Roles of qseC mutation in bacterial resistance against anti-lipopolysaccharide factor isoform 3 (ALFPm3)

PLoS One. 2023 Jun 2;18(6):e0286764. doi: 10.1371/journal.pone.0286764. eCollection 2023.


Propelled by global climate changes, the shrimp industry has been facing tremendous losses in production due to various disease outbreaks, particularly early mortality syndrome (EMS), a disease caused by Vibrio parahaemolyticus AHPND. Not only is the use of antibiotics as EMS control agents not yet been proven successful, but the overuse and misuse of antibiotics could also worsen one of the most challenging global health issues-antimicrobial resistance. To circumvent antibiotic usage, anti-lipopolysaccharide factor isoform 3 (ALFPm3), an antimicrobial peptide (AMP) derived from the shrimp innate immune system, was proposed as an antibiotic alternative for EMS control. However, prolonged use of AMPs could also lead to bacterial cross resistance with life-saving antibiotics used in human diseases. Here, we showed that ALFPm3-resistant strains of E. coli could be induced in vitro. Genome analysis of the resistant mutants revealed multiple mutations, with the most interesting being a qseC(L299R). A study of antibiotic susceptibility profile showed that the resistant strains harboring the qseC(L299R) not only exhibited higher degree of resistance towards polymyxin antibiotics, but also produced higher biofilm under ALFPm3 stress. Lastly, a single cell death analysis revealed that, at early-log phase when biofilm is scarce, the resistant strains were less affected by ALFPm3 treatment, suggesting additional mechanisms by which qseC orchestrates to protect the bacteria from ALFPm3. Altogether, this study uncovers involvement of qseC mutation in mechanism of resistance of the bacteria against ALFPm3 paving a way for future studies on sustainable use of ALFPm3 as an EMS control agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / metabolism
  • Drug Resistance, Bacterial* / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Humans
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Protein Isoforms / genetics


  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Lipopolysaccharides
  • Protein Isoforms
  • QseC protein, E coli

Grants and funding

This research project is supported by Agricultural Research Development Agency (ARDA) (ID: CRP6105021050) and the Japan Science and Technology Agency (JST)/Japan International Cooperation Agency (JICA), Science and Technology Research Partnership for Sustainable Development, SATREPS JPMJSA1806 (K.S., P.N.). This research project is also supported by National Research Council of Thailand (NRCT) and Mahidol University: N42A650368 and Mahidol University under the New Discovery and Frontier Research Grant (P.N.). C.P. is supported by the National Science and Technology Development Agency (NSTDA) under the Junior Science Talent Project (JSTP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.