Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design

Akula, Nagaraju; Hong, Zheng; Han, Frank Q.; Wang, Nian

doi:10.1016/j.bmcl.2011.05.086

Cited by 38 publications

(34 citation statements)

References 18 publications

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“…Our data also showed that Las lepB gene can partially complement the E.coli lepB amber mutant. Due to the importance of Sec-translocon and its substrate, suppression of the Sec secretion system by developing antimicrobials targeting suitable targets, e.g., SecA, has the potential to inhibit HLB progression (Akula et al, 2011). …”

Section: Resultsmentioning

confidence: 99%

SEC-Translocon Dependent Extracytoplasmic Proteins of Candidatus Liberibacter asiaticus

Prasad

Zhang

et al. 2016

Front. Microbiol.

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Citrus Huanglongbing (HLB) is the most destructive citrus disease worldwide. HLB is associated with three species of the phloem-limited, gram-negative, fastidious α-proteobacteria: Candidatus Liberibacter asiaticus (Las), Ca. L. americanus (Lam), and Ca. L. africanus (Laf) with Las being the most widespread species. Las has not been cultured in artificial media, which has greatly hampered our efforts to understand its virulence mechanisms. Las contains a complete Sec-translocon, which has been suggested to transport Las proteins including virulence factors into the extracytoplasmic milieu. In this study, we characterized the Sec-translocon dependent, signal peptide containing extracytoplasmic proteins of Las. A total of 166 proteins of Las-psy62 strain were predicted to contain signal peptides targeting them out of the cell cytoplasm via the Sec-translocon using LipoP, SigalP 3.0, SignalP 4.1, and Phobius. We also predicated SP containing extracytoplasmic proteins for Las-gxpsy and Las-Ishi-1, Lam, Laf, Ca. L. solanacearum (Lso), and L. crescens (Lcr). For experimental validation of the predicted extracytoplasmic proteins, Escherichia coli based alkaline phosphatase (PhoA) gene fusion assays were conducted. A total of 86 out of the 166 predicted Las proteins were experimentally validated to contain signal peptides. Additionally, Las-psy62 lepB (CLIBASIA_04190), the gene encodes signal peptidase I, was able to partially complement the amber mutant of lepB of E. coli. This work will contribute to the identification of Sec-translocon dependent effector proteins of Las, which might be involved in virulence of Las.

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Section: Resultsmentioning

confidence: 99%

SEC-Translocon Dependent Extracytoplasmic Proteins of Candidatus Liberibacter asiaticus

Prasad

Zhang

et al. 2016

Front. Microbiol.

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“…29 Subsequent to our effort, a series of thiazolo [4, 5-d] pyrimidine derivatives was reported by Jeng and co-workers as SecA inhibitors with the best compounds having IC 50 value of 135 µM against EcSecA intrinsic ATPase and 200 µM against translocation SecA ATPase activities. 30 In a recent study, SecA inhibitors were reported for a citrus plant bacterium Candidatus Liberibacter asiaticus (Las) 31 and the most potent inhibitor obtained showed an IC 50 of 0.25 µM. We have also reported a fluorescein 32 analog, Rose Bengal (RB), as a sub-micromolar inhibitor of bacterial protein translocation through inhibition of SecA activity.…”

Section: Introductionmentioning

confidence: 90%

Design, syntheses and evaluation of 4-oxo-5-cyano thiouracils as SecA inhibitors

Chaudhary

Jin

Chen

et al. 2015

Bioorganic & Medicinal Chemistry

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“…In a recent study, SecA inhibitors were reported for a citrus plant bacterium Candidatus Liberibacter asiaticus (Las) responsible for causing Huanglongbing citrus disease [147]. A homology model of Las SecA was derived from E. coli SecA and used for virtual screening studies.…”

Section: Reported Seca Inhibitorsmentioning

confidence: 99%

SecA: A Potential Antimicrobial Target

et al. 2015

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There is a consensus in the medical profession of the pressing need for novel antimicrobial agents due to issues related to drug resistance. In practice, solutions to this problem to a large degree lie with the identification of new and vital targets in bacteria and subsequently designing their inhibitors. We consider SecA a very promising antimicrobial target. In this review, we compile and analyze information available on SecA to show that inhibition of SecA has a multitude of consequences. Furthermore, we discuss issues critical to the design and evaluation of SecA inhibitors.

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Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design

Cited by 38 publications

References 18 publications

SEC-Translocon Dependent Extracytoplasmic Proteins of Candidatus Liberibacter asiaticus

SEC-Translocon Dependent Extracytoplasmic Proteins of Candidatus Liberibacter asiaticus

Design, syntheses and evaluation of 4-oxo-5-cyano thiouracils as SecA inhibitors

SecA: A Potential Antimicrobial Target

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