyzed ubiquitylation and to conclude that autosomal recessive juvenile Parkinsonism is not solely attributable to catalytic impairment of the E3 activity of Parkin.
Amino Acid Motifs↗
Structural and sequence diversity of the pathogenicity island of uropathogenic Escherichia coli which encodes the USP protein.
A total of 321 uropathogenic Escherichia coli (UPEC) strains and 12 strains of E. coli isolated from stool samples of healthy individuals, which were previously shown to be positive in colony hybridization test using the usp (encoding for the uropathogenic-specific protein) DNA probe, were examined by PCR amplification to determine the size of the usp gene and the pathogenicity island (PI). Three types of size variation were observed for the usp gene and four types for the PI. Sequencing analysis of the PIs from seven representative strains (six UPEC and one from a normal healthy individual) revealed that the usp genes can be classified into two groups, each having different sequences in the 3'-terminal region. The peptides encoded by the three open reading frames (ORFs) downstream of usp had identical 23 amino acid residues in the C-terminal region. The subregion encoding these small ORFs has a mosaic structure constituted of six segments. The positions of these segments vary from strain to strain, and in some strains, two to four segments are deleted. This indicates that rearrangements occur frequently in this region and the mosaic arrangement apparently contributes to the size variation observed in the PCR examination of the usp genes and PIs.
Amino Acid Sequence↗
Diverse bacteria are pathogens of Caenorhabditis elegans.
Practically and ethically attractive as model systems, invertebrate organisms are increasingly recognized as relevant for the study of bacterial pathogenesis. We show here that the nematode Caenorhabditis elegans is susceptible to a surprisingly broad range of bacteria and may constitute a useful model for the study of both pathogens and symbionts.
Aeromonas hydrophila↗
Diversity among xanthomonads pathogenic on pepper and tomato.
Xanthomonas campestris pv. vesicatoria, causal agent of bacterial spot of tomato and pepper, had been considered for nearly 70 years to be a relatively homogeneous organism. However, in the past decade this bacterium was determined to be composed of two genetically and phenotypically distinct groups. The two groups, designated A and B, were distinguished based on amylolytic activity, expression of unique protein bands, reaction on differential hosts (tomato races T1 and T2), reaction patterns with monoclonal antibodies, DNA restriction profiles, and DNA:DNA hybridization. The A and B groups were placed into X. axonopodis pv. vesicatoria and X. vesicatoria, respectively. A third group, designated C, was pathogenically (race T3) and serologically distinct from A and B strains, and formed unique DNA restriction profiles. DNA:DNA hybridization data suggest that C is distinct but related to A strains and may represent a subspecies of A. A final group, designated D, consisted of X. gardneri, an organism identified in Yugoslavia in 1957, and also found in Costa Rica. Group D was determined to be genetically distinct from strains within the other two groups; it represents a third Xanthomonas species pathogenic on tomato and pepper.
Journal Article↗
The diversity of bacterial pathogenicity mechanisms.
A report on the international conference 'Molecular basis of bacterial pathogenesis', sponsored by the Federation of European Microbiological Societies (FEMS) and the Israel Center for the Study of Emerging Diseases, Ein Gedi, Israel, 23-27 January 2005.
Bacteria↗
Strategies by which some pathogenic trichomonads integrate diverse signals in the decision-making process.
The interaction between each one of Trichomonas vaginalis and Tritrichomonas foetus with their hosts is a complex process in which components associated to the cell surfaces of both parasites and host epithelial cells, and also to soluble components found in vaginal/urethral secretions, are involved. Either cytoadhesion or the cytotoxicity exerted by parasites to host cells can be dictated by virulence factors such as adhesins, cysteine proteinases, laminin-binding proteins, integrins, integrin-like molecules, a cell detachment factor, a pore-forming protein, and glycosidases among others. How trichomonads manipulate informations from the extracellular medium, transduce such informations, and respond to them by stimulating the activities of some surface molecules and/or releasing enzymes are the aspects concerning trichomonal virulence which are here briefly reviewed and discussed.
Animals↗
Occurrence and diversity of egg pathogenic fungi of the Mediterranean cereal cyst nematode Heterodera latipons.
Eighteen fungal strains in nine genera present in German and Syrian soils were isolated from eggs of the barley cyst nematode H. latipons. The fungi were selected out of the soil microflora using the slide-frame baiting technique from a semiarid soil originating from Syria heavily infested with H. latipons and from a temperate soil from German heavily infested with H. schachtii. Fusarium and Acremonium were the most common fungi isolated from the both soils. The natural suppressiveness or antagonistic potential of egg pathogenic fungi in the Syrian and German soils toward H. latipons also was measured. The results demonstrated that a higher level of antagonistic potential and a greater level of fungal egg pathogen biodiversity is present in the semiarid Syrian soils. This is important for the natural control of the Mediterranean cereal cyst nematode H. latipons which is widely spread throughout the region. The high level of biodiversity in the soil may allow subsequent buffering of the pest even when unsuitable soil conditions for growth of the antagonistic fungi occur e.g. low organic matter, as is common in the semiarid soils of the Middle East. These isolates may also lend themselves to management in the field or to inundative approaches to biocontrol of cereal cyst nematodes in the semiarid production zone.
