Login Register Cart 0
Generic placeholder image

Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Pathophysiology, Current Therapeutic Options, Vaccine Candidates, and Drug Targets for Human Brucellosis

Author(s): Manisha Pritam and Rajnish Kumar*

Volume 17, 2024

Published on: 13 July, 2023

Article ID: e130723218680 Pages: 9

DOI: 10.2174/1874467217666230713093802

open_access

Abstract

Brucellosis is an infectious disease caused by different species of Brucella bacteria. It is also known as Malta fever, one of the neglected diseases that can cause infection in both animals and humans. Although human-to-human infection is rare, it can spread through the inhalation of airborne agents, and if left untreated, it can lead to serious health complications. In this review, we aim to highlight the pathophysiology, prevention, epidemiology, mitigation, cure, targets for drug development, and vaccine development against human brucellosis. Human brucellosis is mainly caused by consuming unpasteurized milk or dairy products, uncooked meat, and contact with infected animals. Human brucellosis outbreaks are mainly associated with developing and low- to middle-income countries. Brucella is present all over the world, and only some of the regions are at high risk, including Asia, Africa, Eastern Europe, Mexico, South and Central America, the Caribbean, the Mediterranean Basin, and the Middle East. Because of intracellular survival, inhibition of apoptosis, and immune evasion, Brucella can survive and multiply inside the host cell, which can cause chronic disease. By using proteomics approaches, several new drug targets were reported for human brucellosis that can be used for the development of novel drugs. We can also develop an efficient vaccine against human brucellosis by exploring previously reported vaccine candidates against animal brucellosis. The information provided through this review will facilitate research to control and cure human brucellosis and its complicated symptoms.

Keywords: Brucellosis, Drug target, Pathophysiology, Vaccine candidate, Inhibition of apoptosis, Rose Bengal test (RBT).

[1]
Smith, J.A. Brucella Lipopolysaccharide and pathogenicity: The core of the matter. Virulence, 2018, 9(1), 379-382.
[http://dx.doi.org/10.1080/21505594.2017.1395544] [PMID: 29144201]
[2]
Kim, H.N.; Hur, M.; Moon, H.W.; Shim, H.S.; Kim, H.; Ji, M.; Yun, Y.M.; Kim, S.Y.; Um, J.; Lee, Y.S.; Hwang, S.D. First case of human brucellosis caused by Brucella melitensis in Korea. Ann. Lab. Med., 2016, 36(4), 390-392.
[http://dx.doi.org/10.3343/alm.2016.36.4.390] [PMID: 27139618]
[3]
Avila-Granados, L.M.; Garcia-Gonzalez, D.G.; Zambrano-Varon, J.L.; Arenas-Gamboa, A.M. Brucellosis in colombia: Current status and challenges in the control of an endemic disease. Front. Vet. Sci., 2019, 6, 321.
[http://dx.doi.org/10.3389/fvets.2019.00321] [PMID: 31616678]
[4]
Corbel, M.J. Brucellosis in humans and animals.World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and World Organisation for Animal Health (OIE); Geneva, 2006, pp. 44-61.
[5]
Gharebaghi, N.; Sedokani, A.; Mehrno, M. A rare case of brucellosis with dermatomal pattern of cutaneous manifestation. Int. Med. Case Rep. J., 2019, 12, 223-228.
[http://dx.doi.org/10.2147/IMCRJ.S203682] [PMID: 31372063]
[6]
Hasanjani Roushan, M.R.; Ebrahimpour, S. Human brucellosis: An overview. Caspian J. Intern. Med., 2015, 6(1), 46-47.
[PMID: 26221498]
[7]
Ariza, J.; Servitje, O.; Pallarés, R.; Fernández Viladrich, P.; Rufí, G.; Peyrí, J.; Gudiol, F. Characteristic cutaneous lesions in patients with brucellosis. Arch. Dermatol., 1989, 125(3), 380-383.
[http://dx.doi.org/10.1001/archderm.1989.01670150070010] [PMID: 2923445]
[8]
Korkmaz, P.; Doyuk Kartal, E. Skin manifestations associated with brucellosis. EMJ Dermatol, 2016, 119-125.
[http://dx.doi.org/10.33590/emjdermatol/10312753]
[9]
Elbehiry, A.; Aldubaib, M.; Marzouk, E.; Abalkhail, A.; Almuzaini, A.M.; Rawway, M.; Alghamdi, A.; Alqarni, A.; Aldawsari, M.; Draz, A. The development of diagnostic and vaccine strategies for early detection and control of human brucellosis, particularly in endemic areas. Vaccines, 2023, 11(3), 654.
