47:, so that they can be expressed in the vector. The final step in the strategy is to introduce these transgenic symbionts into vector populations in the wild. One use of this technique is to prevent mortality for humans from insect-borne diseases. Preventive methods and current controls against vector-borne diseases depend on insecticides, even though some mosquito breeds may be resistant to them. There are other ways to fully eliminate them. “Paratransgenesis focuses on utilizing genetically modified insect symbionts to express molecules within the vector that are deleterious to pathogens they transmit.” The acidic bacteria Asaia symbionts are beneficial in the normal development of mosquito larvae; however, it is unknown what Asais symbionts do to adult mosquitoes.
243:
most useful way to eliminate them is to use insecticides, some mosquito species are resistant to insecticide. In order to combat insecticide-resistant mosquitos, there are genetically engineered plasmodium that has been created to help destroy the mosquito gut. Another study “Using infection to fight infection: paratransgenesis fungi can block malaria transmission in mosquitoes” demonstrates anti-malaria effector genes that were injected into entomopathogenic fungus, Metarhizium anisopliae. Next, the fungus was injected into non-infected mosquitoes and expressed in the hemolymph. The interesting thing about this is when other molecules were coexpressed, the salivary glands expressed
Malaria levels up to 98%.
144:“Paratransgenesis is the genetically modified symbiotic organisms that block pathogen development or transmission by vectors using expressing molecules”. Figure 2 shows An. gambiae and Ae. aegypti symbiotic viruses using bacteria symbionts blood-sucking, tsetse flies and mosquitoes. Symbionts expressing molecules targeting pathogen development can have transmission in endemic regions. As with transgenesis, The spread of transformed symbionts benefits from the availability of a gene drive system to replace non-transformed symbionts present in natural vector populations is also seen in transgenesis. Paratransgenesis reduces African trypanosomes transmission by tsetse flies. It has transformed
234:
efforts to use paratransgenesis to prevent the spread of this disease. The strategy is to alter the microbe then reinsert it into the insect that has been genetically modified to alter pathogens. The article “Paratransgenic
Control of Vector Borne Diseases'' discusses the approach to understanding these diseases. Human African Trypanosomiasis (sleeping sickness) is an illness that affects many individuals in sub-Saharan Africa. In the last decade the numbers have come close to an elimination. This illness is passed by flies and the past few efforts on controlling this disease is less than 10,000 cases per year.
214:-infected insects in a population.” This effect will cause other transitional controlled transformed symbionts to spread within an insect population which expands the frequency. These insects include: Ae. aegypti, Aedes albopictus, and Culex quinquefasciatus. Densovirus is an example of how the spread is transformed through symbionts, occurring in the natural populations of mosquitoes.
133:
plasmids as it replicates in mosquitoes and in culture, reverting to wild type and that horizontal transfer of the plasmid from
Serratia AS1 to other bacteria is difficult to detect.” This means the initial field trials can be used in the reversible system besides the released recombinant bacteria expressing antiplasmodial compounds from a plasmid revert to wild type at a certain rate.
222:
over younger ones and this also implies evolution-proof of mosquitocidal biocontrols agents. Time already exists for a selective pressure on pathogen development in
Plasmodium-infected mosquitoes for Anopheles (marsh mosquitos) from 20% to 40% per gonotrophic cycle resulting in a shortening of the parasite life cycle within the vector.
116:
to see if maintaining the microbiome in the insect model’s guts would work to keep the bees and the entire colony healthy. There has been a major decrease in honey bee populations and colonies in recent years. By using paratransgenesis, scientists and beekeepers hope to increase the population of honey bees.
