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In-vitro archaeacidal activity of biocides against human-associated archaea.

Khelaifia S, Brunel JM, Michel JB, Drancourt M - PLoS ONE (2013)

Bottom Line: However, no biocide activity has been reported among these human-associated archaea.Squalamine derivative S1 exhibited a 10-200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea.As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Université, URMITE, UMR63 CNRS 7278, IRD 198, Inserm 1095, Marseille, France.

ABSTRACT

Background: Several methanogenic archaea have been detected in the human intestinal microbiota. These intestinal archaea may contaminate medical devices such as colonoscopes. However, no biocide activity has been reported among these human-associated archaea.

Methodology: The minimal archaeacidal concentration (MAC) of peracetic acid, chlorhexidine, squalamine and twelve parent synthetic derivatives reported in this study was determined against five human-associated methanogenic archaea including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanobrevibacter arboriphilicus, Methanosphaera stadtmanae, Methanomassiliicoccus luminyensis and two environmental methanogens Methanobacterium beijingense and Methanosaeta concilii by using a serial dilution technique in Hungates tubes.

Principal findings: MAC of squalamine derivative S1 was 0.05 mg/L against M. smithii strains, M. oralis, M. arboriphilicus, M. concilii and M. beijingense whereas MAC of squalamine and derivatives S2-S12 varied from 0.5 to 5 mg/L. For M. stadtmanae and M. luminyensis, MAC of derivative S1 was 0.1 mg/L and varied from 1 to ≥ 10 mg/L for squalamine and its parent derivatives S2-S12. Under the same experimental conditions, chlorhexidine and peracetic acid lead to a MAC of 0.2 and 1.5 mg/L, respectively against all tested archaea.

Conclusions/significance: Squalamine derivative S1 exhibited a 10-200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea. As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea.

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Related in: MedlinePlus

Images by electron microscopy demonstrating the morphological effects of squalamine on M. smithii cell wall.(A) M. smithii without squalamine. (B) M. smithii +1 mg/L squalamine. White arrows show holes caused by squalamine on M. smithii cell wall. The scale bar corresponds to 500 nm.
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pone-0062738-g003: Images by electron microscopy demonstrating the morphological effects of squalamine on M. smithii cell wall.(A) M. smithii without squalamine. (B) M. smithii +1 mg/L squalamine. White arrows show holes caused by squalamine on M. smithii cell wall. The scale bar corresponds to 500 nm.

Mentions: Two commonly used biocides chlorhexidine and peracetic acid, exhibited an archaeacidal activity under current decontamination protocols and by using concentrations of 0.2 and 1.5 g/L, respectively. However, squalamine and its derivatives exhibited a higher activity than these two usual biocides on the majority of here tested archaea, not on all archaea. Interestingly, these compounds are equally active against Gram-negative and Gram-positive bacteria, including bacteria from the human intestinal microbiota [17], [20]. They act directly on the cell membrane of the bacteria by creating holes (Figure 3), emptying the cell cytoplasms which lead to the death of the bacteria [17]. Data herein reported indicate that some squalamine derivatives exhibited an increased in-vitro activity against methanogenic archaea, particularly for derivative S1. Indeed, the structure of the different squalamine derivatives greatly influences their archaeacidal activity: aminosterol derivatives from dehydroepiandrosterone (DHEA) demonstrate a lower activity (around 5 µg/mL) compared to pregnenolone derivatives (0.05 to 0.5 µg/mL) while they differ only by the length of the side chain in position 17 suggesting a required specific conformation by targeting archaea. On the other hand, even in the same series the activity is conserved whatever the nature of the amino side chain introduced except for derivative S1 which is ten times more active and which differs only by the presence of three positive charges instead of two in all the other products suggesting a potent interaction of the positive charge of the compound with the negative charge of the archaeal membrane (Figure 1). All these features constitute a basis for the development of a new class of biocides devoted to the decontamination of archaea-contaminated medical devices.


