AUTHOR=Li Gang , Shen Mengyu , Yang Yuhui , Le Shuai , Li Ming , Wang Jing , Zhao Yan , Tan Yinling , Hu Fuquan , Lu Shuguang 

TITLE=Adaptation of Pseudomonas aeruginosa to Phage PaP1 Predation via O-Antigen Polymerase Mutation

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01170

DOI=10.3389/fmicb.2018.01170

ISSN=1664-302X

ABSTRACT=<p>Adaptation of bacteria to phage predation poses a major obstacle for phage therapy. Bacteria adopt multiple mechanisms, such as inhibition of phage adsorption and CRISPR/Cas systems, to resist phage infection. Here, a phage-resistant mutant of <italic>Pseudomonas aeruginosa</italic> strain PA1 under the infection of lytic phage PaP1 was selected for further study. The PaP1-resistant variant, termed PA1RG, showed decreased adsorption to PaP1 and was devoid of long chain <italic>O</italic>-antigen on its cell envelope. Whole genome sequencing and comparative analysis revealed a single nucleotide mutation in the gene PA1S_08510, which encodes the <italic>O</italic>-antigen polymerase Wzy that is involved in lipopolysaccharide (LPS) biosynthesis. PA1_Wzy was classified into the O6 serotype based on sequence homology analysis and adopts a transmembrane topology similar to that seem with <italic>P. aeruginosa</italic> strain PAO1. Complementation of gene <italic>wzy in trans</italic> enabled the mutant PA1RG to produce the normal LPS pattern with long chain <italic>O</italic>-antigen and restored the susceptibility of PA1RG to phage PaP1 infection. While <italic>wzy</italic> mutation did not affect bacterial growth, mutant PA1RG exhibited decreased biofilm production, suggesting a fitness cost of PA1 associated with resistance of phage PaP1 predation. This study uncovered the mechanism responsible for PA1RG resistance to phage PaP1 via <italic>wzy</italic> mutation and revealed the role of phages in regulating bacterial behavior.</p>