The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin.
Boo Shan Tseng,Wei Zhang,Joe J. Harrison,Tam P. Quach,Jisun L. Song,Jon Penterman,Jon Penterman,Pradeep K. Singh,David L. Chopp,Aaron I. Packman,Matthew R. Parsek +10 more
TLDR
It is proposed that tobramycin sequestration at the biofilm periphery is an important mechanism in protecting metabolically active cells that lie just below the zone of sequestration.Abstract:
Biofilm cells are less susceptible to antimicrobials than their planktonic counterparts. While this phenomenon is multifactorial, the ability of the matrix to reduce antibiotic penetration into the biofilm is thought to be of limited importance studies suggest that antibiotics move fairly rapidly through biofilms. In this study, we monitored the transport of two clinically relevant antibiotics, tobramycin and ciprofloxacin, into non-mucoid Pseudomonas aeruginosa biofilms. To our surprise, we found that the positively charged antibiotic tobramycin is sequestered to the biofilm periphery, while the neutral antibiotic ciprofloxacin readily penetrated. We provide evidence that tobramycin in the biofilm periphery both stimulated a localized stress response and killed bacteria in these regions but not in the underlying biofilm. Although it is unclear which matrix component binds tobramycin, its penetration was increased by the addition of cations in a dose-dependent manner, which led to increased biofilm death. These data suggest that ionic interactions of tobramycin with the biofilm matrix limit its penetration. We propose that tobramycin sequestration at the biofilm periphery is an important mechanism in protecting metabolically active cells that lie just below the zone of sequestration.read more
Citations
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Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria
Clayton W. Hall,Thien-Fah Mah +1 more
TL;DR: This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms and suggestions for future work in the field are provided.
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Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics
TL;DR: This review presents the current understanding of the molecular mechanisms of biofilm recalcitrance toward antibiotics and describes how recent progress has improved the capacity to design original and efficient strategies to prevent or eradicate biofilm-related infections.
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Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention
TL;DR: A brief overview of concepts of bacterial biofilm formation, current state-of-the-art therapeutic approaches for preventing and treating biofilms, and the prevalence of such infections on medical devices is reviewed.
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Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections
Jessa Marie Makabenta,Ahmed Nabawy,Cheng-Hsuan Li,Suzannah M. Schmidt-Malan,Robin Patel,Vincent M. Rotello +5 more
TL;DR: The mechanisms by which nanomaterials can be used to target antibiotic-resistant bacterial infections are discussed, design elements and properties of nanomMaterials that can be engineered to enhance potency are highlighted, and recent progress and remaining challenges for clinical implementation are explored.
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Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms
TL;DR: Three mechanisms that play an important role in biofilm survival are discussed, found both in bacterial and fungal biofilms and are often surprisingly similar between distantly related organisms.
References
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The Pel Polysaccharide Can Serve a Structural and Protective Role in the Biofilm Matrix of Pseudomonas aeruginosa
Kelly M. Colvin,Vernita Gordon,Keiji Murakami,Bradley R. Borlee,Daniel J. Wozniak,Gerard C. L. Wong,Matthew R. Parsek +6 more
TL;DR: It is shown that expression of the pel gene cluster and PelF protein levels are enhanced during biofilm growth compared to liquid cultures, suggesting that Pel is capable of playing both a structural and a protective role in P. aeruginosa biofilms.
Journal ArticleDOI
A Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms
TL;DR: Contribution of the MDR-mediated efflux to antibiotic resistance of Pseudomonas aeruginosa biofilms was examined by using strains overexpressing and lacking the MexAB-OprM pump, and dose-dependent killing indicated the presence of a small “superresistant” cell fraction.
Journal ArticleDOI
Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms.
Daniel J. Wozniak,Timna J. O. Wyckoff,Melissa Starkey,Rebecca Keyser,Parastoo Azadi,George A. O'Toole,Matthew R. Parsek +6 more
TL;DR: The results clearly indicate that alginate biosynthetic genes are not expressed and thatAlginate is not required during the formation of nonmucoid biofilms in two P. aeruginosa strains, PAO1 and PA14, that have traditionally been used to study biofilmms.
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The Pel and Psl polysaccharides provide Pseudomonas aeruginosa structural redundancy within the biofilm matrix
Kelly M. Colvin,Yasuhiko Irie,Catherine S. Tart,Rodolfo Urbano,John C. Whitney,Cynthia Ryder,P. Lynne Howell,Daniel J. Wozniak,Matthew R. Parsek +8 more
TL;DR: This study evaluated a range of clinical and environmental P.aeruginosa isolates for their dependence on Pel and Psl for biofilm development and revealed both unique and redundant roles for two distinct biofilm exopolysaccharides.
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Oxygen Limitation Contributes to Antibiotic Tolerance of Pseudomonas aeruginosa in Biofilms
Giorgia Borriello,Erin M. Werner,Frank L. Roe,Aana M. Kim,Garth D. Ehrlich,Philip S. Stewart +5 more
TL;DR: Results show that 48-h-old colony biofilms are physiologically heterogeneous and that most of the cells in the biofilm occupy an oxygen-limited, stationary-phase state, and that when 4- h-old colonies were challenged under anaerobic conditions, the level of killing by antibiotics was reduced compared to that for the controls grown aerobically.