221:
strain reduces the mosquito lifespan for pathogen development inside the mosquito (known as the extrinsic incubation period or EIP). Elimination of the disease vectors is hard to treat due to reduced vector lifespan for its own growth from a shorter growth time. This means it targets older mosquitoes
242:
There are many diseases in which paratransgenesis can occur, with the most common being malaria. The paper “Evaluating the usefulness of paratransgenesis for malaria control,” describes the global problem of malaria, a cause of significant health issues. It is carried by mosquitoes and although the
195:
A future direction on vector paratransgenesis is within the natural insect populations and it has not been determined if transformed symbionts can replace non-transformed symbionts. There are no effects on insect hosts and are capable of being transmitted vertically (via trans-ovarian transmission)
115:
Another example is in honey bees. A study done in 2012 found that using lactic acid bacteria could improve or help with honey bee’s health and digestion. This is a different use of paratransgenesis and was suggested as the
Lactobacillus was an easy target for paratransgenesis. The scientists wanted
132:
Experiments have shown that the spread through mosquito populations is resistant to parasites engineered through symbiotic bacterium
Serratia AS1. Major concerns of regulators for the release of such engineered bacteria into the field shows there were zero options for “recall”. “Serratia AS1 loses
233:
Vector-borne diseases are common; therefore working to understand how these diseases are transmitted can lead to better prevention of or treatment for these illnesses. Vector borne diseases such as malaria are passed from mosquitoes to humans. Trypanosoma Cruz causes Chagas disease, and there are
107:
Although the use of paratransgenesis can serve many different purposes, one of the main purposes is “breaking the disease cycle”. This study focuses on the experiments with tsetse flies and trypanosomes, which cause sleeping sickness in
Subsaharan Africa. The tsetse fly’s transmission biology was
111:
Another disease caused by the transmission of mosquitoes to humans is malaria. This has been an ongoing health issue as there is not an effective vaccine and malaria is deadly. “The development of innovative control measures is an imperative to reduce malaria transmission.” In this study, it was
178:, which all have transmitted vertically via the female milk glands. Vertical transmission has GFP-transformed (recSodalis) that was detected in 9 out of 12 F1 offspring and eight out of 12 F2 descendents, which has transformed symbiont to be spread across tsetse populations. This resulted in
108:
studied to learn how it transmits the disease. This was done inn order to find the best way to use paratransgenesis, which could help solve transmission. In this case, paratransgenesis was used to create trypanocides which stop the transmission of trypanosomes in the tsetse fly vector.
225:“One approach is to reduce vector competence (linear parameter), and vector survivorship (exponential parameter). Both effects together should reduce vectorial capacity and disease burden in endemic areas and prevent transmission.”
889:
Ward TW, Jenkins MS, Afanasiev BN, Edwards M, Duda BA, Suchman E, et al. (October 2001). "Aedes aegypti transducing densovirus pathogenesis and expression in Aedes aegypti and
Anopheles gambiae larvae".
112:
found that when using paratransgenesis of Asaia (gfp) in these mosquitoes, there was a lower chance of the disease. They are using anti-pathogen effector molecules.
526:"Expression and extracellular release of a functional anti-trypanosome Nanobody® in Sodalis glossinidius, a bacterial symbiont of the tsetse fly"
137:
1298:"A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control"
942:
Cheng Q, Aksoy S (February 1999). "Tissue tropism, transmission and expression of foreign genes in vivo in midgut symbionts of tsetse flies".
500:
210:-uninfected females will not breed with infected males, which reduces the frequency of uninfected individuals and increases the frequency of
125:
192:
transforming with GFP, the recSodalis obtained colonized septic non-native tsetse host species at a density similar to native colonization.
1041:"Interspecific transfer of bacterial endosymbionts between tsetse fly species: infection establishment and effect on host fitness"
1144:
McMeniman CJ, Lane RV, Cass BN, Fong AW, Sidhu M, Wang YF, O'Neill SL (January 2009). "Stable introduction of a life-shortening
688:"Expression of a mutated phospholipase A2 in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development"
1559:
206:
are intracellular transitional bacteria that control the reproduction of insects via cytoplasmic incompatibility (CI). “
152:
483:
Aksoy S, Weiss B, Attardo G (2008). "Paratransgenesis
Applied for Control of Tsetse Transmitted Sleeping Sickness".
1554:
158:
796:"Paratransgenesis: an approach to improve colony health and molecular insight in honey bees (Apis mellifera)?"
992:"Transgenesis and paratransgenesis to control insect-borne diseases: current status and future challenges"
170:
1501:"Using infections to fight infections: paratransgenic fungi can block malaria transmission in mosquitoes"
58:
24:
1445:
Gilbert JA, Medlock J, Townsend JP, Aksoy S, Ndeffo Mbah M, Galvani AP (March 2016). Remais JV (ed.).
524:
De Vooght L, Caljon G, Stijlemans B, De
Baetselier P, Coosemans M, Van den Abbeele J (February 2012).
164:
1157:
1052:
588:
430:
686:
Rodrigues FG, Santos MN, de Carvalho TX, Rocha BC, Riehle MA, Pimenta PF, et al. (April 2008).
740:
Mancini MV, Spaccapelo R, Damiani C, Accoti A, Tallarita M, Petraglia E, et al. (March 2016).
361:
Kotnis B, Kuri J (July 2016). "Evaluating the usefulness of paratransgenesis for malaria control".
262:
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967:
915:
396:
370:
251:
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Durvasula RV, Gumbs A, Panackal A, Kruglov O, Aksoy S, Merrifield RB, et al. (April 1997).
