Functions of potA and potD proteins in spermidine-preferential uptake system in Escherichia coli.

Kashiwagi, Keiko; Miyamoto, Saku; Nukui, Eiji; Kobayashi, Hiroshi; Igarashi, Kazuei

doi:10.1016/s0021-9258(19)36522-6

Cited by 76 publications

(13 citation statements)

References 46 publications

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“…Previous efforts have shown that specific cell types can be targeted via the molecular recognition events involved during the import of exogenous polyamines. − Prior work in our laboratories evaluated the cytotoxicity and polyamine transporter (PAT) affinity of conjugates containing branched 1,2 and linear polyamine motifs 3,4 attached to either an anthracene or acridine nucleus. ,, Indeed, certain linear triamines motifs were identified as excellent vector systems. , In particular, the 4,4-triamine conjugate 4 (Figure , 4 ) had 150-fold higher cytotoxicity in CHO cells (which contained an active polyamine transport system) than in a mutant CHO- MG cell line, which was PAT-deficient. ,,, Therefore, cells which contain an active polyamine transport system were much more sensitive to certain polyamine−anthracene conjugates. The observed differential cytotoxicity formed the basis of a selective chemotherapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Defining the Molecular Requirements for the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters

et al. 2003

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Several N(1)-substituted polyamines containing various spacer units between nitrogen centers were synthesized as their respective HCl salts. The N(1)-substituents included benzyl, naphthalen-1-ylmethyl, anthracen-9-ylmethyl, and pyren-1-ylmethyl. The polyamine spacer units ranged from generic (4,4-triamine, 4,3-triamine, and diaminooctane) spacers to more exotic [2-(ethoxy)ethanoxy-containing diamine, hydroxylated 4,3-triamine, and cyclohexylene-containing triamine] spacers. Two control compounds were also evaluated: N-(anthracen-9-ylmethyl)-butylamine and N-(anthracen-9-ylmethyl)-butanediamine. Biological activities in L1210 (murine leukemia), alpha-difluoromethylornithine (DFMO)-treated L1210, and Chinese hamster ovary (CHO) and its polyamine transport-deficient mutant (CHO-MG) cell lines were investigated via IC(50) cytotoxicity determinations. K(i) values for spermidine uptake were also determined in L1210 cells. Of the series studied, the N(1)-benzyl-4,4-triamine system 6 had significantly higher IC(50) values (lower cytotoxicity) in the L1210, CHO, and CHO-MG cell lines. A cellular debenzylation process was observed in L1210 cells with 6 and generated "free" homospermidine. The size of the N(1)-arylmethyl substituent had direct bearing on the observed cytotoxicity in CHO-MG cells. The N(1)-naphthalenylmethyl, N(1)-anthracenylmethyl, and N(1)-pyrenylmethyl 4,4-triamines had similar toxicity (IC(50)s: approximately 0.5 microM) in CHO cells, which have an active polyamine transporter (PAT). However, this series had IC(50) values of >100 microM, 66.7 microM, and 15.5 microM, respectively, in CHO-MG cells, which are PAT-deficient. The observed lower cytotoxicity in the PAT-deficient CHO-MG cell line supported the premise that the conjugates use PAT for cellular entry. In general, moderate affinities for the polyamine transporter were observed for the N-arylmethyl 4,4-triamine series with their L1210 K(i) values all near 3 microM. In summary, the 4,4-triamine motif was shown to facilitate entry of polyamine conjugates into cells containing active polyamine transporters.

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Section: Introductionmentioning

confidence: 99%

Defining the Molecular Requirements for the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters

et al. 2003

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“…5 B ). From a metabolic standpoint, PGT8 also contains a gene cluster indicated as potA , a spermidine/putrescine transport system that has been studied in E. coli ( 77 ). Interestingly, spermidine biosynthesis pathway genes and transporter components, including potA , have been shown to be up-regulated during temperature and alkali stress in C. difficile ( 78 ).…”

Section: Resultsmentioning

confidence: 99%

Systems biology approach to functionally assess the Clostridioides difficile pangenome reveals genetic diversity with discriminatory power

Norsigian

Danhof

Brand

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Clostridioides difficile infections are the most common source of hospital-acquired infections and are responsible for an extensive burden on the health care system. Strains of the C. difficile species comprise diverse lineages and demonstrate genome variability, with advantageous trait acquisition driving the emergence of endemic lineages. Here, we present a systems biology analysis of C. difficile that evaluates strain-specific genotypes and phenotypes to investigate the overall diversity of the species. We develop a strain typing method based on similarity of accessory genomes to identify and contextualize genetic loci capable of discriminating between strain groups.

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“…Also, polyamines such as putrescine and spermidine have been suggested to exhibit chaperone activities when cells are exposed to stressful environments such as antibiotic therapies [21]. Taken together, the role polyamines and heat shock proteins play in a cellular system suggests that Plasmodium falciparum could apply similar methods to render current drugs ineffective by keeping the system's proteins in good shape (properly folded) during drug treatment [22]. In general, obligate human parasites depend upon a robust protein quality control system to ensure their survival, and hence, both employ a competent heat shock machinery and polyamines to this end.…”

Section: The Life Cycle Of Plasmodium Falciparum Parasitementioning

confidence: 99%

“…Co-chaperone Geldanamycin, radicicol, celastrol [15,23] Hsp 70 Foldase, holdase, transportation Geldanamycin [24] Hsp 90 Foldade and holdase Geldanamycin, benzoquinone [25,26] Hsp 110 Foldase Geldanamycin [16,27] Small Hsps Modulation and stabilization [19,20,22,26] Table 1.…”

Section: The Functional Activities Of Hsp70 In Partnership With Hsp40mentioning

confidence: 99%

A Double Line of Defense: Heat Shock Proteins and Polyamines Act as Contributing Factors to Drug Resistance of some Plasmodium Parasites

Makhoba¹

2021

Plasmodium Species and Drug Resistance

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Malaria remains a threat to human life worldwide with children under the age of 5 being the most vulnerable. Plasmodium falciparum, known as the causative agent of the deadliest malaria, survives both in the mosquito vector and human host. The sudden temperature change seems to not affect the parasite’s cellular system. Heat shock proteins and polyamines are the major house-keepers of the parasite’s cellular system to remain viable, despite the temperature changes that the parasite gets exposed to. While heat shock proteins protect newly synthesized proteins until they are properly folded polyamines are needed for cell differentiation, proliferation, and cell growth. In plants for example, polyamines have been reported to act as molecular chaperones when cells are exposed to unfavorable conditions that could be detrimental to cells. In this review, the role of heat shock proteins and polyamines in plasmodium parasite drug resistance and their role in parasite survival are discussed. The current drugs against malaria as well as the alternative future approach towards malarial drug development are reviewed.

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Functions of potA and potD proteins in spermidine-preferential uptake system in Escherichia coli.

Cited by 76 publications

References 46 publications

Defining the Molecular Requirements for the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters

Defining the Molecular Requirements for the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters

Systems biology approach to functionally assess the Clostridioides difficile pangenome reveals genetic diversity with discriminatory power

A Double Line of Defense: Heat Shock Proteins and Polyamines Act as Contributing Factors to Drug Resistance of some Plasmodium Parasites

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