Evolution of Pseudomonas aeruginosa Virulence as a Result of Phage Predation

Abstract

The rapid increase in the emergence of antibiotic-resistant bacteria has attracted attention to bacteriophages for treating and preventing bacterial infections. Bacteriophages can drive the diversification of Pseudomonas aeruginosa, giving rise to phageresistant variants with different phenotypes from their ancestral hosts. In this study, we sought to investigate the effect of phage resistance on cytotoxicity of host populations toward cultured mammalian cells. The library of phage-resistant P. aeruginosa PAO1 variants used was developed previously via experimental evolution of an isogenic host population using phages PP7 and E79. Our results presented herein indicate that the phage-resistant variants developed in a heterogeneous phage environment exhibit a greater ability to impede metabolic action of cultured human keratinocytes and have a greater tendency to cause membrane damage even though they cannot invade the cells in large numbers. They also show a heightened resistance to phagocytosis by model murine macrophages. Furthermore, all isolates produced higher levels of at least one of the secreted virulence factors, namely, total proteases, elastase, phospholipase C, and hemolysins. Reverse transcription-quantitative PCR (RT-qPCR) revealed upregulation in the transcription of a number of genes associated with virulence of P. aeruginosa for the phage-resistant variants. The results of this study indicate a significant change in the in vitro virulence of P. aeruginosa following phage predation and highlight the need for caution in the selection and design of phages and phage cocktails for therapeutic use.

Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria

“…Oligonucleotide primers (Table 1) were designed using Primer3Plus (27) based on the published genome sequences of CFT073, HI4320, PAO1, and PA14. Moreover, the reported oligonucleotide primer sequences (28)(29)(30)(31)(32)(33)(34)(35)(36) used to amplify the gene of interest are listed in Table 1.…”

Long‐term effects of single and combined introductions of antibiotics and bacteriophages on populations of Pseudomonas aeruginosa

“…), and limited work has considered the effect of combining different concentrations of antibiotics or phages on bacterial virulence (Hosseinidoust et al. ). These are important questions, because it is not clear to what extent initially intense ecological interactions, longer‐term evolutionary effects, and/or their interactions influence outcomes.…”

Phages can constrain protist predation-driven attenuation of Pseudomonas aeruginosa virulence in multienemy communities

“…As with protist predation, phages can maintain bacterial virulence via production of public goods (Morgan et al, 2012), or by selecting for upregulation of bacterial virulence factors (Hosseinidoust et al, 2013). However, bacterial resistance to phages is also frequently associated with pleiotropic costs in terms of reduced growth rate (Lenski, 1988;Bohannan and Lenski, 1999;Bohannan et al, 2002;Buckling et al, 2006) or reduced colonization ability (Laanto et al, 2012) that can result in reductions in virulence in insect or fish hosts (Laanto et al, 2012).…”