Applications of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) for health care based on macrophage network theory

Kohchi, Chie; Inagawa, Hiroyuki; Nishizawa, Takashi; Yamaguchi, Takatoshi; Nagai, Shiro; Soma, Gen‐Ichiro

doi:10.1263/jbb.102.485

Cited by 59 publications

(71 citation statements)

References 45 publications

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“…The question raised by many authors whether exposure to dust-borne endotoxin protects against cancer was not unequivocally solved to-date, but certainly deserves attention in the light of successful treatment of cancer with the use of P. agglomerans LPS achieved by Japanese scientists [13,105,106], which will be discussed in detail in the last article of this Pantoea-series. Henderson and Enterline [107] and Enterline et al [108] expressed an opinion that exposure to airborne endotoxin decreases cancer mortality in cotton workers.…”

Section: Dust-borne Endotoxins and Allergens Of Pantoea Agglomerans -mentioning

confidence: 99%

“…The bacterium also occurs abundantly in plant and animal products, in the body of arthropods and other animals, in water, soil, dust and air, and occasionally in humans [7,9,10]. From the human viewpoint, the role of this organism is ambiguous -both deleterious and beneficial: on one side, it causes disorders in people exposed to inhalation of organic dusts [11] and diseases of crops [12], and on the other, it produces substances effective in the treatment of cancer and other diseases of humans and animals [13], suppresses the development of various plant pathogens by antibiotic production and/or competition [7,14], promotes plant growth by nitrogen fixation and other mechanisms [5,7,8], and appears as a potentially efficient bio-fertilizer and bio-remediator [7,15]. Unraveling these problems is a fascinating experience for any scientist.…”

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confidence: 99%

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<i>Pantoea agglomerans</i>: a marvelous bacterium of evil and good. Part I. Deleterious effects: Dust-borne endotoxins and allergens – focus on cotton dust

Dutkiewicz¹,

Maćkiewicz²,

Lemieszek³

et al. 2015

Ann Agric Environ Med.

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The ubiquitous Gram-negative bacterium Pantoea agglomerans (synonyms: Enterobacter agglomerans, Erwinia herbicola) is known both as an epiphytic microbe developing on the surface of plants, and as an endophytic organism living inside the plants. The bacterium also occurs abundantly in plant and animal products, in the body of arthropods and other animals, in water, soil, dust and air, and occasionally in humans. From the human viewpoint, the role of this organism is ambiguous -both deleterious and beneficial: on one side it causes disorders in people exposed to inhalation of organic dusts and diseases of crops, and on the other it produces substances effective in the treatment of cancer and other diseases of humans and animals, suppresses the development of various plant pathogens, promotes plant growth, and appears as a potentially efficient biofertilizer and bioremediator. P. agglomerans has been identified as a predominant bacterium on cotton plants grown worldwide, usually as an epiphyte, rarely as pathogen. It is particularly numerous on cotton bract after senescence. During the processing of cotton in mills, bacteria and their products are released with cotton dust into the air and are inhaled by workers, causing respiratory and general disorders, usually defined as byssinosis. The most adverse substance is endotoxin, a heteropolymer macromolecule present in the outermost part of the cell wall, consisting of lipopolysaccharide (LPS) as a major constituent, phospholipids and protein. Numerous experiments carried out in last quarter of 20th century on laboratory animals and human volunteers supported convincing evidence that the inhaled endotoxin produced by P. agglomerans causes numerous pathologic effects similar to those elicited by cotton dust, such as the influx of free lung cells into airways and activation of alveolar macrophages which secrete mediators (prostaglandins, platelet-activating factor, interleukin-1, tumour necrosis factor) that cause the accumulation of platelets in pulmonary capillaries, initiating acute and chronic inflammation, resulting in endothelial cell damage and extravasation of cells and fluids into the lung interstitium. These changes cause bronchoconstriction, the decrement of lung function expressed as reduction of forced expiratory volume in one second (FEV 1 ) and/or diffusion capacity, increase in the airway hyper-reactivity and subjective symptoms such as fever, airway irritation and chest tightness. The conclusions from these experiments, performed mostly 20-30 years ago, did not loose their actuality until recently. This was because to-date no other cotton dust component had been identified as a more important work-related hazard than bacterial endotoxin. Although other microbial and plant constituents are also considered as potential causative agents of byssinosis, the endotoxin produced by Pantoea agglomerans and other Gram-negative bacteria present in cotton dust, is still regarded as a major cause of this mysterious disease. Key wordsPantoea agglomerans, end...

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Section: Dust-borne Endotoxins and Allergens Of Pantoea Agglomerans -mentioning

confidence: 99%

mentioning

confidence: 99%

<i>Pantoea agglomerans</i>: a marvelous bacterium of evil and good. Part I. Deleterious effects: Dust-borne endotoxins and allergens – focus on cotton dust

Dutkiewicz¹,

Maćkiewicz²,

Lemieszek³

et al. 2015

Ann Agric Environ Med.

