CEbiotech.com - Central European Biotechnology Portal
be visible on the BioBusiness market                  ISSN 2300-0228
Teichoic acids inhibitors in antibiotic recycling

Teichoic acids inhibitors in antibiotic recycling

Publish date: 2016-03-29

Current „boom” for new inhibitors of wall teichoic acids (WTA) of gram-positive bacteria has recently brought another scientific achievement. Tarocin A and B are novel compounds, which not having bactericidal action on their own, restore activity of several β-lactam antibiotics against methicillin-resistant staphylococci. Today, when antibiotics fade away, this is a very good news.

Tags: antibiotics , WTA , wall teichoic acids , MRSA , MRSE , tarocin

Wall teichoic acids (WTA) of gram-positive bacteria were described in a late 50s of XX. century and until recently were has been considered as structural elements of elusive biological function. As regards structure they are composed of polymeric ribitol phosphate (in Staphylococcus aureus) or glycerol phosphate (in Bacillus subtilis) and are connected to peptydoglycan structure.

            

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ref. Sewell EW, Brown ED 2014 

WTA synthesis is regulated by tar (teichoic acid ribitol) or tag (teichoic acid glycerol) genes products encoded in operons. These Tar and Tag proteins are anchored in cell membrane, where they subsequently catalyze a synthesis and elongation of polymer utilizing a lipid transporter – undecaprenol. Finally, synthesized structure is transported outside the cell membrane via TarGH, an ABC transporter, where it’s being anchored to peptydoglycan.

Deeper functional analysis of WTA has revealed their complex role in processes like bacterial proliferation, infection and antibiotic response. Today WTA are considered as an important element in cation binding, osmotic tolerance, binding of phages, cell shape determination and others. They are also an important virulence factor, which has been confirmed in animal models - ΔtarO mutants strains deprived of the first gene in WTA biosynthesis pathway are defective in colonization and infection process. As regards cell proliferation, WTA participate in peptydoglycan crosslinking and septum formation by recruiting PBP4 protein (penicillin binding protein 4).

This particular process is important as regards S. aureus resistance to β-lactam antibiotics. A classical mechanism of MRSA resistance to methicillin and other β-lactams involves modified PBP2 protein (PBP2A) which participate in primary peptydoglycan crosslinking. β-lactams specific for PBP2 block its catalytic function, but they do not block PBP2A. This modified form maintains the primary peptydoglycan crosslinking, which is then further catalyzed by PBP4. This model however, seems to be incomplete, because it engages teichoic acids. A synergy between β-lactams and ticlopidine – TarO inhibitor- has been observed in a research model. Pharmacologic blocking of WTA synthesis restores sesnsitivity to antibiotic even in a presence of PBP2A. This mechanism is presented on a scheme below:

Ref. Sewell EW, Brown ED 2014

What makes it possible to analyze the function of teichoic acids is a phenomenon of synthetic-viable interactions, which means the interaction between early and late tar genes’ products. ΔtarO mutants are viable, whereas mutation in tarGH is lethal. However, a simultaneous inactivation of tarO in ΔtarGH strains leads to restoration of viable phenotype in double mutants. This phenomenon is probably due to accumulation of undecaprenol-binding intermediates which are not further processed by late genes’ products in ΔtarGH – then undecaprenol is not available for another crucial processes like peptydoglycan synthesis, which leads to cell death. Simuntaneous inactivation of early genes (tarO or tarA) prevents initial steps of WTA synthesis and undecaprenol remains available for other biological processes. Described system, also called an “essential genes paradox” is a powerful tool for analysis of compounds disrupting teichoic acids at virtually any synthesis step. Till now, compounds like targocil (TarG inhibitor) or ticlopidine (TarO inhibitor) have been indentified. Observed synergistic effects of such inhibitors and known antibiotics (like in MRSA) may lead to so called “antibiotic recycling” in cases of lost antibiotic activity.

Very recently, Christopher Tan and co-workers from Merck Research Laboratories in New Jersey (USA), have analyzed 2.8 million synthetic small molecule compounds. In a presence of pharmacologic inhibitor of TarG of antibacterial activity, they identified substances restoring viability of S. aureus, thus inhibiting early steps of WTA biosynthesis. Compounds tarocin A and tarocin B belongs respectively to oxazolidinone and benzimidazole series types. As a target TarO protein has been identified.

Tarocin A and B alone do not reveal bactericidal activity, however they act in a synergistic way with chosen β-lactam antibiotics – imipenem and docloxacillin. Minimal inhibitory concentration of antibiotics against MRSA and MRSE (methicillin resistant Staphylococcus epidermidis) decreased more than 50-fold. Results from in vitro experiments has been confirmed using murine model.

Tan’s group also analyzed the emergence of spontaneous mutations gaining resistance to tarocin and its combination with antibiotics. Genome sequencing of mutants revealed 11 mutations in TarO gene potentially responsible for resistance to this type of inhibitors. To prevent a quick resistance formation well known from the history of antibiotics, Prof. Tan propose a combination of not two, but three different compounds, including for example inhibitor of different WTA synthesis step.

Usefulness of WTA inhibitors in antibiotic recycling gives a hope for beating a superbug 20 years faster. This is the time typically needed for development and introducing novel antibiotic to the market.

Monika Kossakowska-Zwierucho

Sources:

Sewell EW, Brown ED. Taking aim at wall teichoic acid synthesis: new biology and new leads for antibiotics. J Antibiot (Tokyo). 2014 Jan;67(1):43-51.

