Phase and antigenic variation govern competition dynamics through positioning in bacterial colonies

Robert Zöllner,Enno R Oldewurtel,Berenike Maier,Nadzeya Kouzel

doi:10.1038/s41598-017-12472-7

Abstract

Cellular positioning towards the surface of bacterial colonies and biofilms can enhance dispersal, provide a selective advantage due to increased nutrient and space availability, or shield interior cells from external stresses. Little is known about the molecular mechanisms that govern bacterial positioning. Using the type IV pilus (T4P) of Neisseria gonorrhoeae, we tested the hypothesis that the processes of phase and antigenic variation govern positioning and thus enhance bacterial fitness in expanding gonococcal colonies. By independently tuning growth rate and T4P-mediated interaction forces, we show that the loss of T4P and the subsequent segregation to the front confers a strong selective advantage. Sequencing of the major pilin gene of the spatially segregated sub-populations and an investigation of the spatio-temporal population dynamics was carried out. Our findings indicate that pilin phase and antigenic variation generate a standing variation of pilin sequences within the inoculation zone, while variants associated with a non-piliated phenotype segregate to the front of the growing colony. We conclude that tuning of attractive forces by phase and antigenic variation is a powerful mechanism for governing the dynamics of bacterial colonies.

Highlights

The contributions of genetic heterogeneity to the pathology, host persistence, transmission, and spread of bacterial pathogens is an expanding area of research relevant to a diverse range of species[1,2,3,4]
We have previously found that differential interaction forces between bacteria cause cellular sorting[12]
We showed that pilin phase variation and pilin antigenic variation are important for the population dynamics in gonococcal colonies

Summary

Introduction

The contributions of genetic heterogeneity to the pathology, host persistence, transmission, and spread of bacterial pathogens is an expanding area of research relevant to a diverse range of species[1,2,3,4]. In the case of the human pathogen Neisseria gonorrhoeae the major surface structures are extracellular polymers named type IV pili (T4P) This polymer consists of the major pilin subunit PilE and multiple minor pilins and mediates cell-cell interaction[11]. A high degree of variation in T4P could be observed during experimental human infections with gonorrhea with multiple pilE variants being present at each point of time These showed dynamic sequence variations, that likely occurred via recombination with silent copies[16,17]. It is tempting to speculate that phase and antigenic variation in surface-related genes generate genotypic heterogeneity that enables bacteria to influence their position within biofilms. Pilin variants with lowest interaction forces are selected for by being positioned to the front of the expanding colony

Methods

Results

Discussion

Conclusion