Exploring the mechanisms by which camel lactoferrin can kill Salmonella enterica serovar typhimurium and Shigella sonnei

PeerJ. 2023 Jan 30:11:e14809. doi: 10.7717/peerj.14809. eCollection 2023.

Abstract

There is a continuously increasing pressure associated with the appearance of Salmonella enterica Serovar typhimurium (S. typhimurium) and Shigella sonnei (S. sonnei) that have developed pathogenic multiple antibiotic resistance and the cost of cure and control of these enterobacteriaceae infections increases annually. The current report for first time demonstrated the distinguished antimicrobial action of camel lactoferrin (cLf) obtained from the milk of different clans of camel in Saudi Arabia against S. typhimurium and S. sonnei. These cLf subtypes showed comparable antimicrobial potential when tested against the two bacterial strains but were superior to either bovine (bLf) or human lactoferrin (hLf). The synergism between lactoferrins and antibiotics concerning their antibacterial efficacies against the two bacterial strains was evident. Exploring mechanisms by which camel lactoferrin can kill S. typhimurium and S. sonnei revealed that cLf affects bacterial protein profile. Besides, it interacts with bacterial lipopolysaccharides (LPS) and numerous membrane proteins of S. typhimurium and S. sonnei, with each bacterial strain possessing distinctive binding membrane proteins for lactoferrin. Furthermore, as evidenced by electron microscopy analysis, cLf induces extracellular and intracellular morphological changes in the test bacterial strains when used alone or in combination treatment with antibiotics. Lactoferrin and antibiotics combination strongly disrupts the integrity of the bacterial cells and their membranes. Therefore, cLf can kill S. typhimurium and S. sonnei by four different mechanisms, such as iron chelation, affecting some bacterial proteins, binding to bacterial LPS and membrane proteins, and impairing the integrity of the bacterial cells and their membranes.

Keywords: Antibacterial; Camel milk; Lactoferrin; Salmonella typhimurium; Shigella sonnei.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents*
  • Camelus / metabolism
  • Cattle
  • Humans
  • Lactoferrin / pharmacology
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / metabolism
  • Salmonella typhimurium* / metabolism
  • Serogroup
  • Shigella sonnei / metabolism

Substances

  • Lactoferrin
  • Lipopolysaccharides
  • Anti-Infective Agents
  • Anti-Bacterial Agents
  • Membrane Proteins

Grants and funding

This work was supported by the King Abdulaziz City for Science and Technology General Directorate of Research Grants Programs, under grant no. LGP-35-84. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.