The apicomplexan parasite Cryptosporidium parvum is an important cause of
diarrhea in humans and cattle, and it can persistently infect immunocompromised hosts. No consistently effective parasite-specific
pharmaceuticals or
immunotherapies for control of
cryptosporidiosis are presently available. The innate immune system represents the first line of host defense against a range of infectious agents, including parasitic protozoa. Several types of
antimicrobial peptides and
proteins, collectively referred to herein as
biocides, constitute a major effector component of this system. In the present study, we evaluated
lactoferrin,
lactoferrin hydrolysate, 5 cationic
peptides (
lactoferricin B,
cathelicidin LL37,
indolicidin, β-
defensin 1, β-
defensin 2),
lysozyme, and 2
phospholipases (
phospholipase A2, and
phosphatidylinositol-specific phospholipase C) for anti-cryptosporidial activity. The
biocides were evaluated either alone or in combination with 3E2, a
monoclonal antibody (MAb) against C. parvum that inhibits sporozoite attachment and invasion. Sporozoite viability and infectivity were used as indices of anti-cryptosporidial activity in vitro. All
biocides except
lactoferrin had a significant effect on sporozoite viability and infectivity.
Lactoferrin hydrolysate and each of the 5 cationic
peptides were highly parasiticidal and strongly reduced sporozoite infectivity. While each
phospholipase also had parasiticidal activity, it was significantly less than that of
lactoferrin hydrolysate and each of the cationic
peptides. However, each
phospholipase reduced sporozoite infectivity comparably to that observed with
lactoferrin hydrolysate and the cationic
peptides. Moreover, when 3 of the cationic
peptides (
cathelicidin LL37, β-
defensin 1, and β-
defensin 2) were individually combined with MAb 3E2, a significantly greater reduction of sporozoite infectivity was observed over that by 3E2 alone. In contrast, reduction of sporozoite infectivity by a combination of either
phospholipase with MAb 3E2 was no greater than that by 3E2 alone. These collective observations suggest that cationic
peptides and
phospholipases neutralize C. parvum by mechanisms that are predominantly either parasiticidal or non-parasiticidal, respectively.