[http://dx.doi.org/10.3390/vaccines11030654] [PMID: 36992237]
[10]
Yagupsky, P.; Morata, P.; Colmenero, J.D. Laboratory diagnosis of human brucellosis. Clin. Microbiol. Rev., 2019, 33(1), e00073-19.
[http://dx.doi.org/10.1128/CMR.00073-19] [PMID: 31722888]
[11]
Li, X.; Sun, X.; Zhang, Y.; Luo, S.X.; Yin, H.; Zhang, H.; Wang, Z.; Cheng, Z. Human descending aorta injury caused by brucellosis: A case report. Medicine, 2023, 102(19), e33764.
[http://dx.doi.org/10.1097/MD.0000000000033764] [PMID: 37171302]
[12]
Willems, S.A.; Brouwers, J.J.W.M.; Eefting, D. Aortic and iliac involvement in brucellosis : A rare but life threatening manifestation: A review of the literature. Eur. J. Vasc. Endovasc. Surg., 2022, 63(5), 743-750.
[http://dx.doi.org/10.1016/j.ejvs.2022.02.004] [PMID: 35282998]
[13]
Castaño, M.J.; Solera, J. Chronic brucellosis and persistence of brucella melitensis DNA. J. Clin. Microbiol., 2009, 47(7), 2084-2089.
[http://dx.doi.org/10.1128/JCM.02159-08] [PMID: 19420176]
[14]
González-Espinoza, G.; Arce-Gorvel, V.; Mémet, S.; Gorvel, J.P. Brucella: Reservoirs and niches in animals and humans. Pathogens, 2021, 10(2), 186.
[http://dx.doi.org/10.3390/pathogens10020186] [PMID: 33572264]
[15]
Centers for disease control and prevention, brucellosis cdc yellow book 2024, travel-associated infections & diseases. 2023. Avaialble from:https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/
[16]
Dean, A.S.; Crump, L.; Greter, H.; Schelling, E.; Zinsstag, J. Global burden of human brucellosis: A systematic review of disease frequency. PLoS Negl. Trop. Dis., 2012, 6(10), e1865.
[http://dx.doi.org/10.1371/journal.pntd.0001865] [PMID: 23145195]
[17]
Centers for disease control and prevention. 2012. Avaialble from:https://www.cdc.gov/brucellosis/exposure/areas.html
[18]
Lai, S.; Zhou, H.; Xiong, W.; Gilbert, M.; Huang, Z.; Yu, J.; Yin, W.; Wang, L.; Chen, Q.; Li, Y.; Mu, D.; Zeng, L.; Ren, X.; Geng, M.; Zhang, Z.; Cui, B.; Li, T.; Wang, D.; Li, Z.; Wardrop, N.A.; Tatem, A.J.; Yu, H. Changing epidemiology of human brucellosis, China, 1955–2014. Emerg. Infect. Dis., 2017, 23(2), 184-194.
[http://dx.doi.org/10.3201/eid2302.151710] [PMID: 28098531]
[19]
European Centre for Disease Prevention and Control. Brucellosis. In: ECDC. Annual epidemiological report for 2019. Stockholm: ECDC. 2022. Avaialble from: https://www.ecdc.europa.eu/sites/default/files/documents/BRUC_AER_2019.pdf
[20]
Parai, D.; Sahoo, S.K.; Pattnaik, M.; Swain, A.; Peter, A.; Samanta, L.J.; Pradhan, R.; Choudhary, H.R.; Nahak, K.C.; Pati, S.; Bhattacharya, D. Seroprevalence of human brucellosis among the tribal and non-tribal population residing in an eastern state of India: Findings from the state-wide serosurvey. Front. Microbiol., 2022, 13, 1070276.
[http://dx.doi.org/10.3389/fmicb.2022.1070276] [PMID: 36519171]
[21]
Kothalawala, K.A.C.; Makita, K.; Kothalawala, H.; Jiffry, A.M.; Kubota, S.; Kono, H. Association of farmers’ socio-economics with bovine brucellosis epidemiology in the dry zone of Sri Lanka. Prev. Vet. Med., 2017, 147, 117-123.
[http://dx.doi.org/10.1016/j.prevetmed.2017.08.014] [PMID: 29254709]
[22]
Franc, K.A.; Krecek, R.C.; Häsler, B.N.; Arenas-Gamboa, A.M. Brucellosis remains a neglected disease in the developing world: A call for interdisciplinary action. BMC Public Health, 2018, 18(1), 125.
