Natural Product Type III Secretion System Inhibitors

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2019 Sep 27

PMID 31554164

Citations 16

Authors

Heather A Pendergrass

Aaron E May

Affiliations

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Abstract

Many known inhibitors of the bacterial type III secretion system (T3SS), a virulence factor used by pathogenic bacteria to infect host cells, are natural products. These compounds, produced by bacteria, fungi, and plants, may have developed as prophylactic treatments for potential attack by bacterial pathogens or as an attempt by symbiotic organisms to protect their hosts. Regardless, better understanding of the structures and mechanisms of action of these compounds may open opportunities for drug development against diseases caused by pathogens utilizing the T3SS. This review will cover selected known natural products of the T3SS and detail what is known of their origin and mechanism of action. These inhibitors highlight nature's ability to modulate interactions between organisms at a cellular level.

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References

Yang J, Hocking D, Cheng C, Dogovski C, Perugini M, Holien J . Disarming bacterial virulence through chemical inhibition of the DNA binding domain of an AraC-like transcriptional activator protein. J Biol Chem. 2013; 288(43):31115-26. PMC: 3829424. DOI: 10.1074/jbc.M113.503912. View

Fasciano A, Shaban L, Mecsas J . Promises and Challenges of the Type Three Secretion System Injectisome as an Antivirulence Target. EcoSal Plus. 2019; 8(2). PMC: 6367940. DOI: 10.1128/ecosalplus.ESP-0032-2018. View

Zetterstrom C, Hasselgren J, Salin O, Davis R, Quinn R, Sundin C . The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. PLoS One. 2013; 8(12):e81969. PMC: 3853165. DOI: 10.1371/journal.pone.0081969. View

Croxen M, Finlay B . Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol. 2009; 8(1):26-38. DOI: 10.1038/nrmicro2265. View

Bzdzion L, Krezel H, Wrzeszcz K, Grzegorek I, Nowinska K, Chodaczek G . Design of small molecule inhibitors of type III secretion system ATPase EscN from enteropathogenic Escherichia coli. Acta Biochim Pol. 2016; 64(1):49-63. DOI: 10.18388/abp.2016_1265. View

Mondal A, Gandhi A, Fimognari C, Atanasov A, Bishayee A . Alkaloids for cancer prevention and therapy: Current progress and future perspectives. Eur J Pharmacol. 2019; 858:172472. DOI: 10.1016/j.ejphar.2019.172472. View

Park D, Lara-Tejero M, Waxham M, Li W, Hu B, Galan J . Visualization of the type III secretion mediated -host cell interface using cryo-electron tomography. Elife. 2018; 7. PMC: 6175578. DOI: 10.7554/eLife.39514. View

Bartra S, Lorica C, Qian L, Gong X, Bahnan W, Barreras Jr H . Chromosomally-Encoded Type III Secretion Effector Proteins Promote Infection in Cells and in Mice. Front Cell Infect Microbiol. 2019; 9:23. PMC: 6396649. DOI: 10.3389/fcimb.2019.00023. View

de Grado M, Abe A, Gauthier A, DeVinney R, Finlay B . Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli. Cell Microbiol. 2001; 1(1):7-17. DOI: 10.1046/j.1462-5822.1999.00001.x. View

10.

Cornelis G, Van Gijsegem F . Assembly and function of type III secretory systems. Annu Rev Microbiol. 2000; 54:735-74. DOI: 10.1146/annurev.micro.54.1.735. View

11.

Bohnhoff M, Miller C, Martin W . RESISTANCE OF THE MOUSE'S INTESTINAL TRACT TO EXPERIMENTAL SALMONELLA INFECTION. I. FACTORS WHICH INTERFERE WITH THE INITIATION OF INFECTION BY ORAL INOCULATION. J Exp Med. 1964; 120:805-16. PMC: 2137858. DOI: 10.1084/jem.120.5.805. View

12.

Andrade A, Pardo J, Espinosa N, Perez-Hernandez G, Gonzalez-Pedrajo B . Enzymatic characterization of the enteropathogenic Escherichia coli type III secretion ATPase EscN. Arch Biochem Biophys. 2007; 468(1):121-7. DOI: 10.1016/j.abb.2007.09.020. View

13.

Warawa J, Finlay B, Kenny B . Type III secretion-dependent hemolytic activity of enteropathogenic Escherichia coli. Infect Immun. 1999; 67(10):5538-40. PMC: 96921. DOI: 10.1128/IAI.67.10.5538-5540.1999. View

14.

Morgan J, Duncan M, Johnson K, Diepold A, Lam H, Dupzyk A . Piericidin A1 Blocks Ysc Type III Secretion System Needle Assembly. mSphere. 2017; 2(1). PMC: 5311113. DOI: 10.1128/mSphere.00030-17. View

15.

Elliott S, Sperandio V, Giron J, Shin S, Mellies J, Wainwright L . The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli. Infect Immun. 2000; 68(11):6115-26. PMC: 97688. DOI: 10.1128/IAI.68.11.6115-6126.2000. View

16.

Wang H, Avican K, Fahlgren A, Erttmann S, Nuss A, Dersch P . Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science. 2016; 353(6298):492-5. DOI: 10.1126/science.aaf7501. View

17.

Li J, Sun W, Guo Z, Lu C, Shen Y . Fusaric acid modulates Type Three Secretion System of Salmonella enterica serovar Typhimurium. Biochem Biophys Res Commun. 2014; 449(4):455-9. DOI: 10.1016/j.bbrc.2014.05.044. View

18.

Hauser A . The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol. 2009; 7(9):654-65. PMC: 2766515. DOI: 10.1038/nrmicro2199. View

19.

Loquet A, Sgourakis N, Gupta R, Giller K, Riedel D, Goosmann C . Atomic model of the type III secretion system needle. Nature. 2012; 486(7402):276-9. PMC: 3598588. DOI: 10.1038/nature11079. View

20.

Abe A, de Grado M, Pfuetzner R, DeVinney R, Puente J, Strynadka N . Enteropathogenic Escherichia coli translocated intimin receptor, Tir, requires a specific chaperone for stable secretion. Mol Microbiol. 1999; 33(6):1162-75. DOI: 10.1046/j.1365-2958.1999.01558.x. View