Higher phage virulence accelerates the evolution of host resistance

Abstract

Pathogens vary strikingly in their virulence and the selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and, at present, mainly based on observations and theoretical predictions with few experimental tests. Increased virulence can increase selection for host resistance evolution if the benefits of avoiding infection outweigh resistance costs. To test this, we experimentally evolved the bacterium Vibrio alginolyticus in the presence of two variants of a filamentous phage that differ in their virulence. The bacterial host exhibited two alternative defence strategies: (1) super infection exclusion (SIE), whereby phage-infected cells were immune to subsequent infection at the cost of reduced growth, and (2) surface receptor mutations (SRM), providing resistance to infection by preventing phage attachment. While SIE emerged rapidly against both phages, SRM evolved faster against the high- than the low-virulence phage. Using a mathematical model of our system, we show that increasing virulence strengthens selection for SRM owing to the higher costs of infection suffered by SIE immune hosts. Thus, by accelerating the evolution of host resistance, more virulent phages caused shorter epidemics.

Sub-Optimal Environmental Conditions Prolong Phage Epidemics in Bacterial Populations

“…In a previous study (Wendling et al, 2022) we found that in the presence of Vibrio phage VALGΦ8 the bacterium V. alginolyticus K01M1 evolved phage resistance by modifying the viral binding site. These mutants rapidly replaced phage-carriers, which were resistant due to super infection exclusion (SIE)-immunity.…”

“…In a previous study (Wendling et al, 2022), we found two alternative defence strategies conferring resistance against the co-evolving filamentous Vibrio phage VALGΦ8: (1) superinfection exclusion (SIE) resulting from the presence of the co-evolving phage in the bacteria cell or (2) surface receptor mutations (SRM) in the MSHA type IV pilus preventing phage attachment. To quantify the frequency of co-evolving strains that acquired resistance by superinfection exclusion, we used colony PCR with a primer pair that specifically targets a unique region in the co-evolving Vibrio phage VALGΦ8 following a previous protocol (Wendling et al, 2022). PCR-bands at a length of 1.2 kbp were interpreted as presence of VALGΦ8 in the bacterial cell indicating SIE.…”

“…While the evolution of resistance is a common strategy for hosts to counteract parasitism, the costs of resistance often vary, making it difficult to predict when and how resistance evolves. Theory predicts and experiments confirmed that in the absence of significant resistance costs, resistance rapidly emerges and reaches fixation (Agrawal & Lively, 2002; Buckling & Rainey, 2002; Wendling et al, 2022). With increasing costs of resistance however, intermediate resistance levels or co-existence of non-resistant and resistant subpopulations may appear (Boots & Haraguchi, 1999).…”

“…To do so, we performed a selection experiment at three different salinity levels using the marine bacterium V. alginolyticus strain K01M1 (Chibani, Roth, Liesegang, & Wendling, 2020) and the filamentous Vibrio phage VALGΦ8 (Chibani, Hertel, Hoppert, Liesegang, & Wendling, 2020). Filamentous phages (family Inoviridae ), i.e., long, thin proteinaceous filaments which contain a circular single-stranded DNA genome, are ideal model systems to study virulence (Messenger, Molineux, & Bull, 1999; Turner, Cooper, & Lenski, 1998) and resistance evolution (Wendling et al, 2022). Filamentous phages often establish chronic infections whereby virions are continuously released without lysis.…”

“…Filamentous phages often establish chronic infections whereby virions are continuously released without lysis. This costly feature of filamentous phages often reduces bacterial growth rates (Wendling et al, 2022), because bacteria pay the metabolic costs resulting from phage replication and through phage-encoded proteins inserted into the bacterial membrane (Mai-Prochnow et al, 2015).…”