[http://dx.doi.org/10.1186/s12889-017-5016-y] [PMID: 29325516]
[23]
Giambartolomei, G.H.; Delpino, M.V. Immunopathogenesis of hepatic brucellosis. Front. Cell. Infect. Microbiol., 2019, 9, 423.
[http://dx.doi.org/10.3389/fcimb.2019.00423] [PMID: 31956605]
[24]
Martirosyan, A.; Moreno, E.; Gorvel, J.P. An evolutionary strategy for a stealthy intracellular Brucella pathogen. Immunol. Rev., 2011, 240(1), 211-234.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00982.x] [PMID: 21349096]
[25]
Grilló, M.J.; Blasco, J.M.; Gorvel, J.P.; Moriyón, I.; Moreno, E. What have we learned from brucellosis in the mouse model? Vet. Res., 2012, 43(1), 29.
[http://dx.doi.org/10.1186/1297-9716-43-29] [PMID: 22500859]
[26]
López-Santiago, R.; Sánchez-Argáez, A.B.; De Alba-Núñez, L.G.; Baltierra-Uribe, S.L.; Moreno-Lafont, M.C. Immune response to mucosal Brucella Infection. Front. Immunol., 2019, 10, 1759.
[http://dx.doi.org/10.3389/fimmu.2019.01759] [PMID: 31481953]
[27]
Guzmán-Verri, C.; González-Barrientos, R.; Hernández-Mora, G.; Morales, J.A.; Baquero-Calvo, E.; Chaves-Olarte, E.; Moreno, E. Brucella ceti and brucellosis in cetaceans. Front. Cell. Infect. Microbiol., 2012, 2, 3.
[http://dx.doi.org/10.3389/fcimb.2012.00003] [PMID: 22919595]
[28]
Celli, J. The intracellular life cycle of Brucella spp. Microbiol. Spectr., 2019, 7(2), 7.2.07.
[http://dx.doi.org/10.1128/microbiolspec.BAI-0006-2019] [PMID: 30848234]
[29]
Starr, T.; Ng, T.W.; Wehrly, T.D.; Knodler, L.A.; Celli, J. Brucella intracellular replication requires trafficking through the late endosomal/lysosomal compartment. Traffic, 2008, 9(5), 678-694.
[http://dx.doi.org/10.1111/j.1600-0854.2008.00718.x] [PMID: 18266913]
[30]
von Bargen, K.; Gorvel, J.P.; Salcedo, S.P. Internal affairs: Investigating the Brucella intracellular lifestyle. FEMS Microbiol. Rev., 2012, 36(3), 533-562.
[http://dx.doi.org/10.1111/j.1574-6976.2012.00334.x] [PMID: 22373010]
[31]
Porte, F.; Naroeni, A.; Ouahrani-Bettache, S.; Liautard, J.P. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect. Immun., 2003, 71(3), 1481-1490.
[http://dx.doi.org/10.1128/IAI.71.3.1481-1490.2003] [PMID: 12595466]
[32]
Haag, A.F.; Myka, K.K.; Arnold, M.F.F.; Caro-Hernández, P.; Ferguson, G.P. Importance of Lipopolysaccharide and Cyclic β -1,2-Glucans in Brucella -Mammalian Infections. Int. J. Microbiol., 2010, 2010, 1-12.
[http://dx.doi.org/10.1155/2010/124509] [PMID: 21151694]
[33]
Ahmed, W.; Zheng, K.; Liu, Z.F. Establishment of chronic infection: Brucella’s stealth strategy. Front. Cell. Infect. Microbiol., 2016, 6(30), 30.
[http://dx.doi.org/10.3389/fcimb.2016.00030] [PMID: 27014640]
[34]
Zhang, G.; Liang, C.; Liu, C.; Zhang, J.; Pi, X.; Zhang, Y.; Liang, X.; Wang, L.; Zheng, B. Whole-genome sequence of brucella melitensis strain b7, isolated from a blood sample of a brucellosis patient from hulunbuir, inner mongolia, China. Microbiol. Resour. Announc., 2019, 8(24), e00119-19.
[http://dx.doi.org/10.1128/MRA.00119-19] [PMID: 31196914]
[35]
Pei, J.; Kahl-McDonagh, M.; Ficht, T.A. Brucella dissociation is essential for macrophage egress and bacterial dissemination. Front. Cell. Infect. Microbiol., 2014, 4, 23.
