Host Adaptation and Immune Modulation Are Mediated by Homologous Recombination in<i>Helicobacter pylori</i>

Robinson, Karen; Loughlin, Michael F.; Potter, Rebecca; Jenks, Peter J.

doi:10.1086/427657

Cited by 36 publications

(35 citation statements)

References 63 publications

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“…Such genomic plasticity is not advantageous for organisms living in stable environments (40). Nevertheless, genomic plasticity increases microdiversity and enables H. pylori to persist in infections (37,39,41). Similarly, it is likely that the high microdiversity reported for deep-sea vent -Proteobacteria (9) results from the genomic plasticity of -Proteobacteria and confers a competitive advantage enabling this lineage to thrive in ever changing steep physical-chemical gradients.…”

Section: Resultsmentioning

confidence: 99%

Deep-sea vent ε-proteobacterial genomes provide insights into emergence of pathogens

Nakagawa¹,

Takaki

Shimamura

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

221

306

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Deep-sea vents are the light-independent, highly productive ecosystems driven primarily by chemolithoautotrophic microorganisms, in particular by -Proteobacteria phylogenetically related to important pathogens. We analyzed genomes of two deep-sea vent -Proteobacteria strains, Sulfurovum sp. NBC37-1 and Nitratiruptor sp. SB155-2, which provide insights not only into their unusual niche on the seafloor, but also into the origins of virulence in their pathogenic relatives, Helicobacter and Campylobacter species. The deep-sea vent -proteobacterial genomes encode for multiple systems for respiration, sensing and responding to environment, and detoxifying heavy metals, reflecting their adaptation to the deep-sea vent environment. Although they are nonpathogenic, both deep-sea vent -Proteobacteria share many virulence genes with pathogenic -Proteobacteria, including genes for virulence factor MviN, hemolysin, invasion antigen CiaB, and the N-linked glycosylation gene cluster. In addition, some virulence determinants (such as the H2-uptake hydrogenase) and genomic plasticity of the pathogenic descendants appear to have roots in deep-sea vent -Proteobacteria. These provide ecological advantages for hydrothermal vent -Proteobacteria who thrive in their deep-sea habitat and are essential for both the efficient colonization and persistent infections of their pathogenic relatives. Our comparative genomic analysis suggests that there are previously unrecognized evolutionary links between important human/animal pathogens and their nonpathogenic, symbiotic, chemolithoautotrophic deepsea relatives.-Proteobacteria ͉ comparative microbial genomics ͉ deep-sea hydrothermal vent ͉ pathogenesis ͉ symbiosis D eep-sea hydrothermal vents are areas on the sea floor of high biological productivity fueled primarily by chemosynthesis. Most of the invertebrates thrive in this hostile environment through their relationship with chemolithoautotrophic proteobacterial symbionts. It has become evident that by far the most prevalent microorganisms at deep-sea vents belong to the -Proteobacteria (1, 2). They often account for Ͼ90% of total rRNA in various hydrothermal habitats as both epi-or endosymbionts of hydrothermal vent invertebrates (3-6) and freeliving organisms associated with actively venting sulfide deposits and in areas where vent fluids and seawater mix [supporting information (SI) Fig. 5] (7-9). Until recently, the metabolic role of these key players in the deep-sea vent ecosystem has remained unknown because of their resistance to cultivation. However, in a recent breakthrough, pure cultures of deep-sea ventProteobacteria provided evidence that the majority of these microbes were mesophilic to thermophilic (capable of growth at 4°C to 70°C) chemolithoautotrophs capable of oxidation of hydrogen and sulfur compounds coupled with the reduction of oxygen, nitrate, and sulfur compounds (9-11). These deep-sea vent -Proteobacteria diverge before their pathogenic relatives in small-subunit rRNA gene trees, and thus comparative genomics can pr...

