HOME

TheInfoList



OR:

Cecropins are
antimicrobial peptide Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for an ...
s. They were first isolated from the
hemolymph Hemolymph, or haemolymph, is a fluid, analogous to the blood in vertebrates, that circulates in the interior of the arthropod (invertebrate) body, remaining in direct contact with the animal's tissues. It is composed of a fluid plasma in which ...
of ''
Hyalophora cecropia ''Hyalophora cecropia'', the cecropia moth, is North America's largest native moth. It is a member of the family Saturniidae, or giant silk moths. Females have been documented with a wingspan of five to seven inches (160 mm) or more. These ...
'', whence the term cecropin was derived. Cecropins
lyse Lyse may refer to: * Lyse Abbey, a former Cistercian abbey in Norway * Lyse, an alternative name of Lysebotn, Norway * Lyse Energi, a Norwegian power company * Łyse, Masovian Voivodeship, a village in east-central Poland * Łyse, Podlaskie Voi ...
bacterial cell membranes; they also inhibit proline uptake and cause leaky membranes. Cecropins constitute a main part of the
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
of
insects Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of ...
. Cecropins are small proteins anywhere from 31 - 37 amino acids long and are active against both
gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bac ...
and
gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
. Cecropins isolated from insects other than ''
Hyalophora cecropia ''Hyalophora cecropia'', the cecropia moth, is North America's largest native moth. It is a member of the family Saturniidae, or giant silk moths. Females have been documented with a wingspan of five to seven inches (160 mm) or more. These ...
'' (Cecropia moth) have been given various names, such as bactericidin, lepidopterin, and
sarcotoxin Sarcotoxins are a group of antibacterial peptides present in the flesh fly belonging to the genus ''Sarcophaga ''Sarcophaga'' is a genus of true flies and the type genus of the flesh-fly family ( Sarcophagidae). The members of this cosmopolita ...
. All of these peptides are structurally related.


Members

Members include: ;Cecropin A: Peptide Sequence (KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK). Secondary structure includes two α helices. At low peptide to lipid ratios
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...
s are formed, at high peptide to lipid ratios pores are formed. ;Cecropin B: Peptide Sequence (KWKVFKKIEKMGRNIRNGIVKAGPAIAVLGEAKAL). Secondary structure includes two α helices. ;CECD: from
Aedes aegypti ''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its legs ...
(Yellowfever mosquito).cecropin family OPM
/ref> ;Papiliocin: from
Papilio xuthus ''Papilio xuthus'', the Asian swallowtail, Chinese yellow swallowtail or Xuthus swallowtail, is a yellow-colored, medium to large sized swallowtail butterfly found in northeast Asia, northern Myanmar, southern China, Taiwan, the Korean Peninsu ...
(a butterfly) ;Cecropin P1: Peptide Sequence (SWLSKTAKKLENSAKKRISEGIAIAIQGGPR). An antibacterial peptide from ''
Ascaris suum ''Ascaris suum'', also known as the large roundworm of pig, is a parasitic nematode that causes ascariasis in pigs. While roundworms in pigs and humans are today considered as two species (''A. suum'' and '' A. lumbricoides'') with different host ...
'', a parasitic nematode that resides in the pig intestine, also belongs to this family.


Derivatives

A derivative of Cecropin B is an anticancer polypeptide(L). Structure consists of mainly alpha helixes, determined by solution NMR. Protein molecular weight = 4203.4g/mol.; Some of the cecropins (e.g. cecropin A, and cecropin B) have anticancer properties and are called anticancer peptides (ACPs). Hybrid ACPs based on Cecropin A have been studied for anticancer properties.