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328:
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Fang W, Vega-RodrĂguez J, Ghosh AK, Jacobs-Lorena M, Kang A, St Leger RJ (February 2011).
146:
136:
301:
Mancini MV, Damiani C, Short SM, Cappelli A, Ulissi U, Capone A, et al. (May 2020).
1161:
1056:
592:
434:
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1422:
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67:
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Killeen GF, McKenzie FE, Foy BD, Schieffelin C, Billingsley PF, Beier JC (May 2000).
903:
703:
453:
419:"Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria"
418:
307:
in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes"
1185:
1130:
919:
124:
971:
400:
31:
of a symbiont of the vector. The goal of this technique is to control vector-borne
28:
1228:
1101:
Sinkins SP, Gould F (June 2006). "Gene drive systems for insect disease vectors".
1463:
1363:
1263:
1007:
856:
653:
577:"Development of transgenic fungi that kill human malaria parasites in mosquitoes"
1447:"Determinants of Human African Trypanosomiasis Elimination via Paratransgenesis"
492:
487:. Advances in Experimental Medicine and Biology. Vol. 627. pp. 35–48.
1396:
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423:
Proceedings of the National Academy of Sciences of the United States of America
1313:
1039:
Weiss BL, Mouchotte R, Rio RV, Wu YN, Wu Z, Heddi A, Aksoy S (November 2006).
758:
384:
92:
323:
1212:
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600:
542:
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endosymbionts is a gene driven system and can also affect paratransgenesis.
44:
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510:
443:
392:
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963:
462:
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795:
128:
The procedure to generate transgenic insects by germ-line transformation.
20:
1413:
742:"Paratransgenesis to control malaria vectors: a semi-field pilot study"
266:
96:
36:
32:
1516:
246:
In order to perform paratransgenesis, there are several requirements:
1114:
39:
that prevent the vector species from transmitting the pathogen. The
375:
150:, a symbiont of tsetse flies found in the midgut and hemolymph of
135:
123:
1199:
Read AF, Thomas MB (2009). "Microbiology: Mosquitoes cut short".
275:
The association between vector and symbiont cannot be attenuated.
217:
During the process of conducting as a gene driven mechanism, the
196:
or laterally (due to feeding habits) when it comes to symbionts.
1347:"Viral paratransgenesis in the malaria vector Anopheles gambiae"
637:"Viral paratransgenesis in the malaria vector Anopheles gambiae"
140:
The procedure of insect transformation via transgenic symbionts.
40:
1345:
Ren X, Hoiczyk E, Rasgon JL (August 2008). Schneider DS (ed.).
1247:"How to make evolution-proof insecticides for malaria control"
990:
Coutinho-Abreu IV, Zhu KY, Ramalho-Ortigao M (March 2010).
80:
to express proteins such as Cecropin A that are toxic to
485:
Transgenesis and the Management of Vector-Borne Disease
43:
coding for these proteins are then introduced into the
985:
983:
981:
1302:
The American Journal of Tropical Medicine and Hygiene
794:Rangberg A, Diep DB, Rudi K, Amdam GV (July 2012).
1398:"Paratransgenic control of vector borne diseases"
838:Huang W, Wang S, Jacobs-Lorena M (August 2020).
789:
787:
412:
410:
1096:
1094:
1092:
735:
733:
731:
296:
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937:
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933:
931:
929:
833:
831:
8:
1402:International Journal of Biological Sciences
1240:
1238:
1148:infection into the mosquito Aedes aegypti".
478:
476:
474:
472:
19:is a technique that attempts to eliminate a
1245:Read AF, Lynch PA, Thomas MB (April 2009).
635:Ren X, Hoiczyk E, Rasgon JL (August 2008).
272:The engineered symbiont is stable and safe.
630:
628:
1524:
1472:
1462:
1421:
1372:
1362:
1321:
1272:
1262:
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1015:
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855:
811:
767:
757:
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608:
551:
541:
452:
442:
374:
332:
322:
50:The first example of this technique used
265:, such as through transformation with a
288:
1045:Applied and Environmental Microbiology
56:which is associated with the symbiont
1494:
1492:
7:
356:
354:
352:
800:Integrative and Comparative Biology
99:using fungi, viruses, or bacteria.
84:or that block the transmission of
14:
956:10.1046/j.1365-2583.1999.810125.x
278:Field delivery is easily handled.
66:is an important insect vector of
1451:PLOS Neglected Tropical Diseases
904:10.1046/j.0962-1075.2001.00276.x
844:PLOS Neglected Tropical Diseases
840:"Self-limiting paratransgenesis"
704:10.1111/j.1365-2583.2008.00791.x
35:. The first step is to identify
76:. The strategy was to engineer
1:
174:, and the salivary glands of
1464:10.1371/journal.pntd.0004465
1364:10.1371/journal.ppat.1000135
1264:10.1371/journal.pbio.1000058
1008:10.1016/j.parint.2009.10.002
857:10.1371/journal.pntd.0008542
654:10.1371/journal.ppat.1000135
269:containing the desired gene.
