A Search for Pseudomonas Alginate Biosynthesis Inhibitors from Microbial Metabolites

Nakagawa, Akira; Hosoyama, Takayuki; Chubachi, Kazuyoshi; Takahashi, Senji; Ohkubo, Toyoji; Iyobe, Shizuko

doi:10.7164/antibiotics.50.286

Cited by 4 publications

(3 citation statements)

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“…Penicillic acid is an antibiotic mycotoxin. It has been identified interrupting the biofilm formation by the inhibition of alginate biosynthesis in P. aeruginosa at the low concentrations . Moreover, penicillic acid is screened out as a quorum sensing inhibitor from the extracts of the Penicillium species.…”

Section: Discussionmentioning

confidence: 99%

Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Qin

Sun

Yang

et al. 2016

J. Basic Microbiol.

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Bacterial growth phase has been reported affecting phage infection. To underpin the related mechanism, infection efficiency of Pseudomonas aeruginosa phage K5 is characterized. When infecting the logarithmic cells, phage K5 produced significantly more infection centers than the stationary cells, well concordant with the viable cell ratio in the different growth phases. Additionally, the burst size decreased dramatically in the stationary cells, implying that the physiological state of the viable cells contributed to the productivity of phage K5, and it was consistent with the expression variation of the phage RNA polymerase. Quorum sensing inhibitor penicillic acid was applied and could significantly improve the viable cell proportion and the infection center numbers, but had less effect on the corresponding burst sizes. Moreover, the effect of penicillic acid and the quorum sensing regulator mutants on the production of phage C11 was also analyzed. Taken together, our data suggest that quorum sensing is involved in the defense of phage K5 infection by influencing the viable cell population and their physiological state, and it is an efficient and intrinsic pathway allowing bacteria to resist phage attacks in natural environment.

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Section: Discussionmentioning

confidence: 99%

Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Qin

Sun

Yang

et al. 2016

J. Basic Microbiol.

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“…The high-resolution structural information on the active site has revealed residues critical for substrate specificity and will aid in the process of inhibitor design. Several commercially available compounds are known inhibitors of GMD, including penicillic acid and macrolide antibiotics such as erythromycin (41), and are excellent initial candidates for complex formation and structural characterization. The GMD structure also serves as a model for other members of this enzyme family, including GMD from the plant pathogen P. syringae.…”

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confidence: 99%

Crystal Structure of GDP-Mannose Dehydrogenase: A Key Enzyme of Alginate Biosynthesis in P. aeruginosa^,

2003

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The enzyme GMD from Pseudomonas aeruginosa catalyzes the committed step in the synthesis of the exopolysaccharide alginate. Alginate is a major component of P. aeruginosa biofilms that protect the bacteria from the host immune response and antibiotic therapy. The 1.55 A crystal structure of GMD in ternary complex with its cofactor NAD(H) and product GDP-mannuronic acid reveals that the enzyme forms a domain-swapped dimer with two polypeptide chains contributing to each active site. The extensive dimer interface provides multiple opportunities for intersubunit communication. Comparison of the GMD structure with that of UDP-glucose dehydrogenase reveals the structural basis of sugar binding specificity that distinguishes these two related enzyme families. The high-resolution structure of GMD provides detailed information on the active site of the enzyme and a template for structure-based inhibitor design.

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“…Alginate is involved in many processes during P. aeruginosa infection, providing protection against a variety of host defense mechanisms and environmental factors such as antimicrobial agents; it also is highly present in mucoid bio-films and facilitates medical device colonization. 105 , 107 , 126 This exopolysaccharide, principally exhibited by mucoid strains of P. aeruginosa , is capable of reducing the host immune response by interfering with the activation of complements and polymorphonuclear chemotaxis, and also was shown to play a role in decreasing the phagocytosis of Pseudomonas spp., both those that are planktonic and those that form bio-film structure guaranteeing the P. aeruginosa survival during the first steps of primary infection, its permanency, and its chronic colonization development. 105 , 107 , 127…”

Section: Pathogenicity and Newer Adjunctive Therapiesmentioning

confidence: 99%

Pseudomonas aeruginosa ventilator-associated pneumonia management

Ramirez-Estrada¹,

Borgatta²,

Rello³

2016

IDR

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Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising.

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A Search for Pseudomonas Alginate Biosynthesis Inhibitors from Microbial Metabolites

Cited by 4 publications

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Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Crystal Structure of GDP-Mannose Dehydrogenase: A Key Enzyme of Alginate Biosynthesis in P. aeruginosa^,

Pseudomonas aeruginosa ventilator-associated pneumonia management

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A Search for Pseudomonas Alginate Biosynthesis Inhibitors from Microbial Metabolites

Cited by 4 publications

References 0 publications

Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Quorum sensing influences phage infection efficiency via affecting cell population and physiological state

Crystal Structure of GDP-Mannose Dehydrogenase: A Key Enzyme of Alginate Biosynthesis in P. aeruginosa,

Pseudomonas aeruginosa ventilator-associated pneumonia management

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Crystal Structure of GDP-Mannose Dehydrogenase: A Key Enzyme of Alginate Biosynthesis in P. aeruginosa^,