Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis

Carey, Clayton M.; Apple, Sarah E.; Hilbert, Zoë A.; Kay, Michael S.; Elde, Nels C.

doi:10.1101/2020.03.29.014761

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Beyond immune evasion and nutrient acquisition, bacteria encode a wide variety of virulence factors that could also give rise to conflicts. Recent work has provided evidence of repeated adaptation among host proteins targeted by bacterial toxins [ 48 , 49 ], consistent with this hypothesis. Given that many bacterial virulence factors are also encoded by related commensal microbes, pathogen-driven conflicts could also hold the potential to restrict the host species tropism of commensal members of the microbiota.…”

Section: What Are Emerging Questions Regarding Bacterial–host Evolutisupporting

confidence: 56%

Battlefronts of evolutionary conflict between bacteria and animal hosts

Aleru

Barber

2020

PLoS Pathog

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Conflict is pervasive in nature, as observed in the struggle between predators and prey, competition for mates, as well as between pathogenic microbes and their hosts. The burden imposed by pathogens can place strong selective pressure on host populations to evolve resistance to infection [1]. Conversely, host immune responses promote the repeated evolution of defensive countermeasures by microbial pathogens. This antagonism can give rise to evolutionary conflicts, including "Red Queen" dynamics, in which pathogens and hosts are forced to continually adapt to maximize their relative fitness (Fig 1) [2,3]. Consistent with the existence of such conflicts, immune system components have been shown to be among the most rapidly evolving genes in animal genomes [4-7]. These observations can reflect the rapid spread of new beneficial mutations in populations over time, a process termed positive selection. Unique genetic signatures are used to infer positive selection between and within species, including elevated rates of nonsynonymous nucleotide substitutions relative to synonymous substitutions in protein-coding genes (also termed dN/dS or ω), as well as to measure the loss of genetic variation around a locus associated with a recent selective sweep. Genomic studies further support the long-held theory that host-pathogen interactions are major drivers of natural selection and adaptation across diverse taxa [4,6-8]. The past 15 years have seen a powerful integration of genetic and experimental approaches to identify instances of host-pathogen conflict as well as empirically test how conflicts shape immunity and disease [9]. Such approaches have pinpointed new molecular functions underlying host defense [10,11], identified completely new genes or pathways involved in disease susceptibility [12,13], and revealed new determinants of pathogen tropism [14-16]. Hostpathogen evolutionary conflicts thus provide powerful systems for dissecting mechanisms of infectious disease pathogenesis. How have host immune defenses been shaped by evolutionary conflicts with bacteria? An established and growing body of work has characterized instances of evolutionary conflict between animals and viruses [5,9]. More recently, studies have begun to emerge revealing molecular details of conflicts driven by cellular pathogens including bacteria, fungi, and parasites. Below, we highlight recent advances in our understanding of evolutionary conflicts between animal hosts and pathogenic bacteria (Fig 2), as well as discuss future areas of study in this burgeoning field.

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Section: What Are Emerging Questions Regarding Bacterial–host Evolutisupporting

confidence: 56%

Battlefronts of evolutionary conflict between bacteria and animal hosts

Aleru

Barber

2020

PLoS Pathog

View full text Add to dashboard Cite

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Guanylyl Cyclase C As A Biomarker for Immunotherapies for the Treatment of Gastrointestinal Malignancies

et al. 2021

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Gastrointestinal cancers encompass a diverse class of tumors arising in the GI tract, including esophagus, stomach, pancreas and colorectum. Collectively, gastrointestinal cancers compose a high fraction of all cancer deaths, highlighting an unmet need for novel and effective therapies. In this context, the transmembrane receptor guanylyl cyclase C (GUCY2C) has emerged as an attractive target for the prevention, detection and treatment of many gastrointestinal tumors. GUCY2C is an intestinally-restricted protein implicated in tumorigenesis that is universally expressed by primary and metastatic colorectal tumors as well as ectopically expressed by esophageal, gastric and pancreatic cancers. This review summarizes the current state of GUCY2C-targeted modalities in the management of gastrointestinal malignancies, with special focus on colorectal cancer, the most incident gastrointestinal malignancy.

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Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis

Cited by 2 publications

References 26 publications

Battlefronts of evolutionary conflict between bacteria and animal hosts

Battlefronts of evolutionary conflict between bacteria and animal hosts

Guanylyl Cyclase C As A Biomarker for Immunotherapies for the Treatment of Gastrointestinal Malignancies

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