Cooperativity in the binding of the cationic biocide polyhexamethylene biguanide to nucleic acids

Allen, Michael J.; Morby, Andrew P.; White, Graham F.

doi:10.1016/j.bbrc.2004.04.043

Cited by 56 publications

(46 citation statements)

References 25 publications

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“…Recently we demonstrated a strong cooperative binding between PHMB and DNA, leading to co-precipitation in vitro (Allen et al, 2004). This discovery, taken together with the present results, indicates that the critical factor underlying the different effects at bacteriostatic and bactericidal levels of PHMB may not be the ability to disrupt the inner membrane (as previously thought), but the direct interaction between PHMB and genomic DNA.…”

Section: A New Theory For the Phmb Mechanism Of Actionsupporting

confidence: 57%

“…Recently, we showed that PHMB interacts strongly and cooperatively with nucleic acids in vitro and that the structural status of the nucleic acid affects the nature of its initial interactions with PHMB (Allen et al, 2004). Here we show that the interaction of PHMB with nucleic acids in vitro has a parallel in vivo, giving a novel facet to the action of PHMB.…”

Section: Nhcn] As End-groupsmentioning

confidence: 79%

“…Moreover, the smallest functional units are dimers which may oligomerize and effectively cross-link adjacent DNA segments of DNA through an oligomeric matrix of H-NS (Dorman, 2004). This process could have a direct protective role against PHMB, because the latter is also known to interact strongly and cooperatively with DNA to create cross-links (Allen et al, 2004) and thus potentially to interfere with DNAmetabolism (replication, repair, transcription, etc.). Competitive binding by H-NS would mitigate against such adverse effects of PHMB.…”

Section: Dna-binding Proteinsmentioning

confidence: 99%

“…Overexpression of recA in the wild-type strain led to a stronger resistance to PHMB. If PHMB is indeed gaining access to the cytoplasm and interacting with genomic DNA (Allen et al, 2004), the induction of RecA could either help to repair the damage effected by PHMB, or be part of a damage signal that leads to other events affecting the phenotype, or contribute to an increased capacity to generate diversity (cf. ycgW below).…”

Section: Dna-binding Proteinsmentioning

confidence: 99%

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The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide

2006

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The global response of Escherichia coli to the broad-spectrum biocide polyhexamethylene biguanide (PHMB) was investigated using transcriptional profiling. The transcriptional analyses were validated by direct determination of the PHMB-tolerance phenotypes of derivatives of E. coli MG1655 carrying either insertionally inactivated genes and/or plasmids expressing the cognate open reading frames from a heterologous promoter in the corresponding chromosomally inactivated strains. The results showed that a wide range of genes was altered in transcriptional activity and that all of the corresponding knockout strains subsequently challenged with biocide were altered in tolerance. Of particular interest was the induction of the rhs genes and the implication of enzymes involved in the repair/binding of nucleic acids in the generation of tolerance, suggesting a novel dimension in the mechanism of action of PHMB based on its interaction with nucleic acids.

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Section: A New Theory For the Phmb Mechanism Of Actionsupporting

confidence: 57%

Section: Nhcn] As End-groupsmentioning

confidence: 79%

Section: Dna-binding Proteinsmentioning

confidence: 99%

Section: Dna-binding Proteinsmentioning

confidence: 99%

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The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide

2006

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“…Guanidine-based antimicrobials were thus believed to have low toxicity to humans (Ikeda et al, 1983(Ikeda et al, , 1984. However, recent accounts have reported PHMB penetrating mammalian cells and interacting with chromosomes, raising concerns about health hazards from guanidine-based antimicrobials (Allen et al, 2004(Allen et al, , 2006Chindera et al, 2016;Firdessa et al, 2015).…”

Section: Biocidal Properties Of Phmg-pmentioning

confidence: 99%

Adverse health effects of humidifier disinfectants in Korea: lung toxicity of polyhexamethylene guanidine phosphate

et al. 2016

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-Exposure to humidifier disinfectants was identified in 2011 as the potential cause of an outbreak of lung disease in Korea. It is estimated that over 8 million people have been exposed to humidifier disinfectants-chemicals added to the water used in humidifiers to prevent the growth of microorganisms-since their commercial introduction. The primary component of humidifier disinfectant products involved was polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent. Lesions observed in the lungs of patients were similar to those observed in laboratory animals exposed to PHMG-P. In this review, we outline the physicochemical and toxicological properties of PHMG-P, and introduce a putative mechanism for its lung toxicity based in large part on research findings to date.

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Types of Microbicidal and Microbistatic Agents

Al-Adham

Haddadin

Collier

2012

Russell, Hugo &Amp; Ayliffe's

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Cooperativity in the binding of the cationic biocide polyhexamethylene biguanide to nucleic acids

Cited by 56 publications

References 25 publications

The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide

The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide

Adverse health effects of humidifier disinfectants in Korea: lung toxicity of polyhexamethylene guanidine phosphate

Types of Microbicidal and Microbistatic Agents

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