Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the
            <i>Pseudomonas aeruginosa</i>
            biofilm matrix

Jennings, Laura K.; Storek, Kelly M.; Ledvina, Hannah E.; Coulon, Charlène; Marmont, Lindsey S.; Sadovskaya, Irina; Secor, Patrick R.; Tseng, Boo Shan; Scian, Michele; Filloux, Alain; Wozniak, Daniel J.; Howell, P. Lynne; Parsek, Matthew R.

doi:10.1073/pnas.1503058112

Cited by 520 publications

(605 citation statements)

References 43 publications

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“…Psl and Pel are often associated with nonmucoid strains and are necessary for biofilm formation (34). The anionic alginate could interact electrostatically with Bac7(1-35) enhancing the binding of the peptide, while the cationic Pel could repulse it (35). In this respect, it has been shown that alginate in solution inhibits the antimicrobial activity of structurally different peptides, including Bac7(1-35) (36).…”

Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

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Pseudomonas aeruginosa infections represent a serious threat to worldwide health. Proline-rich antimicrobial peptides (PR-AMPs), a particular group of peptide antibiotics, have demonstrated in vitro activity against P. aeruginosa strains. Here we show that the mammalian PR-AMP Bac7(1-35) is active against some multidrug-resistant cystic fibrosis isolates of P. aeruginosa. By confocal microscopy and cytometric analyses, we investigated the mechanism of killing against P. aeruginosa strain PAO1 and three selected isolates, and we observed that the peptide inactivated the target cells by disrupting their cellular membranes. This effect is deeply different from that previously described for PR-AMPs in Escherichia coli and Salmonella enterica serovar Typhimurium, where these peptides act intracellularly after having been internalized by means of the transporter SbmA without membranolytic effects. The heterologous expression of SbmA in PAO1 cells enhanced the internalization of Bac7(1-35) into the cytoplasm, making the bacteria more susceptible to the peptide but at the same time more resistant to the membrane lysis, similarly to what occurs in E. coli. The results evidenced a new mechanism of action for PRAMPs and indicate that Bac7 has multiple and variable modes of action that depend on the characteristics of the different target species and the possibility to be internalized by bacterial transporters. This feature broadens the spectrum of activity of the peptide and makes the development of peptide-resistant bacteria a more difficult process.

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Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

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“…In comparison, P. aeruginosa has the genetic capacity to produce three biofilm exopolysaccharides: alginate, Psl and Pel (16). GAG shares several similarities with Pel, which has been identified as a cationic heteroglycan composed of 1,4-linked GalNAc and N-acetyl-D-glucosamine (GlcNAc) (17). Like GAG, the cationic nature of Pel results from partial deacetylation of the polymer (17).…”

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confidence: 99%

“…GAG shares several similarities with Pel, which has been identified as a cationic heteroglycan composed of 1,4-linked GalNAc and N-acetyl-D-glucosamine (GlcNAc) (17). Like GAG, the cationic nature of Pel results from partial deacetylation of the polymer (17). Most clinical and environmental isolates of P. aeruginosa use Pel and Psl during biofilm formation (18).…”

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confidence: 99%

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity

Snarr

Baker

Bamford

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-D-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3 h from A. fumigatus and PelA h from P. aeruginosa) were found to degrade their respective polysaccharides in vitro. We therefore hypothesized that these glycoside hydrolases could exhibit antibiofilm activity and, further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment of A. fumigatus with Sph3 h disrupted A. fumigatus biofilms with an EC 50 of 0.4 nM. PelA h treatment also disrupted preformed A. fumigatus biofilms with EC 50 values similar to those obtained for Sph3 h . In contrast, Sph3 h was unable to disrupt P. aeruginosa Pel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment of A. fumigatus hyphae with either Sph3 h or PelA h significantly enhanced the activity of the antifungals posaconazole, amphotericin B, and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were noncytotoxic and protected A549 pulmonary epithelial cells from A. fumigatus-induced cell damage for up to 24 h. Intratracheal administration of Sph3 h was well tolerated and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.biofilm | Aspergillus | Pseudomonas | therapeutics | exopolysaccharide

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“…Further, it was recently shown that the presence of a filamentous bacteriophage can result in conversion of the matrix into liquid crystalline structure, which is linked to antibiotic resistance and the physical stability of the biofilm matrix (Secor et al ., 2015). As the matrix components are identified, it may be possible to develop specific visualization approaches, such as the Wisteria floribunda lectin that specifically recognizes the Pel polysaccharide (Jennings et al ., 2015), so that the localization and interactions between EPS components can be studied. This may also help explain why the biofilm is more than the sum of its individual parts.…”

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confidence: 99%

Next‐generation studies of microbial biofilm communities

Rice

Wuertz

Kjelleberg

2016

Microbial Biotechnology

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SummaryAs we look into the future of microbial biofilm research, there is clearly an emerging focus on communities rather than populations. This represents an essential change in direction to more accurately understand how and why microorganisms assemble into communities, as well as the functional implications for such a life style. For example, current research studies shows that communities display emergent properties or functions that are not predicted from the individual single species populations, including elevated stress tolerance and resistance to antibiotics. Models for mixed species biofilms can be very simple, comprised only a handful of species or can be extremely species rich, with hundreds or thousands of species present. The future holds much promise for this area of research, where investigators will increasingly be able to resolve, at the molecular and biochemical levels, interspecies relationships and mechanisms of interaction. The outcome of these studies will greatly enhance our understanding of the ecological and evolutionary factors that drive community function in natural and engineered systems.

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Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix

Cited by 520 publications

References 43 publications

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity

Next‐generation studies of microbial biofilm communities

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