S. H. Lee, H. Wang, M. Labroli, S. Koseoglu, P. Zuck, T. Mayhood, C. Gill, P. Mann, X. Sher, S. Ha, S.-W. Yang, M. Mandal, C. Yang, L. Liang, Z. Tan, P. Tawa, Y. Hou, R. Kuvelkar, K. DeVito, X. Wen, J. Xiao, M. Batchlett, C. J. Balibar, J. Liu, J. Xiao, N. Murgolo, C. G. Garlisi, P. R. Sheth, A. Flattery, J. Su, C. Tan, T. Roemer, TarO-specific inhibitors of wall teichoic acid biosynthesis restore b-lactam efficacy against methicillin-resistant staphylococci. Sci. Transl. Med. 8, 329ra32 (2016)

https://www.newscientist.com/article/2080180-mrsa-superbugs-resistance-to-antibiotics-is-broken/

Comments:

Add comment
Guest
2018-06-19 23:27:39 +0200
BEST ONLINE LOVE SPELL CASTER TO GET YOUR EX LOVER, HUSBAND, WIFE, GIRLFRIEND OR BOYFRIEND BACK. ADD HIM UP ON WHATSAPP: +1 (859)-203-2241 Hello my respectable viewers, My names are EVELYN JENKINS and i'm from (FLORIDA, UNITED STATE) I am very happy to share this amazing testimony, i was hurt and heart broken when my husband left me with our kid, i was confused and didn't know what to do, i loved him so much, i tried all i could to bring him back but all my effort was in vain , on one faithful day i explained my problem to my friend, and she told me of a great love spell caster called "LORD JUMA" whom also make her pregnant when she was looking for a child, i never believed in spells but i have give a try to see if things will get better, i contacted LORD JUMA through the contact info my friend gave to me, after some hours the spell caster responded to me he told me to stay and gave me some instructions on what to do and i did exactly as i was told, to my greatest surprise, my husband who has not called me for a very 3 yrs , called me and start apologizing for all the wrongs he did to me and pleaded with me that he want to return home with me and the kids, now he loved me more than ever before, my respectable viewers brothers and sisters if you are passing through any kind of problem contact him and i give you 100% guarantee that he will solve your problems. this is his contacts: mercyfullsolutionhome@yahoo.com or mercyfullsolutionhome@gmail.com his website: http://mercyfullsolutionhome.website2.me/ or http://mercyfullsolutionhome.blogspot.com or https://evelynjankins.blogspot.com/ add him up on whatsApp at: +1 (859)-203-2241
Gregorykushi
2018-02-24 19:31:49 +0100
Buy Palbace Lemon Quaaludes,BOTOX,XANAX,VA, We have medications for the treatment of chronic back pains, cough, anxiety,panic disorder, depression, erectile dysfunction, dysfunction,adhd,narcolepsy, obesity,depression, fatigue,Weight Loss supplement and more online (no prescription required).We sell quality medications online at affordable and discount prices. Fast and secure overnight delivery. We are ready to sell minimum quantities and large supplies of our product worldwide (SHIPPING IS WORLDWIDE). Below is a list of some of our product : Klonopin 1mg,2mg Ativan Opama 10mg,20mg,30mg,40mg Ambien Soma 350mg Oxycotin Hydrocodone Roxicodone Percocert Lorazepam 2.5 mg (Ativan) Clonazepam 2 mg (Rivotril) Valium 2mg,5mg and 10mg Fentalyn patches Tramadol (Ultram) 50mg etc........ We offer: - Good quality Medications - Good and affordable prices. - Fast and Reliable delivery -Tracking Available! -Tracking numbers available with references. - Various shipping option (Overnight and Airmail). -Shipping secure and discreet ,Delivery time OVERNIGHT & 1-5 days depending on location. - Buy with and without Prescription Required! -Additional Discounts on Bulk Orders - Buy Direct and Save Time and Money! - 100% Customer Satisfaction Guaranteed ! Contact via details below: EMAIL.....jamesbernal2001@gmail.com CONTACT NUMBER...9046868791
Cyshine
2018-02-11 05:08:11 +0100
Thanking God for Using great Dr. Breeze to heal me from Herpes and Adenomiosis with the use of his powerful miracle herbs, I have been in this illness for more than five years now and I have tried all possible best I can to get cured but nothing is working out,I have spent alot of money but nothing is still coming out, on one blessed morning, when listening to News in the TV set, I saw a man giving wonderful testimonies about Dr. Breeze and his email and phone number was displayed in the TV set so I have to write down and immediately I contacted the Great Doctor, after speaking with him, he asked for my information's and told me I had to pay for the medicine, which I sent him the morning, after an hour time I got the tracking number from him which he has used to sent the medicine through DHL, after three days I received it and used accordingly the way he directed me after one month of using the medicine, I went three different hospitals for check up, surprisingly, the Doctor shake my hand and told me Congratulations that you are cure totally from Herpes and Adenomiosis and this is the seventh month now, I went for check up again the same test result that I am cured totally, I want to Thank God for sending this Doctor to my life and as he has did that, I am here to tell the world about him because you might need his help from any condition to the other and I believe and know it Dr. Breeze can help you get out from any situation you are passing through in Life. His contact's information's are Email: DR.BREEZEHOME@GMAIL.COM WEBSITE: http://drbreezespiritualhome.webs.com/ WHATSAPP NO: +2348164848027 I am waiting to hear your own testimonies friends
Guest
2017-11-11 20:13:38 +0100
MY Joy is back to me after a very long time which i and my ex separated since i was alone my life change,every thing about me change a friend of mine gave me an email address and told me that this was the email address she contacted when she was in the same problem so i contacted the email i got a reply he ask me to send him my number so i did he was a man call PRIEST ADE he is a spell caster he casted a spell for me and told me that within two day that my ex we be back for good within that two days my ex was back, i and my ex just got married. few week back, you can contact him at ancientspiritspellcast@yahoo.com or ancientspiritspellcast@gmail.com WhatsApp +2347059715465 once again thank you PRIEST ADE
Guest
2017-06-16 16:51:04 +0200
