A new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in Anopheles mosquitoes

PLoS One. 2011 May 6;6(5):e19649. doi: 10.1371/journal.pone.0019649.

Abstract

Background: Plasmodium requires an obligatory life stage in its mosquito host. The parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. Lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.

Methodology/principal findings: A mosquito lysozyme was identified as a protective agonist for Plasmodium. Immunohistochemical analyses demonstrated that Anopheles gambiae lysozyme c-1 binds to oocysts of Plasmodium berghei and Plasmodium falciparum at 2 and 5 days after infection. Similar results were observed with Anopheles stephensi and P. falciparum, suggesting wide occurrence of this phenomenon across parasite and vector species. Lysozyme c-1 did not bind to cultured ookinetes nor did recombinant lysozyme c-1 affect ookinete viability. dsRNA-mediated silencing of LYSC-1 in Anopheles gambiae significantly reduced the intensity and the prevalence of Plasmodium berghei infection. We conclude that this host antibacterial protein directly interacts with and facilitates development of Plasmodium oocysts within the mosquito.

Conclusions/significance: This work identifies mosquito lysozyme c-1 as a positive mediator of Plasmodium development as its reduction reduces parasite load in the mosquito host. These findings improve our understanding of parasite development and provide a novel target to interrupt parasite transmission to human hosts.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anopheles / drug effects
  • Anopheles / enzymology*
  • Anopheles / parasitology*
  • Anti-Infective Agents / metabolism*
  • Antibodies / pharmacology
  • Bacteria / drug effects
  • Bacteria / growth & development
  • Colony Count, Microbial
  • Digestive System / drug effects
  • Digestive System / enzymology
  • Gene Knockdown Techniques
  • Gene Silencing / drug effects
  • Humans
  • Malaria / parasitology*
  • Molecular Sequence Data
  • Muramidase / chemistry
  • Muramidase / metabolism*
  • Oocysts / cytology
  • Oocysts / drug effects
  • Oocysts / metabolism
  • Parasites / cytology
  • Parasites / drug effects
  • Parasites / physiology*
  • Pigmentation / drug effects
  • Plasmodium berghei / cytology
  • Plasmodium berghei / drug effects
  • Plasmodium berghei / physiology
  • Plasmodium falciparum / cytology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / physiology

Substances

  • Anti-Infective Agents
  • Antibodies
  • Muramidase