Medical Hypotheses 83 (2014) 60–61
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Could microbe stimulated maggots become a targeted natural antibiotics family? Wang Xue-yan a, Li Xiao-rong b,1, Gao Lei b, Wang Jiang-ning c,⇑ Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, The 9th Clinical College, PKU, Tieyi Road 10, Yangfangdian, Haidian District, Beijing 100038, China Luhe Teaching Hospital Of Capital Medical University, 101100, Xinhua Nanlu 82, Tongzhou District, Beijing, China Department of Orthopedics, Beijing Shijitan hospital, Capital Medical University, Beijing 100038, China
a r t i c l e
i n f o
Article history: Received 25 July 2013 Accepted 1 April 2014
a b s t r a c t Maggot debridement therapy plays an important role in treatment of diabetic foot ulcers and other chronic infectious wounds, cause of this is its extremely low drug resistance. However, the microbe stimulated maggot, we may call it a derivative of normal sterile maggot, could exhibit stronger bacterial or bactericidal effects. Methods of the pretreatment on maggot was different germ solution were artificially mixed and added with originally sterile maggots, the novel secretions were collected. Some of this have been demonstrated by plate test and telescope analysis. Thus, we hypothesize that maggot especially the larvae of Lucilia sericata was conducted as the germ irritant receptor, and diverse germs interacted with it, at last, novel secretions/excretions we got will offer a great help to the general surgery clinicians as well as researchers who are interested in novel antibiotics discovery. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction
Hypothesis
Diabetic foot ulcers and other chronic infectious wounds have been considered the intractable wound disease for a long time. Usually human beings will ask for help from antibiotics, inevitably high drug resistance will be accompanied with short anti infective effect. To present, a great deal of effort were put forth and more valuable achievements have been made. However, only few kind of maggot could exhibit antibacterial capacity so as to be studied by researchers. Presently, most of the reports are mainly about two parts, one is components analysis, the other is the study of the action mechanism. As for the former, research mainly focus into the defensins from the secretions of maggots, for example, chymotrypsin and lucifensin II (extracted from Lucilia sericata) [1,2], the expression of these defensins in various wound infections [3], the effect of the active compound on germs and their biofilm [4]. As for the latter, studies focus into identification of molecules enhancing some gene expression by MDT and its mechanism in intractable wound healing therapy [5], like formation of healthy granulation tissue observed during MDT results from the increased HGF [6], amino acid-like compounds presented in maggot ES were demonstrated proliferative effect, selectively on endothelial cells [7].
Our hypothesis proposed here is that L. sericata maggots or other available maggot pretreated by different germs would supply more targeted active secretions or potential compounds for surgery clinicians as well as researchers who are interested in novel antibiotics discovery.
⇑ Corresponding author. Tel.: +86 13681279113; fax: +86 010 63926669. 1
E-mail address: [email protected] (J.-n. Wang). Xiaorong Li is the joint first author.
http://dx.doi.org/10.1016/j.mehy.2014.04.008 0306-9877/Ó 2014 Elsevier Ltd. All rights reserved.