My name is SYLVIA, I never thought I will smile again, My husband left me with two kids for one year, All effort to bring him back failed I thought I'm not going to see him again not until I met a lady called Jesse who told me about a spell caster called Dr.KEN, She gave me his email address and mobile number and I contacted him and he assured me that within 48hours my husband will come back to me, In less than 48hours my husband came back started begging for forgiveness saying it is the devils work, so I'm still surprise till now about this miracle,i couldn't conceive but as soon as the spell was cast,i became pregnant and gave birth to my third child(Michelle) if you need any assistance from him you can contact him via:email [drkenlovespell@gmail.com] his telephone number is +19038485301
Guest
2017-06-04 11:41:28 +0200
What a miracle to have my ex back,my name is mary benny and i need to share this great testimony... I just want to say thanks Dr gbojie for taking time to help me cast the spell that brings back my ex lover {now my husband},who suddenly lost interest in me after six month of engagement,but today we are married and we are more happier than never before, I am really short of words and joyful, and i don't know how much to my appreciation to you doctor gbojie you are a God sent to restore broken relationship.he deeply enjoy helping people achieve their desires, find true love,getting their ex lovers back,stop abusive relationships,find success,attract happiness,find soul mates and more,contact him today. and let him show you the wonders and amazement of his Love Spell System. He deliver results at his best in real spell casting,email him for help on gbojiespiritualtemple@gmail.com you can also call him on +2349066410185 contact him on his web site https://gbojiespelltemple.wordpress.com
Guest
2017-06-01 23:34:06 +0200
I am here to spread this good news to the entire world on how Dr. Ken of supersolutionhome1@gmail.com or supersolutionhom@yahoo.com helped me solve my infertility problem and i am so happy now that i am now a mother because for over 4 years i have been trying to get pregnant and needed help, i and my husband always go for medical check up and the doctor always say that the both of us are fine and i have no where else to get help from and all hope was almost lost until one day i visited a friend of mine and i told her what i was passing through and she introduce me to this great spell caster called Dr. Ken who helped her when she was in need of help, so i took a try to contact Dr. Ken through his email and i explain all my problem to him and after we have talked he perform an infertility spell for me and after that he told me what i should do, and i followed the instruction he gave and after that he instructed to sleep with my husband and also i followed the instruction and he said that the next week i should go for medical check up and the doctor confirmed that i was 4 months pregnant and i was so happy that all my sorrows were gone for ever, i am so very happy now and also you need any kind of help or the same line with mine, contact Dr. Ken on his email: supersolutionhome1@gmail.com or supersolutionhom@yahoo.com or view through his website and Contact him there: http://supersolutionhome.webs.com Call his phone number +2348074433380
Guest
2017-05-31 22:07:30 +0200
I am here to spread this good news to the entire world on how Dr. Ken of supersolutionhome1@gmail.com or supersolutionhom@yahoo.com helped me solve my infertility problem and i am so happy now that i am now a mother because for over 4 years i have been trying to get pregnant and needed help, i and my husband always go for medical check up and the doctor always say that the both of us are fine and i have no where else to get help from and all hope was almost lost until one day i visited a friend of mine and i told her what i was passing through and she introduce me to this great spell caster called Dr. Ken who helped her when she was in need of help, so i took a try to contact Dr. Ken through his email and i explain all my problem to him and after we have talked he perform an infertility spell for me and after that he told me what i should do, and i followed the instruction he gave and after that he instructed to sleep with my husband and also i followed the instruction and he said that the next week i should go for medical check up and the doctor confirmed that i was 4 months pregnant and i was so happy that all my sorrows were gone for ever, i am so very happy now and also you need any kind of help or the same line with mine, contact Dr. Ken on his email: supersolutionhome1@gmail.com or supersolutionhom@yahoo.com or view through his website and Contact him there: http://supersolutionhome.webs.com Call his phone number +2348074433380
Guest
2017-05-30 06:17:17 +0200
my mouth is full of testimony is just like a dream but is real all thanks to papa Dr ODUMA. I will continue to share this testimony sir still the whole world had of it. i am out here to spread this good news to the entire world on how I got my ex husband back.I was going crazy when my husband left me and my two kids for another woman last month, But i complained to my colleague in my place of work and she discuss with me her experience too and how she over come with the help of papa Dr ODUMA the great messenger God is using to help people, I narrated my problem to Dr ODUMA about how my Husband left me and my two kids and also how i needed to get a job in a very big company.He only said to me that i have come to the right place were i will be getting my heart desire without any side effect.He told me what i need to do,After it was been done,24 hours later,My Ex Husband called me on the phone and was saying sorry for living me and the kids before now and one week after my Husband called me to be pleading for forgiveness,I was called for interview in a very big company here in Washington DC were i needed to work as the managing director..I am so happy and overwhelmed that i have to tell this to the entire world to contact odumaspelltemple0@gmail.com on his personal email address or +2348182394798/ and get all your problem solve..No problem is too big for him to solve
Guest
2017-05-30 06:16:11 +0200