493:10.1007/978-0-387-78225-6_3
1576:
996:Parasitology International
91:Attempts are also made in
1499:Rasgon JL (August 2011).
1314:10.4269/ajtmh.2000.62.535
759:10.1186/s13071-016-1427-3
385:10.1016/j.mbs.2016.04.005
1103:Nature Reviews. Genetics
944:Insect Molecular Biology
892:Insect Molecular Biology
692:Insect Molecular Biology
530:Microbial Cell Factories
363:Mathematical Biosciences
324:10.3390/pathogens9050380
1213:10.1126/science.1168659
1170:10.1126/science.1165326
746:Parasites & Vectors
601:10.1126/science.1199115
543:10.1186/1475-2859-11-23
444:10.1073/pnas.94.7.3274
141:
129:
95:using bacteria and in
153:Glossina m. morsitans
139:
127:
1065:10.1128/aem.01507-06
263:genetically modified
182:being isolated from
171:Glossina brevipalpis
159:Glossina p. palpalis
27:populations through
1560:Genetic engineering
1505:Future Microbiology
1414:10.7150/ijbs.7.1334
1162:2009Sci...323..141M
1057:2006ApEnM..72.7013W
593:2011Sci...331.1074F
435:1997PNAS...94.3274D
59:Rhodococcus rhodnii
813:10.1093/icb/ics089
252:symbiotic bacteria
142:
130:
97:malaria mosquitoes
70:that is caused by
1517:10.2217/fmb.11.71
502:978-0-387-78224-9
73:Trypanosoma cruzi
53:Rhodnius prolixus
1567:
1555:Applied genetics
1539:
1538:
1528:
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1476:
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1335:
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815:
791:
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771:
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737:
726:
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715:
683:
677:
676:
666:
656:
632:
623:
622:
612:
587:(6020): 1074–7.
572:
566:
565:
555:
545:
521:
515:
514:
480:
467:
466:
456:
446:
414:
405:
404:
378:
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347:
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326:
298:
184:Gl. m. morsitans
165:Glossina austeni
17:Paratransgenesis
1575:
1574:
1570:
1569:
1568:
1566:
1565:
1564:
1545:
1544:
1543:
1542:
1498:
1497:
1490:
1457:(3): e0004465.
1444:
1443:
1439:
1395:
1394:
1390:
1357:(8): e1000135.
1344:
1343:
1339:
1295:
1294:
1290:
1257:(4): e1000058.
1244:
1243:
1236:
1198:
1197:
1193:
1156:(5910): 141–4.
1143:
1142:
1138:
1115:10.1038/nrg1870
1100:
1099:
1090:
1051:(11): 7013–21.
1038:
1037:
1033:
989:
988:
979:
941:
940:
927:
888:
887:
883:
850:(8): e0008542.
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793:
792:
785:
739:
738:
729:
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680:
647:(8): e1000135.
634:
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626:
574:
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569:
523:
522:
518:
503:
482:
481:
470:
416:
415:
408:
360:
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303:"Inhibition of
300:
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240:
231:
176:Gl. p. palpalis
122:
105:
12:
11:
5:
1573:
1571:
1563:
1562:
1557:
1547:
1546:
1541:
1540:
1488:
1437:
1408:(9): 1334–44.
1388:
1351:PLOS Pathogens
1337:
1288:
1234:
1207:(5910): 51–2.
1191:
1136:
1088:
1031:
977:
925:
898:(5): 397–405.
881:
827:
783:
727:
678:
641:PLOS Pathogens
624:
567:
516:
501:
468:
406:
348:
287:
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121:
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68:Chagas disease
13:
10:
9:
6:
4:
3:
2:
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1356:
1352:
1348:
1341:
1338:
1333:
1329:
1324:
1319:
1315:
1311:
1308:(5): 535–44.
1307:
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1299:
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1275:
1270:
1265:
1260:
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1155:
1151:
1147:
1140:
1137:
1132:
1128:
1124:
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1112:
1109:(6): 427–35.
1108:
1104:
1097:
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1080:
1075:
1070:
1066:
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997:
993:
986:
984:
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978:
973:
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965:
961:
957:
953:
950:(1): 125–32.
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747:
743:
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728:
723:
719:
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698:(2): 175–83.
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429:(7): 3274–8.
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198:Wolbachia
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