Theory of the hypotheses As we know, the clinical isolated strains could be more and more strong after antibiotics treatment, also we know that the key solution to the abuse of antibiotic was giving patients rational and most fitting drugs, not broad spectrum ones or normal targeted ones with strong side-effect. Thus, natural antibiotics could be the optimal choice, like sterile maggots secretions. Though much reports had demonstrated that maggot therapy could be successfully used to treat infected wounds involves breakdown of individual complement components, at least C3 and C4, in a cation-independent manner [8,9], where is the more flexible scientific treatment of wound infection? Ke-chun Jiang et al. [4] investigated the efficiency of ES from the maggot pretreated with Pseudomonas aeruginosa on the biofilms using microtitre plate assays and on bactericidal effect applying the colony-forming unit (CFU) assay [10]. They found that only 30 lg of the ES from the pretreated maggots group could greatly
X.-y. Wang et al. / Medical Hypotheses 83 (2014) 60–61
degrade the biofilm of P. aeruginosa. However, the CFU count of P. aeruginosa (Pseudomonas aeruginosa, the type species of the genus Pseudomonas (Migula)) was not decrease when compared to the ES from non pretreated maggots. Thus we are thinking that if researchers first let L. sericata maggot or other potential active maggots live in a bacterial suspension environment for 24 h, the environment could be a single germ like MRSA, also could be mixed germ suspension like MRSA and P. aeruginosa, actually more mixed germs would be fine. When maggot was stimulated by specific germs for 24 h, that its immune mechanism will automatically react to produce antagonistic stress response [11], its body neuron was activated as a part of odour-specific set of mushroom body neurons, and coincidently receives a reinforcement signal carried by aminergic neurons, the AC-cAMP-PKA cascade is triggered [12], then produce different secretions which may contain targeted active antibiotics. More importantly, the stimulator could be controlled by us, whichever are the isolated germs from clinical, preparing more potential pools of antibiotics may come true. Thus, we hypothesize that microbe stimulated maggot could be the family of natural antibiotics. Conclusion Based on the above, the secretions of microbe(clinically isolated) stimulated maggots could supply more potential antibiotics which most of all are targeted to the clinical intractable infection disease. The main principle behind this great hypothesis is that biological immune response of the maggots accelerate and different improved secretions release. Thus, intractable wound infection in hospital may will be treated ideally and satisfactorily.
Conflict of interest None declared.
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Grants sources This research granted by National Natural Science Foundation, organized by National Natural Science Foundation of China (81071586). References [1] Telford G, Brown AP, Kind A, English JS, Pritchard DI. Maggot chymotrypsin I from Lucilia sericata is resistant to endogenous wound protease inhibitors. Br J Dermatol 2011;164(1):192–6. [2] El Shazely B, Veverka V, Fucík V, Voburka Z, Zdárek J, Cerovsky´ V. Lucifensin II, a defensin of medicinal maggots of the blowfly Lucilia cuprina (Diptera: Calliphoridae). J Med Entomol 2013;50(3):571–8. [3] Valachová I, Bohová J, Pálošová Z, Takácˇ P, Kozánek M, Majtán J. Expression of lucifensin in Lucilia sericata medicinal maggots in infected environments. Cell Tissue Res 2013;353(1):165–71. [4] Jiang KC, Sun XJ, Wang W, Liu L, Cai Y, Chen YC, et al. Excretions/secretions from bacteria-pretreated maggot are more effective against Pseudomonas aeruginosa biofilms. PLoS One 2012;7(11):e49815. [5] Cazander G, Schreurs MW, Renwarin L, Dorresteijn C, Hamann D, Jukema GN. Maggot excretions affect the human complement system. Wound Repair Regen 2012;20(6):879–86. [6] Honda K, Okamoto K, Mochida Y, Ishioka K, Oka M, Maesato K, et al. A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production. Am J Physiol Cell Physiol 2011;301(6):C1423–30. [7] Bexfield A, Bond AE, Morgan C, Wagstaff J, Newton RP, Ratcliffe NA, et al. Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis. Br J Dermatol 2010;162(3):554–62. [8] Cazander Gwendolyn, Schreurs Marco WJ, Juke Gerrolt N, Nibbering Peter H. Maggot excretions and secretions reduce complement activation. Immunobiology 2012;217(11):1184. [9] Steenvoorde P, Jukema GN. The antimicrobial activity of maggots: in-vivo results. J Tissue Viability 2004;14(3):97–101. [10] van der Plas MJ, Jukema GN, Wai SW, Dogterom-Ballering HC, Lagendijk EL, van Gulpen C, et al. Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother 2008;61(1):117–22. [11] Foley PA, Luckinbill LS. The effects of selection for larval behavior on adult lifehistory features in Drosophila melanogaster. Evolution 2001;55(12):2493–502. [12] Diegelmann Soeren, Klagges Bert, Michels Birgit, Schleyer Michael, Gerber Bertram. Maggot learning and Synapsin function. J Exp Biol 2013;216(6):939–51.