I am Mrs. VANISSA DANIEL from USA, i want to share a testimony of my life to every one. i was married to my husband, and i love him so much we have been married for 4 years now with three kids. when he went for a vacation to RUSSIAN he meant a lady called SANDRA, he told me that he is no longer interested in the marriage any more. i was so confuse and seeking for help, i don't know what to do until I met my friend miss joy and told her about my problem. she told me not to worry about it that she had a similar problem before and introduce me to a man called prophet jeremiah omoto who is man of God for her ex and bring him back to her after 2days. Miss joy ask me to contact prophet jeremiah omoto I contacted him to help me bring back my husband and he ask me not to worry about it that the God of his fore-fathers will fight for me. He told me by two days he will re-unite me and my husband together. After two day my husband called and told me he is coming back to sought out things with me, I was surprise when I saw him and he started crying for forgiveness. Right now I am the happiest woman on earth for what this great MAN OF God did for me and my husband, you can contact prophet jeremiah omoto on any problem in this world, he is very nice, here is his EMAIL contact: prophetmercyland@gmail.com or watch him television marcylandtv com or +2347055176615 .
Guest
2017-05-17 23:33:59 +0200
Hi My name is "Goyal Abhishek" I was married for 9years with Keshika and we had a kid together. Things started getting ugly and we had fights and arguments almost every time... it got worse at a point that she filed for divorce... I tried my best to make her change her mind & stay with me. She moved out of the house and still went ahead to file for divorce... I pleaded and tried everything but still nothing worked. The breakthrough came when my friend introduced me to this wonderful, great spell caster who has helped him and his wife solve their infertility problem... I have never been a fan of things like this but just decided to try reluctantly cause I was desperate and left with no choice... He did special prayers for me... Within 2 days she called me and was sorry for all the emotional trauma she had cost me, she moved back to the house and we continue to live happily. what a wonderful miracle Dr. Ken did for me and my family. I have introduced him to a lot of couples with problems across the world and they have had good news... I strongly believe someone out there need's his help (supersolutionhome1@gmail.com or supersolutionhom@yahoo.com)so make extra effort to save your marriage/relationship if it's truly worth it. call him +2348074433380 His website: http://supersolutionhome.webs.com MY BLOG IS: http://goyalabhishek585.skyrock.com
Guest
2017-05-16 07:21:16 +0200
Hi My name is "Goyal Abhishek" I was married for 9years with Keshika and we had a kid together. Things started getting ugly and we had fights and arguments almost every time... it got worse at a point that she filed for divorce... I tried my best to make her change her mind & stay with me. She moved out of the house and still went ahead to file for divorce... I pleaded and tried everything but still nothing worked. The breakthrough came when my friend introduced me to this wonderful, great spell caster who has helped him and his wife solve their infertility problem... I have never been a fan of things like this but just decided to try reluctantly cause I was desperate and left with no choice... He did special prayers for me... Within 2 days she called me and was sorry for all the emotional trauma she had cost me, she moved back to the house and we continue to live happily. what a wonderful miracle Dr. Ken did for me and my family. I have introduced him to a lot of couples with problems across the world and they have had good news... I strongly believe someone out there need's his help (supersolutionhome1@gmail.com or supersolutionhom@yahoo.com)so make extra effort to save your marriage/relationship if it's truly worth it. call him +2348074433380 His website: supersolutionhome.webs.com MY BLOG IS: http://goyalabhishek585.skyrock.com
Guest
2017-03-02 13:08:29 +0100
BE CAREFUL HERE MANY OF THE DOCTORS HERE ARE SCAM,MOST TESTIMONIES OF MOST SPELL CASTER HERE MUST BE IGNORE.BECAUSE THEY ARE SCAM I MEAN REAL SCAM WHICH I WAS A VICTIM.I GOT RIPPED OF THREE THOUSANDS DOLLARS BY 4 CASTERS BECAUSE I WAS SO ANXIOUS TO GET MY WIFE BACK AFTER SHE LEFT ME FOR ALMOST 2 YEARS WITH OUR 4 YEARS OLD SON JERRY,, I HAVE PAID OVER $3000 ON SPELL CASTING AND COURIER AND NOTHING HAVE WORK FOR ME UNTIL ONE FAITHFUL DAY I GOT IN CONTACT WITH MADAM SOLUTION WHO DID WHAT I CALLED MAGIC BECAUSE I CONTACTED HER ON FRIDAY AND AFTER GIVEN HER MY DETAILS AND $245 FOR THE SPELL CASTING MY WIFE CALLED ME ON SUNDAY AND NOW WE ARE BACK TOGETHER AGAIN IF YOU NEED SIMILAR HELP THEN CONTACT HER NOW VIA EMAIL AT (magic.lovespel@reincarnate.com) .
Guest
2017-02-19 22:54:22 +0100
I was with my ex for 3 years n 6mthns n he cheated on me so we split, before he left me, we were planing to get married in the future, I loved him so much but I became tired of him lying to me every time he opens his mouth, I went into search for help in the internet, I tried many different spells from almost every place locally as well as online and none of them worked, I almost gave up hope because I thought i will never see my lover again forever, one day i saw some testimony about this powerful spell caster Dr. Todd i emailed him and i asked him to help me bring back my lover and he did A Lover Spell for me And after some days, my lover returned back to me I'd like to say that i got a positive result from (manifestspellcast@gmail.com) ever since i used his love spell, my lover have learned to appreciate me more and he doesn't take me for granted anymore.
Guest
2017-01-03 21:06:59 +0100
My Husband and i have been trying to have a child for two years, and the trying, fertility doctors, tests, hormone shots and miscarriages had begun to be a stifling force to our marriage. My husband was ready to give up and i was emotionally exhausted. A friend simply mentioned a fertility spell as a joke one day (don't joke with a hormonal woman, first of all!) and i decided to look into it. Dr. Ken agreed to take my case and help me to conceive with a fertility spell. Considering the cost of the treatment i have already gone through,the fee was okay, and my hopes were extremely high. Dr. Ken understood and knew the devastation and conquered feeling that hopeful mothers with fertility issues were likely to go through because he has been helping women in my type of case before i came to him.and i could feel his sincerity and his hope for me. We talked for a few days back and forth, and we finally decided to go ahead. I continued to have conception on my mind, but i felt my anxiety release a little by little. In my heart, I knew that it would work. After five weeks, I took a pregnancy test and it was positive! I wanted to wait to share the positive news, since I have repeatedly had miscarriages in my first trimester, but I am now seven months pregnant with a healthy baby girl. I'm glad that my friend made the joke that she did, and I'm equally thrilled my frantic hormonal brain took it seriously. All thanks to Dr. Ken. If you are having issues getting pregnant contact Dr. Ken today via email: supersolutionhome1@gmail.com or supersolutionhom@yahoo.com Via website: supersolutionhome.webs.com
