In vivo competition and horizontal gene transfer among distinct Staphylococcus aureus lineages as major drivers for adaptational changes during long-term persistence in humans

Lars Langhanki,Barbara C Kahl,Janina Treffon,Francesco Catania,Petya Berger,Alexander Mellmann

doi:10.1186/s12866-018-1308-3

Lars Langhanki, Barbara C Kahl + Show 4 more

Open Access

https://doi.org/10.1186/s12866-018-1308-3

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Abstract

BackgroundThe airways of the majority of adolescent cystic fibrosis (CF) patients are persistently colonized or infected by Staphylococcus aureus. Using whole genome sequencing, we studied the evolutionary traits within a S. aureus population in the airways of a CF patient hypothesizing that horizontal gene transfer (HGT) and inter-bacterial interaction play a major role in adaptation during long-term persistence.ResultsWhole genome sequencing of 21 S. aureus isolates spanning 13 years resulted in seven lineages defined by the spa types t012, t021, t331, t338, t364, t056, and t2351. Of these, the successfully persisting lineages t012 and t021 were closely related suggesting the evolution of t021 from t012, which was further corroborated by a nearly identical, syntenic set of mobile genetic elements. During transformation from t012 to t021, an increase of genomic changes including HGT from other S. aureus lineages was detected.ConclusionsIn summary, our in vivo data enabled us to conceptualize an evolutionary model showing the impact of HGT and inter-bacterial interaction on bacterial long-term adaptation to the human host during CF.

Highlights

The airways of the majority of adolescent cystic fibrosis (CF) patients are persistently colonized or infected by Staphylococcus aureus
Patients suffering from this disease, which is caused by deleterious mutations affecting the CF transmembrane conductance regulator (CFTR) [5, 6], show, among other symptoms, an impaired mucociliary clearance in the airways brought about by the thickening of the mucus fluids on epithelial cells [7]
Spa typing was first described as a highly discriminatory typing method based on the repeat pattern of the polymorphic region of spa [31, 32]; later a phylogenetic signal was attributed to the spa gene, which is highly concordant to multilocus sequence typing (MLST) and provides a higher level of discrimination than MLST by grouping strains of the same MLST sequence type (ST) into different spa types [33, 34]

Summary

Introduction

The airways of the majority of adolescent cystic fibrosis (CF) patients are persistently colonized or infected by Staphylococcus aureus. As a model system for the in vivo evolution and adaptation mechanisms of S. aureus during long-term persistence in the human host, we studied chronic airway infection in a cystic fibrosis (CF) patient Patients suffering from this disease, which is caused by deleterious mutations affecting the CF transmembrane conductance regulator (CFTR) [5, 6], show, among other symptoms, an impaired mucociliary clearance in the airways brought about by the thickening of the mucus fluids on epithelial cells [7]. It has been proposed by Freedman et al that dysfunction of the acinar tissue in CF may be due to an imbalance in the utilization of free fatty acids in the phospholipids of CF patients [8]. These changes cause recurrent and chronic bacterial infections, with S. aureus being especially one of the first pathogens

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