Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro

Recuenco, Frances C.; Kobayashi, Kanae; Ishiwa, Akiko; Enomoto-Rogers, Yukiko; Fundador, Noreen Grace V.; Sugi, Tatsuki; Takemae, Hitoshi; Iwanaga, Tatsuya; Murakoshi, Fumi; Gong, Haiyan; Inomata, Atsuko; Horimoto, Taisuke; Iwata, Tadahisa; Kato, Kentaro

doi:10.1038/srep04723

Cited by 27 publications

(18 citation statements)

References 53 publications

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“…However, other sulphated polysaccharides, including heparin, fucoidan, and dextran sulfate [ 28 , 29 ] have shown promising in vitro anti-malarial activity. An example is the previous report on gellan sulfate [ 30 ] that demonstrated that chemical modification, namely, sulphation, could change the characteristics of these compounds. Given that these polysaccharides are still considered promising potential anti-malaria drugs, chemical modification might decrease the side effects of such compounds.…”

Section: Discussionmentioning

confidence: 99%

Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice

Recuenco

Takano

Chiba

et al. 2014

Malar J

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BackgroundThere is an urgent need to develop and test novel compounds against malaria infection. Carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit Plasmodium falciparum in vitro. However, they are inflammatory and alter the permeability of the blood–brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (CM), a severe complication of the disease. In this work, the authors look into the effects of the administration of λ-carrageenan to the development and severity of CM in BALB/c mice, a relatively non-susceptible model, during infection with the ANKA strain of Plasmodium berghei.MethodsFive-week-old female BALB/c mice were infected with P. berghei intraperitoneally. One group was treated with λ-carrageenan (PbCGN) following the 4-day suppressive test protocol, whereas the other group was not treated (PbN). Another group of healthy BALB/c mice was similarly given λ-carrageenan (CGN) for comparison. The following parameters were assessed: parasitaemia, clinical signs of CM, and mortality. Brain and other vital organs were collected and examined for gross and histopathological lesions. Evans blue dye assays were employed to assess blood–brain barrier integrity.ResultsPlasmodium berghei ANKA-infected BALB/c mice treated with λ-carrageenan died earlier than those that received no treatment. Histopathological examination revealed that intracerebral haemorrhages related to CM were present in both groups of infected BALB/c mice, but were more numerous in those treated with λ-carrageenan than in mock-treated animals. Inflammatory lesions were also observed only in the λ-carrageenan-treated mice. These observations are consistent with the clinical signs associated with CM, such as head tilt, convulsions, and coma, which were observed only in this group, and may account for the earlier death of the mice.ConclusionThe results of this study indicate that the administration of λ-carrageenan exacerbates the severe brain lesions and clinical signs associated with CM in BALB/c mice infected with P. berghei ANKA.

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Section: Discussionmentioning

confidence: 99%

Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice

Recuenco

Takano

Chiba

et al. 2014

Malar J

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“…Recently, sulfated polysaccharides have been analyzed as drug candidates for protozoan infectious diseases [ 3 , 85 , 86 ]. According to our data, the sulfated positions in the carbohydrates can be critical for the inhibitory quality [ 3 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

The Role of Carbohydrates in Infection Strategies of Enteric Pathogens

Kato

Ishiwa

2015

Trop.Med.Health

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Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.

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“…In vitro invasion assay. The invasion assay was conducted according a previous method (24). P. falciparum was cultured in RPMI-1640 medium supplemented with 10% human serum and erythrocytes (2% hematocrit) at 37˚C and then flushed with a gas mixture containing 5% O 2 , 5% CO 2 and 90% N 2 .…”

Section: Expression and Purification Of The Pftip-gst Proteinmentioning

confidence: 99%

Characterization of the malaria parasite protein PfTip, a novel invasion-related protein

Liu

Huang

et al. 2016

Molecular Medicine Reports

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Malaria is one of the most common infective diseases in the world. Invasion of host erythrocytes by the malaria parasite is crucial for pathogen survival and pathogenesis. Various proteins mediate parasite invasion and identification of novel invasion-related proteins may aid in elucidating the underlying molecular mechanism and new intervention strategies for malaria control. This study characterized the PfTip protein, a homolog of the human T‑cell immunomodulatory protein, and examined its function in preventing parasite infection. Bioinformatics analysis and experimental validation were adopted in the present study. Bioinformatics analysis showed that PfTip has a β‑propeller fold in its structure and is highly expressed at the early ring stage. TNFRSF14 was predicted to be a candidate interactant of PfTip. Further analyses showed that PfTip blockage by sera inhibited erythrocyte invasion by the malaria parasite. The protective effect of PfTip was further confirmed through in vivo analysis. To the best of our knowledge, this study is the first to provide evidence on the function of PfTip in erythrocyte parasite invasion. Additional assays involving the receptor of this protein are currently underway.

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Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro

Cited by 27 publications

References 53 publications

Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice

Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice

The Role of Carbohydrates in Infection Strategies of Enteric Pathogens

Characterization of the malaria parasite protein PfTip, a novel invasion-related protein

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