Guest
2017-01-03 11:42:55 +0100
My Husband and i have been trying to have a child for two years, and the trying, fertility doctors, tests, hormone shots and miscarriages had begun to be a stifling force to our marriage. My husband was ready to give up and i was emotionally exhausted. A friend simply mentioned a fertility spell as a joke one day (don't joke with a hormonal woman, first of all!) and i decided to look into it. Dr. Ken agreed to take my case and help me to conceive with a fertility spell. Considering the cost of the treatment i have already gone through,the fee was okay, and my hopes were extremely high. Dr. Ken understood and knew the devastation and conquered feeling that hopeful mothers with fertility issues were likely to go through because he has been helping women in my type of case before i came to him.and i could feel his sincerity and his hope for me. We talked for a few days back and forth, and we finally decided to go ahead. I continued to have conception on my mind, but i felt my anxiety release a little by little. In my heart, I knew that it would work. After five weeks, I took a pregnancy test and it was positive! I wanted to wait to share the positive news, since I have repeatedly had miscarriages in my first trimester, but I am now seven months pregnant with a healthy baby girl. I'm glad that my friend made the joke that she did, and I'm equally thrilled my frantic hormonal brain took it seriously. All thanks to Dr. Ken. If you are having issues getting pregnant contact Dr. Ken today via email: supersolutionhome1@gmail.com or supersolutionhom@yahoo.com Via website: supersolutionhome.webs.com
Enoch davies
2016-12-22 14:35:53 +0100
GET YOUR EX WIFE, EX GIRLFRIEND, EX BOYFRIEND AND SOLVE ALL TYPE OF PROBLEM THROUGH COVENANTSOLUTIONTEMPLE@GMAIL.COM. My name is Enoch Davies .my wife and I got married 6 years ago and we were so much in love with each other, we have 2 kids(josh and rebecca). One day my wife came back home from her friends place and she told me that she wants us to file for a divorce that she's no longer interested in our marriage, i was surprise and everything seem to me like a joke. after then i tried all my best to get her back but there was no way. but to no avail, my heart was broken, i wondered whats happening .i was on facebook when i saw a post on how Dr Ewan helped a lady to bring back her lost husband. i was scared but because i love my wife so much and I am ready to do anything to bring her back. I decided to give it a try by contacting him via email:covenantsolutiontemple@gmail.com, So when i contacted him i narrated everything to him and he said my case is not a serious one that my husband will come back to me within 18 hours if i believe in his power.he told me to do some things to do which i did before 18 hours, my wife called me on phone and was crying for forgiveness. right now we are now a new branded family with more happiness, we are even going on vacation on xmas. please if any one of you out there is passing through same issue in your marriage, relationship issues contact Dr Ewan today or call or add him on whatsapp on +234905735398 . contact him today on covenantsolutiontemple@gmail.com now. . I will keep on sharing the good news about this. Thanks Dr.
Guest
2016-12-22 13:12:14 +0100
A SOLUTION ON HOW TO GET MY HUSBAND BACK FROM CHEATING http://adagbaspiritualtem9.wixsite.com/mysite HI My Name is Jennifer , I wish to share my testimonies with the general public about what this man called dr ADAGBA of( adagbaspiritualtemple@gmail.com has just done for me , this man has just brought back my lost family to me with his great spell, I was married to this man called James we were together for a long time and we loved our self’s but when I was unable to give hIM a child for 6 years he left me and told me he can’t continue anymore then I was now looking for ways to get him back until a friend of mine who told me about this man and gave his contact email adagbaspiritualtemple@gmail.com ) then you wont believe this when I contacted this man on my problems he prepared this spell cast and bring my lost husband back and after a month I miss my month and go for a test and the result stated tha i was pregnant am so happy today because i am now a mother of 2 baby girl and a boy, thank you once again the great ADAGBA for what you have done for me, if you are out there passing through this same kind of problems or any kinds of pain at all you can contact him today on his mail (adagbaspiritualtemple@gmail.com or WHATSAPP him via: +2349057354407 his website, http://adagbaspiritualtem9.wixsite.com/mysite and he will also help you as well.
How to get your ex lover back
2016-12-01 23:10:10 +0100
Get your ex lover back before Xmas and new year urgently(templeofjoyandprosperity@gmail.com) Hello, i am Jessica Wayne from TX, USA. Life without my husband was a real mess for me and my children I am so happy to get my Ex back through the help of Dr Noble the spell caster . My greatest surprise was that 48 hours after the Doctor prepared the spell for me, my husband who has abandoned me for 4 years suddenly called me unexpectedly and am so happy that we have come to become one again through the help of Dr Noble and am so happy to be with my husband once again. Dr Noble is a very wonderful spell caster, you can contact him if you need his assistant because i know he can also help you. contact him through his email: templeofjoyandprosperity@gmail.com immediately
Jennifer234
2016-10-27 07:03:15 +0200