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Could microbe stimulated maggots become a targeted natural antibiotics family? Wang Xue-yan a, Li Xiao-rong b,1, Gao Lei b, Wang Jiang-ning c,⇑ Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, The 9th Clinical College, PKU, Tieyi Road 10, Yangfangdian, Haidian District, Beijing 100038, China Luhe Teaching Hospital Of Capital Medical University, 101100, Xinhua Nanlu 82, Tongzhou District, Beijing, China Department of Orthopedics, Beijing Shijitan hospital, Capital Medical University, Beijing 100038, China
a r t i c l e
i n f o
Article history: Received 25 July 2013 Accepted 1 April 2014
a b s t r a c t Maggot debridement therapy plays an important role in treatment of diabetic foot ulcers and other chronic infectious wounds, cause of this is its extremely low drug resistance. However, the microbe stimulated maggot, we may call it a derivative of normal sterile maggot, could exhibit stronger bacterial or bactericidal effects. Methods of the pretreatment on maggot was different germ solution were artificially mixed and added with originally sterile maggots, the novel secretions were collected. Some of this have been demonstrated by plate test and telescope analysis. Thus, we hypothesize that maggot especially the larvae of Lucilia sericata was conducted as the germ irritant receptor, and diverse germs interacted with it, at last, novel secretions/excretions we got will offer a great help to the general surgery clinicians as well as researchers who are interested in novel antibiotics discovery. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction
Hypothesis
Diabetic foot ulcers and other chronic infectious wounds have been considered the intractable wound disease for a long time. Usually human beings will ask for help from antibiotics, inevitably high drug resistance will be accompanied with short anti infective effect. To present, a great deal of effort were put forth and more valuable achievements have been made. However, only few kind of maggot could exhibit antibacterial capacity so as to be studied by researchers. Presently, most of the reports are mainly about two parts, one is components analysis, the other is the study of the action mechanism. As for the former, research mainly focus into the defensins from the secretions of maggots, for example, chymotrypsin and lucifensin II (extracted from Lucilia sericata) [1,2], the expression of these defensins in various wound infections [3], the effect of the active compound on germs and their biofilm [4]. As for the latter, studies focus into identification of molecules enhancing some gene expression by MDT and its mechanism in intractable wound healing therapy [5], like formation of healthy granulation tissue observed during MDT results from the increased HGF [6], amino acid-like compounds presented in maggot ES were demonstrated proliferative effect, selectively on endothelial cells [7].
Our hypothesis proposed here is that L. sericata maggots or other available maggot pretreated by different germs would supply more targeted active secretions or potential compounds for surgery clinicians as well as researchers who are interested in novel antibiotics discovery.
⇑ Corresponding author. Tel.: +86 13681279113; fax: +86 010 63926669. 1
E-mail address: [email protected] (J.-n. Wang). Xiaorong Li is the joint first author.
http://dx.doi.org/10.1016/j.mehy.2014.04.008 0306-9877/Ó 2014 Elsevier Ltd. All rights reserved.