[http://dx.doi.org/10.3389/fcimb.2014.00023] [PMID: 24634889]
[36]
Hop, H.T.; Arayan, L.T.; Huy, T.X.N.; Reyes, A.W.B.; Vu, S.H.; Min, W.; Lee, H.J.; Rhee, M.H.; Chang, H.H.; Kim, S. The Key role of c-Fos for immune regulation and bacterial dissemination in brucella infected macrophage. Front. Cell. Infect. Microbiol., 2018, 8, 287.
[http://dx.doi.org/10.3389/fcimb.2018.00287] [PMID: 30186773]
[37]
Alavi, S.M.; Alavi, L. Treatment of brucellosis: A systematic review of studies in recent twenty years. Caspian J. Intern. Med., 2013, 4(2), 636-641.
[PMID: 24009951]
[38]
Skalsky, K.; Yahav, D.; Bishara, J.; Pitlik, S.; Leibovici, L.; Paul, M. Treatment of human brucellosis: Systematic review and meta-analysis of randomised controlled trials. BMJ, 2008, 336(7646), 701-704.
[http://dx.doi.org/10.1136/bmj.39497.500903.25] [PMID: 18321957]
[39]
Perkins, S.D.; Smither, S.J.; Atkins, H.S. Towards a Brucella vaccine for humans. FEMS Microbiol. Rev., 2010, 34(3), 379-394.
[http://dx.doi.org/10.1111/j.1574-6976.2010.00211.x] [PMID: 20180858]
[40]
Chacón-Díaz, C.; Altamirano-Silva, P.; González-Espinoza, G.; Medina, M.C.; Alfaro-Alarcón, A.; Bouza-Mora, L.; Jiménez-Rojas, C.; Wong, M.; Barquero-Calvo, E.; Rojas, N.; Guzmán-Verri, C.; Moreno, E.; Chaves-Olarte, E. Brucella canis is an intracellular pathogen that induces a lower proinflammatory response than smooth zoonotic counterparts. Infect. Immun., 2015, 83(12), 4861-4870.
[http://dx.doi.org/10.1128/IAI.00995-15] [PMID: 26438796]
[41]
Gheibi, A.; Khanahmad, H.; Kashfi, K.; Sarmadi, M.; Khorramizadeh, M.R. Development of new generation of vaccines for Brucella abortus. Heliyon, 2018, 4(12), e01079.
[http://dx.doi.org/10.1016/j.heliyon.2018.e01079] [PMID: 30603712]
[42]
Dabral, N.; Burcham, G.N.; Jain-Gupta, N.; Sriranganathan, N.; Vemulapalli, R. Overexpression of wbkF gene in Brucella abortus RB51WboA leads to increased O-polysaccharide expression and enhanced vaccine efficacy against B. abortus 2308, B. melitensis 16M, and B. suis 1330 in a murine brucellosis model. PLoS One, 2019, 14(3), e0213587.
[http://dx.doi.org/10.1371/journal.pone.0213587] [PMID: 30856219]
[43]
O’Callaghan, D. Human brucellosis: Recent advances and future challenges. Infect. Dis. Poverty, 2020, 9(1), 101.
[http://dx.doi.org/10.1186/s40249-020-00715-1] [PMID: 32703319]
[44]
Avila-Calderón, E.D.; Lopez-Merino, A.; Sriranganathan, N.; Boyle, S.M.; Contreras-Rodríguez, A. A history of the development of Brucella vaccines. BioMed Res. Int., 2013, 2013, 1-8.
[http://dx.doi.org/10.1155/2013/743509] [PMID: 23862154]
[45]
Lalsiamthara, J.; Lee, J.H. Development and trial of vaccines against Brucella. J. Vet. Sci., 2017, 18(S1), 281-290.
[http://dx.doi.org/10.4142/jvs.2017.18.S1.281] [PMID: 28859268]
[46]
Pritam, M.; Singh, G.; Swaroop, S.; Singh, A.K.; Pandey, B.; Singh, S.P. A cutting-edge immunoinformatics approach for design of multi-epitope oral vaccine against dreadful human malaria. Int. J. Biol. Macromol., 2020, 158, 159-179.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.04.191] [PMID: 32360460]
[47]
Kumar, R.; Srivastava, J.K.; Singh, R.; Siddiqui, M.H.; Mansouri, R.A.; Abdulhakim, J.A.; Bin-Jumah, M.N.; Alkahtani, S.; Abdel-Daim, M.M.; Uddin, M.S. Available compounds with therapeutic potential against COVID-19: Antimicrobial therapies, supportive care, and probable vaccines. Front. Pharmacol., 2020, 11, 582025.