Powerful and real love spell to get your ex gf back stop your bf from cheating on you also work fast Me and my boyfriend were together for 8 months & its been 6 months since we separated. I still love him, but some how feel its unfair. Why love someone who ovb doesnt love you back? Ive prayed & prayed for these months & nothing. He is still with his new girlfriend(whom he lives with) but it doesnt mean I have to look for help The first weeks after the break up I was in my knees praying looking for help, them i fine a comment online how a spell caster help to restored relationship get ex lover back, ” so i decided to give a try coz i love my boyfriend so much. so i contacted Dr happy tell him all my problem and he gave me 100%guarantee that i will have my boyfriend back after the spell so i was gifted and lucky to have contacted him i did every thing he ask of me and to my greatest surprise a day after the spell my boyfriend call me and apology for what he did to me and ask for my forgiveness to come back home for me, I get really hurt & go through those moments in which he left me after all Dr happy did for me, i forgive him and he come back home with more love and happiness all thanks to Dr happy the real Africa spell caster who help to bring ex lover back, restored broken relationship and marriage. plz if you need any help contact him on happylovespell2@gmail.com. You see in conclusion you have to just trust the process, Dr happy is a good real spell caster so call him or add him on whats-app +2348133873774 Jennifer Marian Base in Texas Usa
Guest
2016-08-29 18:32:34 +0200
I am here to spread this good news to the entire world on how Dr. Ken of supersolutionhome1@gmail.com or supersolutionhom@yahoo.com helped me solve my infertility problem and i am so happy now that i am now a mother because for over 4 years i have been trying to get pregnant and needed help, i and my husband always go for medical check up and the doctor always say that the both of us are fine and i have no where else to get help from and all hope was almost lost until one day i visited a friend of mine and i told her what i was passing through and she introduce me to this great spell caster called Dr. Ken who helped her when she was in need of help, so i took a try to contact Dr. Ken through his email and i explain all my problem to him and after we have talked he perform an infertility spell for me and after that he told me what i should do, and i followed the instruction he gave and after that he instructed to sleep with my husband and also i followed the instruction and he said that the next week i should go for medical check up and the doctor confirmed that i was 4 months pregnant and i was so happy that all my sorrows were gone for ever, i am so very happy now and also you need any kind of help or the same line with mine, contact Dr. Ken on his email: supersolutionhome1@gmail.com or supersolutionhom@yahoo.com or view through his website and Contact him there: http://supersolutionhome.webs.com Call his phone number +2348074433380
Guest
2016-06-15 11:02:15 +0200
GREAT THANKS TO DR. SAM THAT HELPED SAVED MY MARRIAGE AND HELPED ME GET PREGNANT. I'm Stephanie Williams from USA, for over 4 years now of my marriage i have been trying to get pregnant, this almost made my husband to divorce me because my mother in-law was planning to get him another girl, i was always crying everyday because my marital life way going down. My mother in-law made my husband believe that i was the cause of us being able to give birth, i was always crying, my heart was broken into pieces. My husband and I have been seeing a fertility specialist. We have done one IUI with no luck. My husband has a sperm count which goes up and down,the doctor has recommended him taking the Proxeed supplement which he is doing over 3 years with no change in the situation my husband who has low sperm count? It just seems to me that if the sperm are unable to fertilize the egg it will not matter how many are produced. I am was so confused until i contacted this powerful spell caster online who I saw a number of testimonies of how he has help so many of them so I sent DR. SAM a mail and I told him all my sorrows and pain he replied me and ask me not to cry any more that he will help, he sent me some instructions and caution, DR. SAM (the spell caster) performed the ritual rights and I bought some items to complete the rights and he told me to have sex with my husband within 2weeks of doing this I felt dizzy and I went to the doctor and it was confirm that I was pregnant thanks to DR. SAM spell temple now am a mother of a bouncing baby boy and joy has been restored to my marital life and am very happy, no more stress from my mother in-law. If any one needs such help don’t wait all life time to get help in getting pregnant contact DR. SAM now on his personal email : miraclefertilitysolutiontempl1@gmail.com or miraclefertilitysolutiontemple@yahoo.com or through his website: http://miraclefertilityso.wix.com/dr-sam You can also contact him through his mobile: +2348110496031. Contact him now for pregnancy spell and love spell to bring back your ex lover http://stephwilliam11.skyrock.com/
Guest
2016-06-15 11:01:59 +0200
GREAT THANKS TO DR. SAM THAT HELPED SAVED MY MARRIAGE AND HELPED ME GET PREGNANT. I'm Stephanie Williams from USA, for over 4 years now of my marriage i have been trying to get pregnant, this almost made my husband to divorce me because my mother in-law was planning to get him another girl, i was always crying everyday because my marital life way going down. My mother in-law made my husband believe that i was the cause of us being able to give birth, i was always crying, my heart was broken into pieces. My husband and I have been seeing a fertility specialist. We have done one IUI with no luck. My husband has a sperm count which goes up and down,the doctor has recommended him taking the Proxeed supplement which he is doing over 3 years with no change in the situation my husband who has low sperm count? It just seems to me that if the sperm are unable to fertilize the egg it will not matter how many are produced. I am was so confused until i contacted this powerful spell caster online who I saw a number of testimonies of how he has help so many of them so I sent DR. SAM a mail and I told him all my sorrows and pain he replied me and ask me not to cry any more that he will help, he sent me some instructions and caution, DR. SAM (the spell caster) performed the ritual rights and I bought some items to complete the rights and he told me to have sex with my husband within 2weeks of doing this I felt dizzy and I went to the doctor and it was confirm that I was pregnant thanks to DR. SAM spell temple now am a mother of a bouncing baby boy and joy has been restored to my marital life and am very happy, no more stress from my mother in-law. If any one needs such help don’t wait all life time to get help in getting pregnant contact DR. SAM now on his personal email : miraclefertilitysolutiontempl1@gmail.com or miraclefertilitysolutiontemple@yahoo.com or through his website: http://miraclefertilityso.wix.com/dr-sam You can also contact him through his mobile: +2348110496031. Contact him now for pregnancy spell and love spell to bring back your ex lover http://stephwilliam11.skyrock.com/