Theory of the hypotheses As we know, the clinical isolated strains could be more and more strong after antibiotics treatment, also we know that the key solution to the abuse of antibiotic was giving patients rational and most fitting drugs, not broad spectrum ones or normal targeted ones with strong side-effect. Thus, natural antibiotics could be the optimal choice, like sterile maggots secretions. Though much reports had demonstrated that maggot therapy could be successfully used to treat infected wounds involves breakdown of individual complement components, at least C3 and C4, in a cation-independent manner [8,9], where is the more flexible scientific treatment of wound infection? Ke-chun Jiang et al. [4] investigated the efficiency of ES from the maggot pretreated with Pseudomonas aeruginosa on the biofilms using microtitre plate assays and on bactericidal effect applying the colony-forming unit (CFU) assay [10]. They found that only 30 lg of the ES from the pretreated maggots group could greatly
X.-y. Wang et al. / Medical Hypotheses 83 (2014) 60–61
degrade the biofilm of P. aeruginosa. However, the CFU count of P. aeruginosa (Pseudomonas aeruginosa, the type species of the genus Pseudomonas (Migula)) was not decrease when compared to the ES from non pretreated maggots. Thus we are thinking that if researchers first let L. sericata maggot or other potential active maggots live in a bacterial suspension environment for 24 h, the environment could be a single germ like MRSA, also could be mixed germ suspension like MRSA and P. aeruginosa, actually more mixed germs would be fine. When maggot was stimulated by specific germs for 24 h, that its immune mechanism will automatically react to produce antagonistic stress response [11], its body neuron was activated as a part of odour-specific set of mushroom body neurons, and coincidently receives a reinforcement signal carried by aminergic neurons, the AC-cAMP-PKA cascade is triggered [12], then produce different secretions which may contain targeted active antibiotics. More importantly, the stimulator could be controlled by us, whichever are the isolated germs from clinical, preparing more potential pools of antibiotics may come true. Thus, we hypothesize that microbe stimulated maggot could be the family of natural antibiotics. Conclusion Based on the above, the secretions of microbe(clinically isolated) stimulated maggots could supply more potential antibiotics which most of all are targeted to the clinical intractable infection disease. The main principle behind this great hypothesis is that biological immune response of the maggots accelerate and different improved secretions release. Thus, intractable wound infection in hospital may will be treated ideally and satisfactorily.
Conflict of interest None declared.
61
Grants sources This research granted by National Natural Science Foundation, organized by National Natural Science Foundation of China (81071586). References [1] Telford G, Brown AP, Kind A, English JS, Pritchard DI. Maggot chymotrypsin I from Lucilia sericata is resistant to endogenous wound protease inhibitors. Br J Dermatol 2011;164(1):192–6. [2] El Shazely B, Veverka V, Fucík V, Voburka Z, Zdárek J, Cerovsky´ V. Lucifensin II, a defensin of medicinal maggots of the blowfly Lucilia cuprina (Diptera: Calliphoridae). J Med Entomol 2013;50(3):571–8. [3] Valachová I, Bohová J, Pálošová Z, Takácˇ P, Kozánek M, Majtán J. Expression of lucifensin in Lucilia sericata medicinal maggots in infected environments. Cell Tissue Res 2013;353(1):165–71. [4] Jiang KC, Sun XJ, Wang W, Liu L, Cai Y, Chen YC, et al. Excretions/secretions from bacteria-pretreated maggot are more effective against Pseudomonas aeruginosa biofilms. PLoS One 2012;7(11):e49815. [5] Cazander G, Schreurs MW, Renwarin L, Dorresteijn C, Hamann D, Jukema GN. Maggot excretions affect the human complement system. Wound Repair Regen 2012;20(6):879–86. [6] Honda K, Okamoto K, Mochida Y, Ishioka K, Oka M, Maesato K, et al. A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production. Am J Physiol Cell Physiol 2011;301(6):C1423–30. [7] Bexfield A, Bond AE, Morgan C, Wagstaff J, Newton RP, Ratcliffe NA, et al. Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis. Br J Dermatol 2010;162(3):554–62. [8] Cazander Gwendolyn, Schreurs Marco WJ, Juke Gerrolt N, Nibbering Peter H. Maggot excretions and secretions reduce complement activation. Immunobiology 2012;217(11):1184. [9] Steenvoorde P, Jukema GN. The antimicrobial activity of maggots: in-vivo results. J Tissue Viability 2004;14(3):97–101. [10] van der Plas MJ, Jukema GN, Wai SW, Dogterom-Ballering HC, Lagendijk EL, van Gulpen C, et al. Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother 2008;61(1):117–22. [11] Foley PA, Luckinbill LS. The effects of selection for larval behavior on adult lifehistory features in Drosophila melanogaster. Evolution 2001;55(12):2493–502. [12] Diegelmann Soeren, Klagges Bert, Michels Birgit, Schleyer Michael, Gerber Bertram. Maggot learning and Synapsin function. J Exp Biol 2013;216(6):939–51.
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