PqsA mutation-mediated enhancement of phage-mediated combat against Pseudomonas aeruginosa

Front Cell Infect Microbiol. 2024 Feb 26:14:1296777. doi: 10.3389/fcimb.2024.1296777. eCollection 2024.

Abstract

Phage therapy is a potential approach in the biocontrol of foodborne pathogens. However, the emergence of phage resistance and the narrow host range of most phage isolates continue to limit the antimicrobial efficacy of phages. Here, we investigated the potential of the pqsA gene, encoding the anthranilate-CoA ligase enzyme, as an adjuvant for phage therapy. The knockout of the pqsA gene significantly enhanced the bactericidal effect of phages vB_Pae_QDWS and vB_Pae_S1 against Pseudomonas aeruginosa. Under phage infection pressure, the growth of the PaΔpqsA was significantly inhibited within 8 h compared to the wild-type PAO1. Furthermore, we found that altering phage adsorption is not how PaΔpqsA responds to phage infection. Although pqsA represents a promising target for enhancing phage killing, it may not be applicable to all phages, such as types vB_Pae_W3 and vB_Pae_TR. Our findings provide new material reserves for the future design of novel phage-based therapeutic strategies.

Keywords: P. aeruginosa; enhancement of phage therapy; phage; pqsA; resistance.

MeSH terms

  • Bacteriophages*
  • Humans
  • Mutation
  • Phage Therapy*
  • Pseudomonas Infections* / therapy
  • Pseudomonas Phages* / genetics
  • Pseudomonas aeruginosa / genetics

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of Shandong Province of China (ZR2022QC039), the National Natural Science Foundation of China (no. 32201982 and 32270152), and the Earmarked Fund for China Agriculture Research System (CARS-47).