Guest
2016-06-15 11:01:43 +0200
GREAT THANKS TO DR. SAM THAT HELPED SAVED MY MARRIAGE AND HELPED ME GET PREGNANT. I'm Stephanie Williams from USA, for over 4 years now of my marriage i have been trying to get pregnant, this almost made my husband to divorce me because my mother in-law was planning to get him another girl, i was always crying everyday because my marital life way going down. My mother in-law made my husband believe that i was the cause of us being able to give birth, i was always crying, my heart was broken into pieces. My husband and I have been seeing a fertility specialist. We have done one IUI with no luck. My husband has a sperm count which goes up and down,the doctor has recommended him taking the Proxeed supplement which he is doing over 3 years with no change in the situation my husband who has low sperm count? It just seems to me that if the sperm are unable to fertilize the egg it will not matter how many are produced. I am was so confused until i contacted this powerful spell caster online who I saw a number of testimonies of how he has help so many of them so I sent DR. SAM a mail and I told him all my sorrows and pain he replied me and ask me not to cry any more that he will help, he sent me some instructions and caution, DR. SAM (the spell caster) performed the ritual rights and I bought some items to complete the rights and he told me to have sex with my husband within 2weeks of doing this I felt dizzy and I went to the doctor and it was confirm that I was pregnant thanks to DR. SAM spell temple now am a mother of a bouncing baby boy and joy has been restored to my marital life and am very happy, no more stress from my mother in-law. If any one needs such help don’t wait all life time to get help in getting pregnant contact DR. SAM now on his personal email : miraclefertilitysolutiontempl1@gmail.com or miraclefertilitysolutiontemple@yahoo.com or through his website: http://miraclefertilityso.wix.com/dr-sam You can also contact him through his mobile: +2348110496031. Contact him now for pregnancy spell and love spell to bring back your ex lover http://stephwilliam11.skyrock.com/
Love
2016-06-15 05:41:10 +0200
Today has being the most happiest day of my life after 1 year of sadness and sorrow without being with the one i love, i tried all my possible best to make sure i make my lover happy but it never seems to work out well it was like am doing everything in vain but all thanks to Lord Alika for coming to change all my worries and sadness to Joy. i knew the great man when i read some wonderful reviews about Lord Alika how he has helped a lots of people on there relationship problem i was reading a magazine which then i saw great testimonies as well which then i decided not to waste time.he told me not to worry that he assures me that within 48 hours everything would be sorted out i believed Lord Alika so much because i believe he can't fail me and i sent him all my details. Truly Lord Alika never failed me,my husband who left me for good a year come back to me. My husband and i have been living contentedly since this spell caster reunited us together with his love spells. Thank you so so so much Lord Alika for your powerful spells. expressions are not sufficient to say thank you. here is his email address lordalikaspelltemple@yahoo.co.uk or http://lordalikaspelltemp8.wix.com/http call him +13217666393
Guest
2016-05-11 04:59:47 +0200
Hi everyone, I'm so excited.! Life without my boyfriend was a real mess for me,What on Earth will i do to thank Dr.Unity for his help? he is wonderful and has a good heart. He is like a God on Earth and i really do not know what to do to thank him for helping me regain my boyfriend love back with his spell. After being in relationship with my boyfriend (Andrew) for 3 years, he broke up with me, I did everything possible to bring him back but all was in vain, I wanted him back so much because of the love I have for him, I begged him with everything, I made promises but he refused. I explained my problem to someone online and she suggested that I should rather contact a spell caster that could help me cast a spell to bring him back but I am the type that never believed in spell, I had no choice than to try it, I mailed the spell caster, and he told me there was no problem that everything will be okay before two days, that my ex will return to me before two days, he cast the spell and surprisingly in the second day, it was around 4pm. My ex called me, I was so surprised, I answered the call and all he said was that he was so sorry for everything that happened, that he wanted me to return to him, that he loves me so much. I was so happy and went to him, that was how we started living together happily again. Since then, I have made promise that anybody I know that have a relationship problem, I would be of help to such person by referring him or her to the only real and powerful spell caster who helped me with my own problem and if you have any problem contact Dr.Unity,I guarantee you that he will help you, his Email is: Unityspelltemple@gmail.com or call him on +2348072370762 you can email him if you need his help in your relationship or any other problem like wining lottery your problem can never remain the same again, it will turn a thing of the past in your life.I am Katy Brown,I live here in USA at 1934 Sunny-Dale Ave,San Francisco,Ca 94134 , United States.
Guest
2016-04-17 07:11:03 +0200