[http://dx.doi.org/10.3389/fphar.2020.582025] [PMID: 33123014]
[48]
Khurana, S.K.; Sehrawat, A.; Tiwari, R.; Prasad, M.; Gulati, B.; Shabbir, M.Z.; Chhabra, R.; Karthik, K.; Patel, S.K.; Pathak, M.; Iqbal Yatoo, M.; Gupta, V.K.; Dhama, K.; Sah, R.; Chaicumpa, W. Bovine brucellosis : A comprehensive review. Vet. Q., 2021, 41(1), 61-88.
[http://dx.doi.org/10.1080/01652176.2020.1868616] [PMID: 33353489]
[49]
Hans, R.; Yadav, P.K.; Sharma, P.K.; Boopathi, M.; Thavaselvam, D. Development and validation of immunoassay for whole cell detection of Brucella abortus and Brucella melitensis. Sci. Rep., 2020, 10(1), 8543.
[http://dx.doi.org/10.1038/s41598-020-65347-9] [PMID: 32444793]
[50]
Li, Z.; Wang, X.; Zhu, X.; Wang, M.; Cheng, H.; Li, D.; Liu, Z.G. Molecular characteristics of brucella isolates collected from humans in hainan province, china. Front. Microbiol., 2020, 11, 452.
[http://dx.doi.org/10.3389/fmicb.2020.00452] [PMID: 32292391]
[51]
Yin, D.; Li, L.; Song, X.; Li, H.; Wang, J.; Ju, W.; Qu, X.; Song, D.; Liu, Y.; Meng, X.; Cao, H.; Song, W.; Meng, R.; Liu, J.; Li, J.; Xu, K. A novel multi-epitope recombined protein for diagnosis of human brucellosis. BMC Infect. Dis., 2016, 16(1), 219.
[http://dx.doi.org/10.1186/s12879-016-1552-9] [PMID: 27206475]
[52]
Herrou, J.; Willett, J.W.; Fiebig, A.; Czyż, D.M.; Cheng, J.X.; Ultee, E.; Briegel, A.; Bigelow, L.; Babnigg, G.; Kim, Y.; Crosson, S. Brucella periplasmic protein EipB Is a molecular determinant of cell envelope integrity and virulence. J. Bacteriol., 2019, 201(12), e00134-19.
[http://dx.doi.org/10.1128/JB.00134-19] [PMID: 30936371]
[53]
Kahl-McDonagh, M.M.; Elzer, P.H.; Hagius, S.D.; Walker, J.V.; Perry, Q.L.; Seabury, C.M.; den Hartigh, A.B.; Tsolis, R.M.; Adams, L.G.; Davis, D.S.; Ficht, T.A. Evaluation of novel Brucella melitensis unmarked deletion mutants for safety and efficacy in the goat model of brucellosis. Vaccine, 2006, 24(24), 5169-5177.
[http://dx.doi.org/10.1016/j.vaccine.2006.04.005] [PMID: 16697090]
[54]
Arenas-Gamboa, A.M.; Rice-Ficht, A.C.; Fan, Y.; Kahl-McDonagh, M.M.; Ficht, T.A. Extended safety and efficacy studies of the attenuated Brucella vaccine candidates 16 M(Delta)vjbR and S19(Delta)vjbR in the immunocompromised IRF-1-/- mouse model. Clin. Vaccine Immunol., 2012, 19(2), 249-260.
[http://dx.doi.org/10.1128/CVI.05321-11] [PMID: 22169089]
[55]
Palmer, M.V.; Olsen, S.C.; Cheville, N.F. Safety and immunogenicity of Brucella abortus strain RB51 vaccine in pregnant cattle. Am. J. Vet. Res., 1997, 58(5), 472-477.
[PMID: 9140553]
[56]
Ponsart, C.; Riou, M.; Locatelli, Y.; Jacques, I.; Fadeau, A.; Jay, M.; Simon, R.; Perrot, L.; Freddi, L.; Breton, S.; Chaumeil, T.; Blanc, B.; Ortiz, K.; Vion, C.; Rioult, D.; Quéméré, E.; Sarradin, P.; Chollet, J.Y.; Garin-Bastuji, B.; Rossi, S. Brucella melitensis Rev.1 vaccination generates a higher shedding risk of the vaccine strain in Alpine ibex (Capra ibex) compared to the domestic goat (Capra hircus). Vet. Res., 2019, 50(1), 100.
[http://dx.doi.org/10.1186/s13567-019-0717-0] [PMID: 31775863]
[57]
Gupta, S.; Singh, D.; Gupta, M.; Bhatnagar, R. A combined subunit vaccine comprising BP26, Omp25 and L7/L12 against brucellosis. Pathog. Dis., 2019, 77(8), ftaa002.
