Detoxification of Mycotoxins by Insects - American Chemical Society

Chapter

21

Detoxification of Mycotoxins by Insects

Downloaded by PENNSYLVANIA STATE UNIV on August 2, 2012 | http://pubs.acs.org Publication Date: September 22, 1992 | doi: 10.1021/bk-1992-0505.ch021

Patrick F. Dowd Mycotoxin Research Unit, National Center for Agricultural Utilization Research, U.S. Department of Agriculture, Agricultural Research Service, 1815 North University Street, Peoria, IL 61604

Resistance to aflatoxin B1 in Drosophila melanogaster is conferred by at least two chromosomes and cytoplasmic factors, and it is thought that unspecific monooxygenases may be involved. Resistance to α-amanitin in D. melanogaster is due to an altered target site, RNA polymerase II. Relative resistance to aflatoxin B and griseofulvin in Spodoptera frugiperda is due to lower rates of activation and higher rates of detoxificatian compared to Helicoverpa zea. Fungus-feeding larvae of Carpophilus hemipterus are able to hydrolyze a model trichothecene substrate at about 10-fold the rate of H. zea and S. frugiperda. 1

Mycotoxins are secondary metabolites produced by fungi t h a t are t o x i c t o animals, i n c l u d i n g humans. They represent j u s t a small p o r t i o n o f the many secondary metabolites produced by fungi ( 1 , 2 ) . Most mycotoxins are produced by molds i n the genera Aspergillus, Penicillium, and Fusarium. Some represent a t i v e s and t h e i r effects are l i s t e d i n Table I , and cxsrresponding structures are shown i n Figure 1. Unlike p l a n t secondary metabolites, the r e c o g n i t i o n t h a t fungal secondary metabolites such as mycotoxins can a c t as defensive substances has occurred only r e c e n t l y (3). Nevertheless, the e f f e c t s o f s e v e r a l mycotoxins on i n s e c t s have been studied t o some degree (see reviews 4 , 5 ) . Studies on i n s e c t s have been prompted by d e s i r e s t o examine the defensive c a p a b i l i t i e s o f mycotoxins, t o t e s t i n s e c t s as a l t e r n a t i v e bioassay i n d i c a t o r s , and t o search f o r new i n s e c t i c i d e s or novel b i o a c t i v e metabolites t h a t provide leads for new i n s e c t i c i d e s .

This chapter not subject to U.S. copyright Published 1992 American Chemical Society

In Molecular Mechanisms of Insecticide Resistance; Mullin, C., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

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O Figure 1. Representative myxxjtodns: a. a f l a t o x i n B b. ochratoxin A , c . g r i s e o f u l v i n , d . penitrem A , e. deoxynivalenol, f . diacetoxy-scirpenol, g . T-2 t o x i n , h . a-amanitin. lt


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Table I .

Representative Mycotoxins and T h e i r E f f e c t s

Aspergillus aflatoxins sterigmatocystin ochratoxin A

hepatotoxic, carcinogenic carcinogenic nephrotoxic, carcinogenic

Penicillium citrinin griseofulvin patulin rubratoxins penitrems p e n i c i l l i c acid

hepatotoxic carcinogenic, teratogenic t o x i c , carcinogenic hepatotoxic tremorgenic carcinogenic

Fusarium T-2 t o x i n deoxynivalenol diacetoxyscirpenol zearalenone

dermal n e c r o s i s , hemorrhagic emetic, nephrotoxic dermal n e c r o s i s , hemorrhagic estrogenic

Myootoxin Effects on Insects For the most p a r t , c a r c i n o g e n i c i t y i s not o f concern i n i n s e c t studies due t o the r a r i t y o f i n s e c t cancers. Thus, the reported e f f e c t s o f mycotoxins on i n s e c t s include acute t o x i c i t y , reduction i n growth r a t e s , morphological, h i s t o l o g i c a l and reproductive changes. The two most e x t e n s i v e l y studied groups o f mycotoxins are the a f l a t o x i n s and the trichothecenes. These cxxipounds presumably a c t on i n s e c t s i n a manner s i m i l a r t o the way they a c t on mammals, by b i n d i n g w i t h DNA (aflatoxins) o r by i n h i b i t i n g p r o t e i n synthesis (both). Insects fed these ocnpounds may d i e , have reduced growth r a t e s , o r reduced fecundity. Af l a t o x i n i s reported t o induce recessive l e t h a l mutants i n Drosophila melanogaster (6). The tremorgenic mycotoxins i n t e r a c t w i t h the i n s e c t nervous system presumably as they do i n vertebrates, by a f f e c t i n g 7-aminob u t y r i c a c i d (GABA), glutamic, o r other tramsmitters/receptor systems (5). Those t h a t a f f e c t nitrogen r e g u l a t i o n and manifest t h e i r e f f e c t s on the mammalian kidney can a l s o a f f e c t the corresponding structures i n i n s e c t s , the Malpighian tubules (7). I n f a c t , v i r t u a l l y a l l mycotoxins have some e f f e c t on i n s e c t s a t n a t u r a l l y occurring concentrations ( t y p i c a l l y 25 ppm) (5). Thus, i t i s easy t o understand why mycotoxins are considered as defenses against i n s e c t s , as w e l l as mammals. The i m p l i c a t i o n s o f t h i s concept are t h a t a l l o f the r e a c t i o n s and i n t e r r e l a t i o n s h i p s known f o r i n s e c t s and p l a n t secondary metabolites can a l s o be a p p l i e d t o i n s e c t s and mycotoxins.