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“…However, in contrast to systemic injection, no toxicity of LPS has been reported when it has been orally administrated in safety tests: the oral administration of 1,000 mg/kg IP-PA1 for 28 days generated no toxic effects in rats [18,35]. In addition, IP-PA1 derived from symbiotic gram-negative bacteria found in crops is considered safe because it has been ingested by humans and animals for a long time [20]. Therefore, IP-PA1 is expected to act as an immunomodulator, which is one of major reasons why we assessed immunological effects and the usefulness of orally-administered IP-PA1 in melanoma therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) is a low-molecular-weight (5 kDa) lipopolysaccharide (LPS) derived from the cell walls of a symbiotic gram-negative bacteria commonly found in various food crops, such as cereals, fruits, and vegetables [17,18,20,27]. IP-PA1 has immune-enhancing functions such as protection from bacterial and parasitic infections in mice [8,20,32], and recovery from stress-induced immunosuppression in chickens [14].…”

Section: Introductionmentioning

confidence: 99%

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Oral Administration of Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Improves the Survival of B16 Melanoma-Inoculated Model Mice

et al. 2011

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Abstract:To investigate the usefulness of the immunopotentiator from Pantoea agglomerans 1 (IP-PA1) as a supportive drug in melanoma therapy, we analyzed the immunological effects of IP-PA1 on melanoma-inoculated model mice. Oral administration of IP-PA1 increased the serum levels of tumor necrosis factor (TNF)-α at 2 h after the administration and interferon (IFN)-γ and IL-12 at 12 h after the administration in naïve BALB/cCrSlc mice as evaluated by ELISA. IP-PA1 did not affect the proliferation of melanoma cells directly determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Combinatory treatment of IP-PA1 with doxorubicin for 9 days increased the serum levels of IFN-γ and IL-12 by 71.0 and 15.3%, respectively, compared to the treatment of doxorubicin alone in melanoma-bearing C57BL/6NCrSlc mice as evaluated by ELISA. It also increased the proportion of natural killer (NK) cells and the ratio of CD4 + to CD8 + T cells in the spleen from 6.1 ± 0.3 to 7.4 ± 0.5% and from 1.25 ± 0.03 to 1.38 ± 0.04, respectively, compared to the treatment of doxorubicin alone as analyzed by flow cytometry. The mean survival period of melanoma-bearing, doxorubicin treated mice was prolonged from 31.4 ± 7.1 to 35.3 ± 8.4, 51.1 ± 5.4, and 45.0 ± 8.4 days by combinatory treatment of IP-PA1 at the daily doses of 0.1, 0.5, and 1 mg/kg, respectively. In conclusion, the results of the present study suggest the usefulness of IP-PA1 as a supportive drug in melanoma therapy.

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Chemical Synthesis of Acetobacter pasteurianus Lipid A with a Unique Tetrasaccharide Backbone and Evaluation of Its Immunological Functions

Yamaura,

Shimoyama,

Hosomi

et al. 2024

Angewandte Chemie

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Lipopolysaccharide (LPS), a cell surface component of Gram‐negative bacteria, activates innate immunity. Its active principle is the terminal glycolipid lipid A. Acetobacter pasteurianus is a Gram‐negative bacterium used in the fermentation of traditional Japanese black rice vinegar (kurozu). In this study, we focused on A. pasteurianus lipid A, which is a potential immunostimulatory component of kurozu. The active principle structure of A. pasteurianus lipid A has not yet been identified. Herein, we first systematically synthesized three types of A. pasteurianus lipid As containing a common and unique tetrasaccharide backbone. We developed an efficient method for constructing the 2‐trehalosamine skeleton utilizing borinic acid‐catalyzed glycosylation to afford 1,1’‐α,α‐glycoside in high yield and stereoselectivity. A common tetrasaccharide intermediate with an orthogonal protecting group pattern was constructed via [2+2] glycosylation. After introducing various fatty acids, all protecting groups were removed to achieve the first chemical synthesis of three distinct types of A. pasteurianus lipid As. After evaluating their immunological function using both human and murine cell lines, we identified the active principles of A. pasteurianus LPS. We also found the unique anomeric structure of A. pasteurianus lipid A contributes to its high chemical stability.

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Applications of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) for health care based on macrophage network theory

Cited by 59 publications

References 45 publications

<i>Pantoea agglomerans</i>: a marvelous bacterium of evil and good. Part I. Deleterious effects: Dust-borne endotoxins and allergens – focus on cotton dust

<i>Pantoea agglomerans</i>: a marvelous bacterium of evil and good. Part I. Deleterious effects: Dust-borne endotoxins and allergens – focus on cotton dust

Oral Administration of Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Improves the Survival of B16 Melanoma-Inoculated Model Mice

Chemical Synthesis of Acetobacter pasteurianus Lipid A with a Unique Tetrasaccharide Backbone and Evaluation of Its Immunological Functions

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