Acremonium↗
Bacteria associated with crabs from cold waters with emphasis on the occurrence of potential human pathogens.
A diverse array of bacterial species, including several potential human pathogens, was isolated from edible crabs collected in cold waters. Crabs collected near Kodiak Island, Alaska, contained higher levels of bacteria than crabs collected away from regions of human habitation. The bacteria associated with the crabs collected near Kodiak included Yersinia enterocolitica, Klebsiella pneumoniae, and coagulase-negative Staphylococcus species; the pathogenicity of these isolates was demonstrated in mice. Although coliforms were not found, the bacterial species associated with the tissues of crabs collected near Kodiak indicate possible fecal contamination that may have occurred through contact with sewage. Compared with surrounding waters and sediments, the crab tissues contained much higher proportions of gram-positive cocci. As revealed by indirect plate counts and direct scanning electron microscopic observations, muscle and hemolymph tissues contained much lower levels of bacteria than shell and gill tissues. After the death of a crab, however, the numbers of bacteria associated with hemolymph and muscle tissues increased significantly. Microcosm studies showed that certain bacterial populations, e.g., Vibrio cholerae, can be bioaccumulated in crab gill tissues. The results of this study indicate the need for careful review of waste disposal practices where edible crabs may be contaminated with microorganisms that are potential human pathogens and the need for surveillance of shellfish for pathogenic microorganisms that naturally occur in marine ecosystems.
Alaska↗
Mutation and recombination in Helicobacter pylori: mechanisms and role in generating strain diversity.
The pathogenic bacterium Helicobacter pylori infects half of the human population and it is one of the most genetically diverse bacterial species known. The unusual combination of high frequencies of mutation and recombination events together with a very small size of DNA fragments imported into the genome after recombination, contribute to its genetic variability. In this review article, we discuss the genetic variability of H. pylori, the mechanisms that generate diversity, and the potential relevance of genetic variability to colonization and pathogenicity.
DNA Repair↗
Emerging food- and waterborne pathogen Arcobacter in wastewater: diversity and antibiotic resistance.
Arcobacter spp. are emerging food- and waterborne pathogens frequently detected in wastewater. Despite their high abundance in wastewater, Arcobacter diversity, antibiotic resistance, and genomic traits remain poorly characterized. To address these knowledge gaps, we conducted a comprehensive study of Arcobacter spp. in influent, effluent, and activated sludge from a Finnish wastewater treatment plant using full-length 16S rRNA gene sequencing, isolate-based genomics, and phenotypic antibiotic susceptibility testing. Arcobacter spp. were highly abundant in raw sewage but substantially removed during treatment. Four Arcobacter species were identified, dominated by Arcobacter cryaerophilus and Arcobacter suis. A proportion of amplicon sequence variants unclassified to species-level revealed potentially unexplored Arcobacter diversity. For the first time, we observed intragenomic variability in 16S rRNA gene copies of A. cryaerophilus, highlighting the importance of integrating culture-based and culture-independent approaches. Phenotypic testing revealed high proportions of non-wild-type isolates for clinically relevant antibiotics, including ampicillin, cefotaxime, tetracycline, and erythromycin. Genomic analyses showed that antibiotic resistance profiles were primarily mediated by chromosomally encoded determinants, including β-lactamases, efflux systems, and point mutations. Additionally, a broad arsenal of chromosomal and plasmid-borne resistance genes to heavy metals, biocides, and organic solvents was detected, reflecting adaptations to the wastewater environment. These findings provide novel insights into Arcobacter species-level diversity, resistance mechanisms, and ecological adaptations in anthropogenically influenced environments. The study highlights the significance of Arcobacter for public health and establishes a foundation for further research.IMPORTANCEArcobacter spp. are emerging human and animal pathogens that exhibit increasing resistance to clinically relevant antibiotics. Most community-acquired infections are linked to exposure through contaminated food and water, yet studies investigating their occurrence and diversity in wastewater remain scarce. Here, we focus on wastewater as an abundant source of Arcobacter spp. and a potential dissemination route contributing to downstream contamination of surface waters, irrigated soils, and possibly the food chain. By characterizing the species-level diversity, genomic traits, and antibiotic resistance profiles of Arcobacter spp. in wastewater, this study provides critical insights into the ecology and epidemiology of this ubiquitous genus.