21. DOWD


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Insect "Resistance" to Myootoodns Insect resistance t o myrataxins m y have evolved through continuous exposure and/or targeted feeding. Resistance t o p l a n t secondary metabolites and s y n t h e t i c i n s e c t i c i d e s i s sometimes thought t o r e s u l t from predisposed adaptations t o (for example) p l a n t secondary metabolites t h a t have p a r t i c u l a r f u n c t i o n a l groups i n common. The same s i t u a t i o n i s relevant f o r z o o t o x i n s . For example, d e t o x i f y i n g enzyme systems t h a t evolved i n i n s e c t s t o d e a l k y l a t e p l a n t a l l e l o c h e m i c a l s may be capable o f d e a l k y l a t i n g mycotoxins. P o s s i b l y , i n s e c t resistance t o mycotoxins i s a n c e s t r a l t o r e s i s t a n c e t o p l a n t a l l e l o c h e m i c a l s . Based on speculated times o f o r i g i n , i n s e c t s (8) and fungi (9) have been i n t e r a c t i n g f o r nearly 400 m i l l i o n years. This i s approximately 275 m i l l i o n years longer than the p e r i o d t h a t i n s e c t s have been i n t e r a c t i n g w i t h flowering p l a n t s (based on a time o f o r i g i n 125 m i l l i o n years ago - 10). P a r a l l e l evolutionary development o f r e s i s t a n c e t o mycotoxins and p l a n t a l l e l o c h e m i c a l s by i n s e c t s i s a l s o a p o s s i b i l i t y . I n t e r e s t i n g l y , one o f the "oldest" i n s e c t groups, the cockroaches, i s a l s o one o f the most r e s i s t a n t t o af l a t o x i n s (11). The af l a t o x i n s themselves may represent the present day b i o s y n t h e t i c endpoint f o r a progression o f precursors t h a t show a decreasing t o x i c i t y t o i n s e c t s the further they are removed from af l a t o x i n s (12). Insects w i t h s i m i l a r host ranges have d i f f e r e n t s e n s i t i v i t i e s t o mycotoxins even though they would not be expected t o have adapted t o mycotoxins due t o targeted feeding. One example i s Spodoptera frugiperda and Heliooverpa zea, both o f which may feed on corn or other p l a n t s o c c a s i o n a l l y contaminated w i t h mycotoxins. Based on s u b l e t h a l e f f e c t s a t 0.25 ppm (13), H. zea i s about 10-fold more s e n s i t i v e t o a f l a t o x i n B than S. frugiperda. I n contrast, S. frugiperda i s more s e n s i t i v e than H. zea t o the tremorgen roseotoxin B a t 25 ppn i n d i e t s (100% v s . 38% m o r t a l i t y , r e s p e c t i v e l y ) . The converse i s t r u e f o r the tremorgen penitrem A (20% v s . 80% reduction i n growth r a t e s , r e s p e c t i v e l y , a t 0.25 ppm i n d i e t s ) (14). G r i s e o f u l v i n , a myootoxin t h a t i s a l s o used p h a r m a c e u t i c a l ^ t o t r e a t fungal s k i n i n f e c t i o n s , i s more t o x i c t o H. zea than S. frugiperda (Dowd, P . F . , unpublished data see following d i s c u s s i o n ) . On the other hand, most trichothecenes are o f s i m i l a r t o x i c i t y t o both i n s e c t s (5,15-17). There i s a l s o v a r i a b i l i t y i n s u s c e p t i b i l i t y o f d i f f e r e n t s t r a i n s o f Drosophila melancgaster t o a f l a t o x i n B ^ A t 400 ppb, a l l o f the Crimea s t r a i n d i e d , 24% o f the Swedish-C s t r a i n reached adulthood and approximately 70% o f the Hikone-R, Lausanne-S, and Oregon-R s t r a i n s reached adulthood (18). These differences i n s u s c e p t i b i l i t y suggest t h a t some s o r t o f r e s i s t a n c e mechanism(s) are present. There are other examples where continuous exposure, has apparently produced resistance t o mycotoxins i n i n s e c t s . Stored product beetles appear r e l a t i v e l y r e s i s t a n t t o ochratoxin A and TV-2 t o x i n (19) compared t o stored product c a t e r p i l l a r s (20). P o s s i b l y the beetles are l e s s mobile than the moths and have experienced greater s e l e c t i o n pressure when stored m a t e r i a l s have become contaminated w i t h myootoxin-prxxJucirig fungi. 1



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There are a l s o cases where targeted feeding on inycotoxiri-

Detoxification of Mycotoxins by Insects - American Chemical Society

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