[http://dx.doi.org/10.1093/femspd/ftaa002] [PMID: 31971564]
[58]
Cherwonogrodzky, J.W.; Barabé, N.D.; Grigat, M.L.; Lee, W.E.; Poirier, R.T.; Jager, S.J.; Berger, B.J. Thermostable cross-protective subunit vaccine against Brucella species. Clin. Vaccine Immunol., 2014, 21(12), 1681-1688.
[http://dx.doi.org/10.1128/CVI.00447-14] [PMID: 25320267]
[59]
Khademvatan, S.; Saki, J.; Khajeddin, N.; Izadi-Mazidi, M.; Beladi, R.; Shafiee, B.; Salehi, Z. Toxoplasma gondii Exposure and the Risk of Schizophrenia. Jundishapur J. Microbiol., 2014, 7(11), e12776.
[http://dx.doi.org/10.5812/jjm.18789] [PMID: 25774275]
[60]
Zhu, L.; Wang, Q.; Wang, Y.; Xu, Y.; Peng, D.; Huang, H.; Hu, L.; Wei, K.; Zhu, R. Comparison of immune effects between Brucella recombinant Omp10-Omp28-L7/L12 proteins expressed in eukaryotic and prokaryotic systems. Front. Vet. Sci., 2020, 7, 576.
[http://dx.doi.org/10.3389/fvets.2020.00576] [PMID: 33195494]
[61]
Cassataro, J.; Velikovsky, C.A.; de la Barrera, S.; Estein, S.M.; Bruno, L.; Bowden, R.; Pasquevich, K.A.; Fossati, C.A.; Giambartolomei, G.H. A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infect. Immun., 2005, 73(10), 6537-6546.
[http://dx.doi.org/10.1128/IAI.73.10.6537-6546.2005] [PMID: 16177328]
[62]
Velikovsky, C.A.; Goldbaum, F.A.; Cassataro, J.; Estein, S.; Bowden, R.A.; Bruno, L.; Fossati, C.A.; Giambartolomei, G.H. Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used. Infect. Immun., 2003, 71(10), 5750-5755.
[http://dx.doi.org/10.1128/IAI.71.10.5750-5755.2003] [PMID: 14500496]
[63]
Pasquevich, K.A.; Estein, S.M.; Samartino, C.G.; Zwerdling, A.; Coria, L.M.; Barrionuevo, P.; Fossati, C.A.; Giambartolomei, G.H.; Cassataro, J. Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection. Infect. Immun., 2009, 77(1), 436-445.
[http://dx.doi.org/10.1128/IAI.01151-08] [PMID: 18981242]
[64]
Al-Mariri, A.; Tibor, A.; Mertens, P.; De Bolle, X.; Michel, P.; Godefroid, J.; Walravens, K.; Letesson, J.J. Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant. Infect. Immun., 2001, 69(8), 4816-4822.
[http://dx.doi.org/10.1128/IAI.69.8.4816-4822.2001] [PMID: 11447155]
[65]
Delpino, M.V.; Marchesini, M.I.; Estein, S.M.; Comerci, D.J.; Cassataro, J.; Fossati, C.A.; Baldi, P.C. A bile salt hydrolase of Brucella abortus contributes to the establishment of a successful infection through the oral route in mice. Infect. Immun., 2007, 75(1), 299-305.
[http://dx.doi.org/10.1128/IAI.00952-06] [PMID: 17088355]
[66]
Gómez, L.; Llanos, J.; Escalona, E.; Sáez, D.; Álvarez, F.; Molina, R.; Flores, M.; Oñate, A. Multivalent Fusion DNA Vaccine against Brucella abortus. BioMed Res. Int., 2017, 2017, 1-8.
[http://dx.doi.org/10.1155/2017/6535479]
[67]
Bugybayeva, D.; Kydyrbayev, Z.; Zinina, N.; Assanzhanova, N.; Yespembetov, B.; Kozhamkulov, Y.; Zakarya, K.; Ryskeldinova, S.; Tabynov, K. A new candidate vaccine for human brucellosis based on influenza viral vectors: A preliminary investigation for the development of an immunization schedule in a guinea pig model. Infect. Dis. Poverty, 2021, 10(1), 13.
[http://dx.doi.org/10.1186/s40249-021-00801-y] [PMID: 33593447]
[68]
Yang, X.; Hudson, M.; Walters, N.; Bargatze, R.F.; Pascual, D.W. Selection of protective epitopes for Brucella melitensis by DNA vaccination. Infect. Immun., 2005, 73(11), 7297-7303.