Arcobacter↗
Actin-based motility of intracellular microbial pathogens.
A diverse group of intracellular microorganisms, including Listeria monocytogenes, Shigella spp., Rickettsia spp., and vaccinia virus, utilize actin-based motility to move within and spread between mammalian host cells. These organisms have in common a pathogenic life cycle that involves a stage within the cytoplasm of mammalian host cells. Within the cytoplasm of host cells, these organisms activate components of the cellular actin assembly machinery to induce the formation of actin tails on the microbial surface. The assembly of these actin tails provides force that propels the organisms through the cell cytoplasm to the cell periphery or into adjacent cells. Each of these organisms utilizes preexisting mammalian pathways of actin rearrangement to induce its own actin-based motility. Particularly remarkable is that while all of these microbes use the same or overlapping pathways, each intercepts the pathway at a different step. In addition, the microbial molecules involved are each distinctly different from the others. Taken together, these observations suggest that each of these microbes separately and convergently evolved a mechanism to utilize the cellular actin assembly machinery. The current understanding of the molecular mechanisms of microbial actin-based motility is the subject of this review.
Actins↗
Understanding Mycobacterium tuberculosis through its genomic diversity and evolution.
Pathogen evolution and genomic diversity are shaped by specific host immune pressures and therapeutic interventions. Analysis of the extant genomes of circulating strains of Mycobacterium tuberculosis, a leading cause of infectious mortality that has co-evolved with humans for thousands of years, can provide new insights into host-pathogen interactions that underlie specific aspects of pathogenesis and onward transmission. With the explosion in the number of fully sequenced M. tuberculosis strains that are now paired with detailed clinical data, there are new opportunities to understand the evolutionary basis for and consequences of M. tuberculosis strain diversity. This review examines mechanistic findings that have emerged from pairing whole genome sequencing data and evolutionary analysis with functional dissection of specific bacterial variants. These include improved understanding of secreted effectors that modulate the properties and migratory behavior of infected macrophages as well as bacterial genetic alterations important for survival within hypoxic microenvironments. Genomic, evolutionary, and functional analyses across diverse M. tuberculosis strains will identify prominent bacterial adaptations to their human hosts and shape our understanding of TB disease biology and the host immune response.
Mycobacterium tuberculosis↗
Genetic Diversity among Xanthomonas campestris Strains Pathogenic for Small Grains.
A collection of 51 Xanthomonas campestris strains from throughout the world was studied to detect and assess genetic diversity among pathogens of small grains. Isolates from barley, bread wheat, bromegrass, canary grass, cassava, maize, orchard grass, rice, rough-stalked meadow grass, rye, timothy, and triticale were analyzed by pathogenicity tests on bread wheat cv. Alondra and barley cv. Corona, indirect immunofluorescence, and restriction fragment length polymorphism (RFLP). Three probes were used for the RFLP analysis. They were an acetylaminofluorene-labelled 16S+23S rRNA probe from Escherichia coli and two (sup32)P-labelled restriction fragments from either plasmidic (pBSF2) or chromosomal (pBS8) DNA of X. campestris pv. manihotis. Strains clustered in 9 and 20 groups with the rRNA probe and the pBSF2 DNA probe, respectively. Strains of X. campestris pv. graminis, X. campestris pv. phleipratensis, and X. campestris pv. poae are shown to be related but are also distinguishable by RFLP patterns, serology, and pathogenicity on bread wheat. Strains pathogenic only for barley and not for wheat grouped together. Another group is temporarily designated deviant X. campestris pv. undulosa. These South American isolates from bread wheat did not react by indirect immunofluorescence and produced atypical lesions in pathogenicity tests. The results stress the need to perform pathogenicity tests before strains are named at the pathovar level. The importance of the different probes used for epidemiological studies or phylogenetic studies of closely related strains is underlined.
Journal Article↗
Genetic heterogeneity and pathogenic potential of historical Crimean-Congo hemorrhagic fever virus isolates in China.