I want to share my great experience to the whole world about how i got my lover back. I promise to share this testimony all over the world once my boyfriend return back to me, and today with all due respect i want to thank Lord Alika for bringing joy and happiness to my relationship and my family. I want to inform you all that there is a spell caster that is real and genuine. I never believed in any of these things until i loosed my boyfriend, I required help until i found lordalikaspelltemple@yahoo.co.uk a grate spell caster, And he cast a love spell for me, and he assured me that I will get my boyfriend back in two days after the spell has been cast. two days later, my phone rang, and so shockingly, it was my boyfriend who has not called me for past 6 months now, and made an apology for the heart break, and told me that he is ready to be my back bone till the rest of his life with me. Lord Alika released him up to know how much i loved and wanted him. And opened his eyes to picture how much we have share together. As I'm writing this testimony right now I'm the most happiest girl on earth and me and my boyfriend is living a happy life and our love is now stronger than how it were even before our break up. So that's why I promised to share my testimony all over the universe.All thanks goes to Lord Alika for the excessive work that he has done for me. Below is the email address in situation you are undergoing a heart break, and I assure you that as he has done mine for me, she will definitely help you too. lordalikaspelltemple@yahoo.co.uk or http://lordalikaspelltemp8.wix.com/http call him +2348072718865
Olivera
2016-04-10 06:04:02 +0200
I became HIV-positive in 2015, while I was working in Africa. I'm a health professional, but like most of the 20 million positive women worldwide, I was infected by my long-term regular partner. The challenge for every positive person is to take back control of their lives, in "Living Positively" with the virus. I'd always believed that good health was never maintained only by taking medication. More than ever, HIV reinforced for me that health is not just physical health, but also mental, emotional and spiritual well-being. An important part of the healing process for me is to be active in HIV/AIDS education, support and advocacy. I volunteer in a number of HIV/AIDS organizations, and in particular Positive Women, because the impact of HIV /AIDS on women is very different than from men. As once a positive person, I will forever be grateful to God Almighty and Doctor Osorba to reach me when i thought it is all over, Today am happy with my family living free after the medical doctor have confirmed my HIV status Negative, I have never in my life believed that HIV could be cure by any herbal medicine, I want to make sure that HIV never happens to anyone else. We can't prevent HIV by punishment, by stigma and discrimination. It's only through building a safe, supportive and caring environment, that positive people still have hope and they should contact Dr Osorba with this email: osorbaherbalhome@gmail.com so they can once again be visible in our community, to educate and advocate, to take better care of ourselves and our families. We're someone's daughter, partner, mother, grandmother, sister, aunt. When we get HIV, it impacts on our families too contact him today and leave carefree osorbaherbalhome@gmail.com Good luck.
Guest
2016-04-03 03:33:21 +0200
My name is Monica Brown, and I base in USA...My life is back!!! After 1 years of Broken marriage, my husband left me with two kids . I felt like my life was about to end i almost committed suicide, i was emotionally down for a very long time. Thanks to a spell caster called Dr Mohammed, which i met online. On one faithful day, as I was browsing through the internet,I came across allot of testimonies about this particular spell caster. Some people testified that he brought their Ex lover back, some testified that he restores womb,cure cancer,and other sickness, some testified that he can cast a spell to stop divorce and so on. i also come across one particular testimony,it was about a woman called Sonia,she testified about how he brought back her Ex lover in less than 2 days, and at the end of her testimony she dropped Dr Mohammed's e-mail address. After reading all these,I decided to give it a try. I contacted him via email and explained my problem to him. In just 48hours, my husband came back to me. We solved our issues, and we are even happier than before Dr Mohammed, is really a gifted man and i will not stop publishing him because he is a wonderful man... If you have a problem and you are looking for a real and genuine spell caster to solve all your problems for you. Try High monicaspiritualtemple@gmail.com anytime, he might be the answer to your problems. Here's his contact: monicaspiritualtemple@gmail.com or call him +2348134493948
Guest
2016-04-03 02:08:33 +0200
'After being in relationship with Wilson for seven years,he broke up with me, I did everything possible to bring him back but all was in vain, I wanted him back so much because of the love I have for him, I begged him with everything, I made promises but he refused. I explained my problem to someone online and she suggested that I should contact a spell caster that could help me cast a spell to bring him back but I am the type that don't believed in spell, I had no choice than to try it, I meant a spell caster called Dr Zuma zuk and I email him, and he told me there was no problem that everything will be okay before three days, that my ex will return to me before three days, he cast the spell and surprisingly in the second day, it was around 4pm. My ex called me, I was so surprised, I answered the call and all he said was that he was so sorry for everything that happened, that he wanted me to return to him, that he loves me so much. I was so happy and went to him, that was how we started living together happily again. Since then, I have made promise that anybody I know that have a relationship problem, I would be of help to such person by referring him or her to the only real and powerful spell caster who helped me with my own problem and who is different from all the fake ones out there. Anybody could need the help of the spell caster, his email: spiritualherbalisthealing@gmail.com or call him +2349055637784 you can email him if you need his assistance in your relationship or anything. CONTACT HIM NOW FOR SOLUTION TO ALL YOUR PROBLEMS'