In-vitro archaeacidal activity of biocides against human-associated archaea.

Khelaifia S, Brunel JM, Michel JB, Drancourt M - PLoS ONE (2013)

Images by electron microscopy demonstrating the morphological effects of squalamine on M. smithii cell wall.(A) M. smithii without squalamine. (B) M. smithii +1 mg/L squalamine. White arrows show holes caused by squalamine on M. smithii cell wall. The scale bar corresponds to 500 nm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643942&req=5

pone-0062738-g003: Images by electron microscopy demonstrating the morphological effects of squalamine on M. smithii cell wall.(A) M. smithii without squalamine. (B) M. smithii +1 mg/L squalamine. White arrows show holes caused by squalamine on M. smithii cell wall. The scale bar corresponds to 500 nm.
Mentions: Two commonly used biocides chlorhexidine and peracetic acid, exhibited an archaeacidal activity under current decontamination protocols and by using concentrations of 0.2 and 1.5 g/L, respectively. However, squalamine and its derivatives exhibited a higher activity than these two usual biocides on the majority of here tested archaea, not on all archaea. Interestingly, these compounds are equally active against Gram-negative and Gram-positive bacteria, including bacteria from the human intestinal microbiota [17], [20]. They act directly on the cell membrane of the bacteria by creating holes (Figure 3), emptying the cell cytoplasms which lead to the death of the bacteria [17]. Data herein reported indicate that some squalamine derivatives exhibited an increased in-vitro activity against methanogenic archaea, particularly for derivative S1. Indeed, the structure of the different squalamine derivatives greatly influences their archaeacidal activity: aminosterol derivatives from dehydroepiandrosterone (DHEA) demonstrate a lower activity (around 5 µg/mL) compared to pregnenolone derivatives (0.05 to 0.5 µg/mL) while they differ only by the length of the side chain in position 17 suggesting a required specific conformation by targeting archaea. On the other hand, even in the same series the activity is conserved whatever the nature of the amino side chain introduced except for derivative S1 which is ten times more active and which differs only by the presence of three positive charges instead of two in all the other products suggesting a potent interaction of the positive charge of the compound with the negative charge of the archaeal membrane (Figure 1). All these features constitute a basis for the development of a new class of biocides devoted to the decontamination of archaea-contaminated medical devices.

Bottom Line: However, no biocide activity has been reported among these human-associated archaea.Squalamine derivative S1 exhibited a 10-200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea.As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Université, URMITE, UMR63 CNRS 7278, IRD 198, Inserm 1095, Marseille, France.

ABSTRACT

Background: Several methanogenic archaea have been detected in the human intestinal microbiota. These intestinal archaea may contaminate medical devices such as colonoscopes. However, no biocide activity has been reported among these human-associated archaea.

Methodology: The minimal archaeacidal concentration (MAC) of peracetic acid, chlorhexidine, squalamine and twelve parent synthetic derivatives reported in this study was determined against five human-associated methanogenic archaea including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanobrevibacter arboriphilicus, Methanosphaera stadtmanae, Methanomassiliicoccus luminyensis and two environmental methanogens Methanobacterium beijingense and Methanosaeta concilii by using a serial dilution technique in Hungates tubes.

Principal findings: MAC of squalamine derivative S1 was 0.05 mg/L against M. smithii strains, M. oralis, M. arboriphilicus, M. concilii and M. beijingense whereas MAC of squalamine and derivatives S2-S12 varied from 0.5 to 5 mg/L. For M. stadtmanae and M. luminyensis, MAC of derivative S1 was 0.1 mg/L and varied from 1 to ≥ 10 mg/L for squalamine and its parent derivatives S2-S12. Under the same experimental conditions, chlorhexidine and peracetic acid lead to a MAC of 0.2 and 1.5 mg/L, respectively against all tested archaea.

Conclusions/significance: Squalamine derivative S1 exhibited a 10-200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea. As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea.

Show MeSH
Related in: MedlinePlus