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Section: Resultsmentioning

confidence: 99%

Deep-sea vent ε-proteobacterial genomes provide insights into emergence of pathogens

Nakagawa¹,

Takaki

Shimamura

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

221

306

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“…Experimental NHPH infections have indeed been shown to evoke a Th2-polarized response (14,16), suggesting that Th2-prone BALB/c mice (27) infected with NHPH can be seen as a critical model for the development of MALT lymphoma induced by NHPH. It has been demonstrated that H. pylori strains mainly stimulate Th1 responses both in humans and in mouse models (28). However, as an exception, the H. pylori strain SS1 does not cause a significant upregulation of gamma interferon (IFN-␥), a signature Th1 marker, in either BALB/c or C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Gastric De Novo Muc13 Expression and Spasmolytic Polypeptide-Expressing Metaplasia during Helicobacter heilmannii Infection

et al. 2014

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bHelicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H ؉ /K ؉ -ATPase ␣/␤ and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.

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“…Furthermore, impaired host colonization of a recombination-deficient Helicobacter pylori mutant strain suggests a functional role for chromosomal rearrangement in H. pylori pathogenesis (29). Like mutator phenotypes, which are observed in some pathogenic species (14,19,20), high-frequency chromosomal rearrangement may provide transient variation for rapid adaptation to a new host environment in host-restricted or niche-adapted strains such as B. pertussis.…”

Section: Discussionmentioning

confidence: 99%

Significant Gene Order and Expression Differences inBordetella pertussisDespite Limited Gene Content Variation

et al. 2006

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Bordetella pertussis, an obligate human pathogen and the agent of whooping cough, is a clonal species, despite the dynamic selection pressures imposed by host immunity and vaccine usage. Because the generation of variation is critical for species evolution, we employed a variety of approaches to examine features of B. pertussis genetic variation. We found a high level of conservation of gene content among 137 B. pertussis strains with different geographical, temporal, and epidemiological associations, using comparative genomic hybridization. The limited number of regions of difference were frequently located adjacent to copies of the insertion element IS481, which is present in high numbers in the B. pertussis chromosome. This repeated sequence appears to provide targets for homologous recombination, resulting in deletion of intervening sequences. Using subtractive hybridization, we searched for previously undetected genes in diverse clinical isolates but did not detect any new genes, indicating that gene acquisition is rare in B. pertussis. In contrast, we found evidence of altered gene order in the several strains that were examined and again found an association of IS481 with sites of rearrangement. Finally, we compared whole-genome expression profiles of different strains and found significant changes in transcript abundance, even in the same strain after as few as 12 laboratory passages. This combination of approaches provides a detailed picture of a pathogenic species with little gene loss or gain but with the capacity to generate variation by rearranging its chromosome and altering gene expression. These findings have broad implications for host adaptation by microbial pathogens.Bacterial pathogens face a dynamic array of selective pressures as they establish themselves within hosts, replicate, and are transmitted to new hosts. Upon arrival in a host, microbes may be forced to contend with innate immune defenses, scarcity of metabolic resources, competition from other bacteria for resources and colonization sites, and adaptive immunity, and then they must readapt to the outside environment during transmission to a new host. Individual hosts and pathogens adapt and respond to each other during the course of an infection, while evolving new offensive and defensive strategies on a population-wide basis. Pathogens must employ strategies to prevent their eradication by host immunity, which is constantly changing both within an individual host and within the host population. For an obligate pathogen to persist in a host population, its evolutionary process must be ongoing. This evolution can include gaining new functionality through horizontal transfer of genes, losing "antivirulence" genes, or altering the form or regulation of existing proteins through mutation in coding sequences or changes in promoters or operonic structures.The Bordetella genus of respiratory pathogens provides a rich model with which to explore questions of evolution of pathogenesis and host adaptation. The three species comprising the "c...

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Host Adaptation and Immune Modulation Are Mediated by Homologous Recombination inHelicobacter pylori

Cited by 36 publications

References 63 publications

Deep-sea vent ε-proteobacterial genomes provide insights into emergence of pathogens

Deep-sea vent ε-proteobacterial genomes provide insights into emergence of pathogens

Gastric De Novo Muc13 Expression and Spasmolytic Polypeptide-Expressing Metaplasia during Helicobacter heilmannii Infection

Significant Gene Order and Expression Differences inBordetella pertussisDespite Limited Gene Content Variation

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