[http://dx.doi.org/10.1128/IAI.73.11.7297-7303.2005] [PMID: 16239526]
[69]
Oñate, A.A.; Céspedes, S.; Cabrera, A.; Rivers, R.; González, A.; Muñoz, C.; Folch, H.; Andrews, E. A DNA vaccine encoding Cu,Zn superoxide dismutase of Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun., 2003, 71(9), 4857-4861.
[http://dx.doi.org/10.1128/IAI.71.9.4857-4861.2003] [PMID: 12933826]
[70]
Commander, N.J.; Spencer, S.A.; Wren, B.W.; MacMillan, A.P. The identification of two protective DNA vaccines from a panel of five plasmid constructs encoding Brucella melitensis 16M genes. Vaccine, 2007, 25(1), 43-54.
[http://dx.doi.org/10.1016/j.vaccine.2006.07.046] [PMID: 17049676]
[71]
Sadeghi, Z.; Fasihi-Ramandi, M.; Bouzari, S. Evaluation of immunogenicity of novel multi-epitope subunit vaccines in combination with poly I:C against Brucella melitensis and Brucella abortus infection. Int. Immunopharmacol., 2019, 75(105829), 105829.
[http://dx.doi.org/10.1016/j.intimp.2019.105829] [PMID: 31437796]
[72]
Vizcaíno, N.; Cloeckaert, A.; Dubray, G.; Zygmunt, M.S. Cloning, nucleotide sequence, and expression of the gene coding for a ribosome releasing factor-homologous protein of Brucella melitensis. Infect. Immun., 1996, 64(11), 4834-4837.
[http://dx.doi.org/10.1128/iai.64.11.4834-4837.1996] [PMID: 8890247]
[73]
Mahmud, A.; Khan, M.T.; Iqbal, A. Identification of novel drug targets for humans and potential vaccine targets for cattle by subtractive genomic analysis of Brucella abortus strain 2308. Microb. Pathog., 2019, 137(103731), 103731.
[http://dx.doi.org/10.1016/j.micpath.2019.103731] [PMID: 31509762]
[74]
Rahman, N.; Shah, M.; Muhammad, I.; Khan, H.; Imran, M. Genome-wide core proteome analysis of brucella melitensis strains for potential drug target prediction. Mini Rev. Med. Chem., 2021, 21(18), 2778-2787.
[http://dx.doi.org/10.2174/1389557520666200707133347] [PMID: 32634082]
[75]
Ojo, K.K.; Ranade, R.M.; Zhang, Z.; Dranow, D.M.; Myers, J.B.; Choi, R.; Nakazawa Hewitt, S.; Edwards, T.E.; Davies, D.R.; Lorimer, D.; Boyle, S.M.; Barrett, L.K.; Buckner, F.S.; Fan, E.; Van Voorhis, W.C. Brucella melitensis methionyl-trna-synthetase (metrs), a potential drug target for brucellosis. PLoS One, 2016, 11(8), e0160350.
[http://dx.doi.org/10.1371/journal.pone.0160350] [PMID: 27500735]
[76]
Pradeepkiran, J.A.; konidala, K.; Yellapu, N.; Bhaskar, M. Modeling, molecular dynamics, and docking assessment of transcription factor rho: A potential drug target in Brucella melitensis 16M. Drug Des. Devel. Ther., 2015, 9, 1897-1912.
[http://dx.doi.org/10.2147/DDDT.S77020] [PMID: 25848225]
[77]
Then, R. Dihydropteroate synthase. xpharm. Comprehensive Pharmacology Reference, Elsevier., 2007, 2017, 1-7.
[78]
Raimondi, M.; Randazzo, O.; La Franca, M.; Barone, G.; Vignoni, E.; Rossi, D.; Collina, S. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules, 2019, 24(6), 1140.
[http://dx.doi.org/10.3390/molecules24061140] [PMID: 30909399]
[79]
Paradis-Bleau, C.; Lloyd, A.; Sanschagrin, F.; Clarke, T.; Blewett, A.; Bugg, T.D.H.; Levesque, R.C. Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF. BMC Biochem., 2008, 9(1), 33.
[http://dx.doi.org/10.1186/1471-2091-9-33] [PMID: 19099588]
[80]
Amera, G.M.; Khan, R.J.; Jha, R.K.; Pathak, A.; Muthukumaran, J.; Singh, A.K. Prioritization of Mur family drug targets against A. baumannii and identification of their homologous proteins through molecular phylogeny, primary sequence, and structural analysis. J. Genet. Eng. Biotechnol., 2020, 18(1), 33.