Anticancer properties

Anticancer activities of cecropin B, cecropin P1, and Shiva-1 were first demonstrated with in vitro studies of mammalian leukemia and lymphoma cell lines, where cells were sensitive to peptide concentrations on the order of 10−6 M. Two multidrug-resistant breast and ovarian cancer cell lines also showed sensitivity to the peptides. Further, peptide anticancer activity is reported as being complete within one hour of treatment. In vivo studies of murine ascitic colon adenocarcinoma cells showed a similar trend, where mice treated with cecropin B exhibited increased survival time compared to untreated mice. Structural studies of cecropin B and its derivative cecropin B3 showed that anticancer activity arises from the ability of the antimicrobial peptides to form pores in stomach carcinoma cell membranes. Measuring electrical currents on cell surfaces showed that cecropin B, but not cecropin B3, induces outward currents indicative of pore formation. Further, cecropin B3 lacks an amphipathic group present in cecropin B, suggesting that this amphipathic group is necessary for cecropin B to insert into cell membranes and form pores. Cecropin B has strong activity on bacteria as well as cancer cells, while B3 has little effect on either. Notably, another derivative, cecropin B1, has two amphipathic regions and exhibits potent activity against human leukemia cell lines at concentrations that do not affect normal fibroblasts or red blood cells. Different cecropins act on different types of human cancer cells and show activity at concentrations that are not harmful to normal cells. For example, a recent study of Cecropins A and B demonstrated strongly cytotoxic activity against four bladder cancer cell lines, while benign murine and human fibroblasts were not susceptible to Cecropin A or B. Cecropins from many insect species have been shown to be active against a diverse range of human cancer cell lines. For example, Mdcec, a cecropin originating from the common housefly, has been shown to have an antiproliferative effect on human hepatocellular carcinoma cell line BEL-7402 without affecting normal liver cells. Flow cytometry and RT-PCR experiments revealed that treatment with Mdcec increased expression of pro-apoptotic genes such as caspase-3, leading to cancer cell death. These same genes did not show significant expression changes in healthy cells upon treatment with Mdcec. This suggests a degree of specificity which has promise for development of novel cancer therapies. Further supporting therapeutic efficacy, a study of cecropin A affirmed that cecropin A selectively lyses leukemia cells while exerting little effect on normal lymphocytes. In the same study, chemotherapy drugs cytarabine and 5-fluorouracil synergize with cecropin A in vitro to enhance cytotoxic effects on leukemia cells. This indicates potential for therapeutic application of antimicrobial peptides in cancer, where treatment with cecropins could lower the required dosage of chemotherapy drugs, reducing undesirable side effects. Major challenges to the use of cecropins as cancer therapeutics are delivery of the peptides to tumor cells. Repeated administration of peptides is necessary to maintain systemic levels of cecropins at sufficient concentrations for anti-cancer activity. This need for repeated administration complicates potential treatment plans. One proposed alternative suggests use of gene therapy to introduce cecropin genes into cancer cells. A study in which cecropin genes were expressed in a human bladder carcinoma cell line showed that tumor cells bearing cecropin genes have reduced tumorigenicity, up to complete loss of tumorigenicity in some cell clones. More recent studies have identified new cecropins, which may be prove useful in development of cancer therapeutics. For example, genome and transcriptome analyses of the
spruce budworm ''Choristoneura'' is a genus of moths in the family Tortricidae. Several species are serious pests of conifers, such as spruce and are known as spruce budworms. Species *'' Choristoneura adumbratanus'' (Walsingham, 1900) *'' Choristoneura afr ...
''
Choristoneura fumiferana ''Choristoneura fumiferana'', the eastern spruce budworm, is a species of moth of the family Tortricidae native to the eastern United States and Canada. The caterpillars feed on the needles of spruce and fir trees. Eastern spruce budworm popula ...
'' resulted in identification of novel cecropins which differ from previously characterized cecropins in that they are negatively charged, rather than positively charged. A BH3-like motif (amino acid sequence G- QR KQNR V QR is present in both anionic and cationic cecropins, and analysis suggests that this motif may interact with Bcl-2, a protein implicated in apoptosis. Further study of cecropin structure and anticancer properties may inform design of novel cancer therapeutics.


Antibiofilm properties

Cecropin A can destroy planktonic and sessile
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular p ...
-forming uropathogenic ''E. coli'' (UPEC) cells, either alone or when combined with the antibiotic
nalidixic acid Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics. In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that ...
, synergistically clearing infection in vivo (in the insect host ''
Galleria mellonella ''Galleria mellonella'', the greater wax moth or honeycomb moth, is a moth of the family Pyralidae. ''G. mellonella'' is found throughout the world. It is one of two species of wax moths, with the other being the lesser wax moth. ''G. mellonella ...
'') without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids.>


References


Further reading

* Hoskin 2008 (above) section 4.2


External links


Cecropins. OPM
{{Pore-forming toxins Antimicrobial peptides Insect immunity