Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution.

Bruno Cavadas,Marcelo Correia,Joana Melo,Ana C Magalhães,Valdemar Máximo,Ceu Figueiredo,Luísa Pereira,Rui Camacho,Marina Leite,Nicole Pedro,Nuno A Fonseca

doi:10.3390/microorganisms9020240

Abstract

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

Highlights

By applying a genome-wide approach to the host transcriptome, supported by some functional confirmations, in controlled double-ancestry host–pathogen in vitro settings, we were able to provide experimental evidence to address three main questions: (1) do the host responses to H. pylori infection, in terms of whole-genome expression profile, differ between human ancestries; (2) are coevolution model expectations fulfilled, with higher adaptation of the African ancestry to H. pylori infection, and maladaptation of European and Asian populations groups; and (3) do infections caused by a mismatched H. pylori ancestry differ from a matched setting?
Our results clearly show that a higher number of genes were significantly changed upon infection in the African and Asian cell lines than in the European (≈5 to 10 times), indicating a more complex response to the infection stimulus
The top activated pathways differed between human ancestries: African up-regulated lipid metabolism, while Asian activated energy production, contrary to European which relied on immune-related pathways as the most up-regulated

Summary

Introduction

Coevolution is a biological term coined in 1964 by Ehrlich and Raven [1] to describe relationships between two entities where selective pressures are exerted on each other’s evolution. Coevolution occurs in many forms of mutualism, host–parasite, and predatorprey relationships, as well as competition within or between species. The most extreme examples of exquisite adaptation, displaying evidence of tightly coevolved morphology, physiology, and behavior, are the symbiotic integrations of mitochondria and chloroplasts in eukaryotic cells [2]. Improvements in mathematical models [3] have been showing that the expected stable adaptive peaks attainable through coevolution are rarely maintained, as the selective landscapes are under continual change through reciprocal selection on the Microorganisms 2021, 9, 240.

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Results

Conclusion