The Crimean-Congo hemorrhagic fever virus (CCHFV) poses a significant public health threat. In China, CCHFV has been circulating for decades, yet the genomic diversity and pathogenic potential of the circulating strains remain poorly characterized, hindering risk assessment and countermeasure development. In this study, we recovered 24 historical CCHFV strains isolated between 1966 and 2004 from humans, ticks and jerboas in Xinjiang Uyghur Autonomous Region of China. Whole-genome sequencing was performed, followed by comprehensive analyses of their phylogenetic relationships, in vitro infectivity and in vivo pathogenicity. Phylogenetic analyses revealed high genetic heterogeneity, identifying seven genotypes for the L segment, nine for the M segment (including a novel Asia 4 genotype), and nine for the S segment. Amino acid mutation analysis revealed that the mucin-like domain (MLD) of the glycoprotein (GP) exhibited the highest mutation rate, contributing substantially to sequence diversity. In vitro, Asia 2 (75024) and Asia 3 (79121M18) strains exhibited robust replication in monkey-, hamster-, and human-derived cell lines. In C57BL/6 mice, all four representative strains induced viral replication and specific antibody responses (IgM and IgG), causing mild to moderate pathological damage in the liver, spleen, and kidneys. In IFNAR-/- mice, virulence varied markedly among representative strains: Asia 2 and Asia 3 strains were highly lethal (LD50 < 1 TCID50), Asia 1 was moderately virulent (LD50 = 142.5 TCID50), and Asia 4 exhibited atypical, non-dose-dependent mortality. Collectively, our work reports a novel Asia 4 genotype and suggests strain- and lineage-associated differences in virulence for CCHFV in China, providing critical insights for surveillance and targeted countermeasure development.
Animals↗
Clinical presentation in relation to diversity within the Helicobacter pylori cag pathogenicity island.
OBJECTIVE: This study investigated the genetic diversity of the cag pathogenicity island (PAI) in Helicobacter pylori (H. pylori) in relation to clinical outcome and interleukin (IL)-8 production. METHODS: Seven genes in the cag PAI (cagA, cagE, cagG, cagM, cagT, open reading frame 13 and 10) were examined by polymerase chain reaction and Southern blot hybridization using H. pylori from 120 patients with different presentations (duodenal ulcer, gastric cancer, gastritis alone). IL-8 production from AGS cells (gastric cancer cell line) cocultured with H. pylori was measured by ELISA. RESULTS: An intact cag PAI was present in 104 (87%) isolates, and five (4%) had deletions within the cag PAI; 11 (9%) lacked the entire cag PAI. Clinical isolates containing the complete cag PAI induced a greater secretion of IL-8 as compared with those without the cag PAI (3048 +/- 263 vs 480 +/- 28 pg/ml, p < 0.001). Deletion of only cagG reduced IL-8 secretion by two thirds. Deletions of more than one locus reduced IL-8 secretion to background. A similar proportion of H. pylori from patients with gastritis, duodenal ulcer, or gastric cancer had intact cag PAI (88%, 88%, and 85%, respectively). Although the presence of cagG was a better predictor of the presence of an intact cag PAI than cagA or cagE, the presence or absence of any of these genes had no association with clinical presentation. CONCLUSION: Although the cag PAI plays an important role in IL-8 production, clinical presentation cannot be predicted by the presence of an intact cag PAI or any of these seven cag PAI genes.
Adult↗
Selective delivery of antigens by recombinant bacteria.
The means to attenuate Salmonella and to endow such avirulent strains with the ability to express colonization and virulence antigens from other pathogens has achieved considerable progress during the past several years. One can therefore begin to design and construct strains with specificity to a given animal host and to express in a defined way specific colonization and virulence antigens in a manner to stimulate long-lasting immunity to the Salmonella and to the pathogen supplying the genetic information for the colonization and virulence antigens. Since most pathogens colonize on or invade through mucosal surfaces, the use of recombinant bivalent Salmonella vaccine strains to stimulate a mucosal immune response would induce the development of a first line of defense against a diversity of pathogens. Mucosal immunity should therefore reduce contagious spread of many pathogens since the dose to overcome the mucosal immune barrier would be increased to result in a diminished likelihood of infection. The fact that the recombinant Salmonella vaccine strains also induce humoral and cellular immune responses justifies their use for induction of long-lasting immunity. Although considerable progress has been made in targeting antigens to the GALT by use of avirulent Salmonella, a similar strategy for delivery of antigens to the BALT has yet to be discovered and developed. In addition to constituting a system for induction of immunity against a diversity of pathogens, the recombinant avirulent Salmonella system should provide a means to explore parameters of the mucosal immune response. This would include investigation of the location and duration of memory, the age dependence of induction of mucosal immunity, and the means for the possible induction of oral tolerance with regard to either the mucosal or humoral response to an antigen expressed by the recombinant Salmonella. It is also possible to contemplate using the avirulent Salmonella to target expression of various modulators of the immune system such as interleukin-2 and interferon-gamma to the GALT and thus further enhance the immune response. Lastly, one can introduce into avirulent Salmonella strains genes for putative colonization antigens in order to investigate whether induction of an immune response against the putative colonization antigen does or does not interfere with infection. This system, therefore, permits another means to analyze the relative importance of various bacterial surface attributes in conferring pathogenicity to the microbe.
Animals↗