NATURE |VOLUME 5 | MAY 2007

OPINION

Can fungal biopesticides controlMalaria?

Matthew B. Thomas and Andrew F. ReadAhmad Ali(c.no:42)

3rd year(semester 6th)

Concept of the perspective

• To realize the lateral thinking of biologist technologists and development agencies.

• To raise the prospect of using insect fungal pathogens for the control of vector-borne diseases.

• possible to produce a cheap, safe and green tool for the control of vector-borne diseases.

Background of the prespective• Biocontrol: (grass hopper control)• in Africa, the international donor community supported

a research programme named LUBILOSA (Lutte BiologiqueContre les Locustes et les Sautereaux).

• identified a virulent strain of the entomopathogenic fungus Metarhizium anisopliae var. acridum

• Cause infection in conditions ofvery low relative humidity .

Green Muscle and Green guard(a registered trademark)

Biopesticides for the control oflocusts and grasshoppers in Africa.

• A virulent strain of the fungal entomopathogen Metarhizium anisopliae var acridum was isolated from infected grasshoppers collected from the field.

• Spores are located on the inter-segmental membranes.

• Simple techniques have been developed for in vitro mass production.

• spores are grown in bowls using partcooked rice as a solid substrate.

cont’d• Fungal spores are then harvested from the

rice and formulated in oil for ultra-low-volume application using hand-held vehicle or aerial-mounted sprayers.

• Infected locusts and grasshoppers typically die in 7–25 days.

• the speed of kill is strongly influenced by environmental temperature and insect thermal behaviour in this system.

strategies forovercoming host defense responses

• Development of cryptic growth forms that are effectively masked from the insect defence responses.

• production of immunomodulating substancesthat suppress the host defense system.

How it work???

The in vivo development cycle of entomopathogenic fungi

sequential steps ………………

• First, conidia (spores) adhere to the host cuticle

• then the conidia germinate(penetration structure) are produced.

• The cuticle is penetrated by a combinationof mechanical pressure and the action of cuticle

degrading enzymes.• cuticle degradation• successful infection

Approach behind these studies…. Proof of concept for malaria control

• Several studies have investigated the use ofmicrobial biocontrol to kill mosquitoes.

• Typically, virulent pathogens have been isolated, with the aim of developing biopesticides to kill mosquito larvae.

Common approach……..• The common approach behind these studies is

to infect insects by exposure to oil-formulated fungal spores that have been applied to surfaces on which adult mosquitoes rest after blood meals.

a small-scale study in Tanzania confirmed the feasibility of infecting mosquitoes

with virulent fungi under field conditions in Africa.

Study was based on experimental formulation

• Low dose of an experimental formulationapplied over a small surface area.• The study used fungus-treated black cloths that were pinned to the ceilings

of dwellings.

• These cloths were repeatedly treated with spores at relatively little cost or inconvenience.

• These studies highlight that 34% of mosquitoes collected from targeted village houses were infected with fungi. Simple

epidemiological models predict that even this relatively low level of infection would result in a 75% reduction in entomological inoculation rate at this field site

Cont’d

Rodent model

Why reduction???Fungal infection reduces malaria transmission

by mosquitoes.• Female mosquitoes contact fungal spores

from treated surfaces as they rest to digest a blood meal.

• As the fungal infection progresses, mosquitoes die.

• In the correct conditions, a mat of fungal spores is deposited on the outside of the cadaver.

Contd’s• Infection with the entomopathogenic fungus

Beauvoir bassiana• dramatically reduces survival of Anopheles

mosquitoes by day 14 (the time following an infectious blood feed at which an individual mosquito becomes able to transmit malaria).

• In addition, there is an interaction with malaria parasites (Plasmodium chabaudi) whereby daily mortality rates accelerate from day 11 in those mosquitoes carrying both fungus and malaria.

Contd’s

• Mosquitoes infected with the fungus show a significant decline in their propensity to blood feed as the disease progresses.

• Survivorship or development of the malaria parasite inside the mosquito is affected such that, even if mosquitoes survive, there is less chance that they will contain infectious sporozoites in their mouthparts.

Disease concern things……….Disease pathology and biopesticides:• A crucial factor for the successful transmissionof malaria is approximately 2-week parasite

incubation period.• Even small reductions in adult mosquitolongevity after an infective blood meal canhave a large effect on the dynamics of themalaria parasite.• it is not necessary to rapidly kill the mosquito

with a virulent pathogen.

• But to overlooks their potential to influenceinsect behaviour and fitness in subtle waysthat could also negatively affect malariatransmission without necessarily reducingvector density.• Locusts that are infected with fungi develop alterations

in several characteristics before death. such as feeding behaviour,fat-body accumulation, development rate,fecundity, mobility and predator-escaperesponses

Cont’d

• there is evidence that fungal pathogens can affect not only the mosquito, but also the survivorship of the malaria parasite within the mosquito.

• The mechanisms that underlie this anti-malariaeffect are unknown but might include alterations in host nutritional balance, which lead to resource

competition, upregulation of immune responses, or production of secondary metabolites in the haemolymph.

• The deleterious effects of sub-lethal pathogens on the capacity of insects to function as vectors of disease have been virtually ignored.

Cont’d

• Exploiting the sub-lethal effects of pathogenscould present new opportunities for thedevelopment of biopesticides.

Evolution of resistance:…………?????

the main effect of a fungal isolate was to reduce the fitness of malaria-infected mosquitoes (rather than all mosquitoes)

Cont’d

• this should reduce selectionpressure for fungal resistance across theentire mosquito population, and might evenselect for increased malaria refractoriness.• If there are such specific resistance

mechanisms. It means that fungi resistance would be related to ‘metabolic’ or ‘knockdown’ resistance mechanism.