[http://dx.doi.org/10.1186/s43141-020-00048-4] [PMID: 32725318]
[81]
Salmon-Divon, M.; Yeheskel, A.; Kornspan, D. Genomic analysis of the original Elberg Brucella melitensis Rev.1 vaccine strain reveals insights into virulence attenuation. Virulence, 2018, 9(1), 1436-1448.
[http://dx.doi.org/10.1080/21505594.2018.1511677] [PMID: 30139304]
[82]
Chang, C.M.; Chern, J.; Chen, M.Y.; Huang, K.F.; Chen, C.H.; Yang, Y.L.; Wu, S.H. Avenaciolides: Potential mura-targeted inhibitors against peptidoglycan biosynthesis in methicillin-resistant staphylococcus aureus (MRSA). J. Am. Chem. Soc., 2015, 137(1), 267-275.
[http://dx.doi.org/10.1021/ja510375f] [PMID: 25521652]
[83]
Zhang, F.; Graham, J.; Zhai, T.; Liu, Y.; Huang, Z. Discovery of mura inhibitors as novel antimicrobials through an integrated computational and experimental approach. Antibiotics, 2022, 11(4), 528.
[http://dx.doi.org/10.3390/antibiotics11040528] [PMID: 35453279]
[84]
Rani, J.; Silla, Y.; Borah, K.; Ramachandran, S.; Bajpai, U. Repurposing of FDA-approved drugs to target MurB and MurE enzymes in Mycobacterium tuberculosis. J. Biomol. Struct. Dyn., 2020, 38(9), 2521-2532.
[http://dx.doi.org/10.1080/07391102.2019.1637280] [PMID: 31244382]
[85]
Ashraf, B.; Atiq, N.; Khan, K.; Wadood, A.; Uddin, R. Subtractive genomics profiling for potential drug targets identification against moraxella catarrhalis. PLoS One, 2022, 17(8), e0273252.
[http://dx.doi.org/10.1371/journal.pone.0273252] [PMID: 36006987]
[86]
Chhabra, G.; Dixit, A.; Garg, L.C. DNA polymerase III a subunit from Mycobacterium tuberculosis H37Rv: Homology modeling and molecular docking of its inhibitor. Bioinformation, 2011, 6(2), 69-73.
[http://dx.doi.org/10.6026/97320630006069] [PMID: 21544168]
[87]
Tarantino, P.M., Jr; Zhi, C.; Wright, G.E.; Brown, N.C. Inhibitors of DNA polymerase III as novel antimicrobial agents against gram-positive eubacteria. Antimicrob. Agents Chemother., 1999, 43(8), 1982-1987.
[http://dx.doi.org/10.1128/AAC.43.8.1982] [PMID: 10428923]
[88]
Aiello, D.; Barnes, M.H.; Biswas, E.E.; Biswas, S.B.; Gu, S.; Williams, J.D.; Bowlin, T.L.; Moir, D.T. Discovery, characterization and comparison of inhibitors of bacillus anthracis and staphylococcus aureus replicative DNA helicases. Bioorg. Med. Chem., 2009, 17(13), 4466-4476.
[http://dx.doi.org/10.1016/j.bmc.2009.05.014] [PMID: 19477652]
[89]
Ma, C.; Yang, X.; Lewis, P.J. Bacterial transcription as a target for antibacterial drug development. Microbiol. Mol. Biol. Rev., 2016, 80(1), 139-160.
[http://dx.doi.org/10.1128/MMBR.00055-15] [PMID: 26764017]
[90]
Mandell, Z.F.; Oshiro, R.T.; Yakhnin, A.V.; Vishwakarma, R.; Kashlev, M.; Kearns, D.B.; Babitzke, P.; Nus, G. NusG is an intrinsic transcription termination factor that stimulates motility and coordinates gene expression with NusA. eLife, 2021, 10, e61880.
[http://dx.doi.org/10.7554/eLife.61880] [PMID: 33835023]
[91]
O’Neill, A.J.; Huovinen, T.; Fishwick, C.W.G.; Chopra, I. Molecular genetic and structural modeling studies of staphylococcus aureus RNA polymerase and the fitness of rifampin resistance genotypes in relation to clinical prevalence. Antimicrob. Agents Chemother., 2006, 50(1), 298-309.
[http://dx.doi.org/10.1128/AAC.50.1.298-309.2006] [PMID: 16377701]
[92]
Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem 2023 update. Nucleic Acids Res., 2023, 51(D1), D1373-D1380.
[http://dx.doi.org/10.1093/nar/gkac956] [PMID: 36305812]
[93]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]

Rights & Permissions Print Cite
Article Metrics
75
5
2
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy