Biofilms: Microbial Shelters Against Antibiotics

Hathroubi, Skander; Mekni, Mohamed Amine; Domenico, Philip; Nguyen, Dao M.; Jacques, Mario

doi:10.1089/mdr.2016.0087

Cited by 136 publications

(108 citation statements)

References 153 publications

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“…It is well known that bacteria within biofilm can be 10 to 10,000 times more tolerant to antibiotics than their planktonic counterparts (Hoiby, Bjarnsholt et al 2010, Stewart 2015, Hathroubi, Mekni et al 2017). However, the impact of biofilm mode of growth on susceptibility to antimicrobial agents in H. pylori has not been well documented.…”

Section: Biofilm Cells Demonstrate High Levels Of Antibiotic Tolerancmentioning

confidence: 99%

“…Biofilms can constitute a physical and/or chemical diffusion barriers to antimicrobial penetration (Stewart 2015, Hathroubi, Mekni et al 2017. H. pylori is known to use a matrix composed mainly of eDNA and proteins (Grande, Di Giulio et al 2011, Grande, Di Marcantonio et al 2015, Hathroubi, Zerebinski et al 2018.…”

Section: Biofilm Matrix-associated Protein Restrict Clarithromycin Pementioning

confidence: 99%

“…Within a biofilm, cells are often highly resistant to environmental stress, as well as recalcitrant to the action of antibiotics and the host immune system. These properties make biofilm growth one of the major global challenges to modern medicine (Costerton, Stewart et al 1999, Hathroubi, Mekni et al 2017.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant

Hathroubi

Zerebinski

Ottemann

2019

Preprint

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Biofilm growth protects bacteria against harsh environments, antimicrobials, and immune responses. Helicobacter pylori is a bacterium that has a robust ability to maintain colonization in a challenging environment. Over the last decade, H. pylori biofilm formation has begun to be characterized, however, there are still gaps in our understanding about how this growth mode is defined and its impact on H. pylori physiology. To provide insights into H. pylori biofilm growth properties, we characterized the antibiotic susceptibility, gene expression, and genes required for biofilm formation of a strong biofilm-producing H. pylori. H. pylori biofilms developed complex 3D structures and were recalcitrant to multiple antibiotics. Disruption of the protein-based matrix decreased this antibiotic tolerance. Using both transcriptomic and genomic approaches, we discovered that biofilm cells demonstrated lower transcripts for TCA cycle enzymes but higher ones for hydrogenase and acetone metabolism. Interestingly, several genes encoding for the natural competence Type IV secretion system 4 (tfs4) were up-regulated during biofilm formation along with several genes encoding for restriction-modification (R-M) systems, suggesting DNA exchange activities in this mode of growth. Flagella genes were also discovered through both approaches, consistent with previous reports about the importance of these filaments in H. pylori biofilm. Together, these data suggest that H. pylori is capable of adjusting its phenotype when grown as biofilm, changing its metabolism and elevating specific surface proteins including those encoding tfs4 and flagella.

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Section: Biofilm Cells Demonstrate High Levels Of Antibiotic Tolerancmentioning

confidence: 99%

Section: Biofilm Matrix-associated Protein Restrict Clarithromycin Pementioning

confidence: 99%

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Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant

Hathroubi

Zerebinski

Ottemann

2019

Preprint

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“…Biofilms are dense aggregates of microorganisms attached to a surface and embedded in an extracellular polymeric matrix (14). In contrast with the other mode of bacterial growth, free-floating or planktonic, biofilm cells tend to be more tolerant towards antimicrobials and host immune responses (14,15). Biofilms are also frequently associated with chronic disease including pneumonia in cystic fibrosis patients, Lyme disease, and chronic otitis media (16-18).…”

Section: Introductionmentioning

confidence: 99%

The Helicobacter pylori biofilm involves a multi-gene stress-biased response including a structural role for flagella

Hathroubi

Zerebinski

Ottemann

2018

Preprint

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Helicobacter pylori has an impressive ability to persist chronically in the human stomach. Similar characteristics are associated with biofilm formation in other bacteria. The H. pylori biofilm process, however, is poorly understood. To gain insight into this mode of growth, we carried out comparative transcriptomic analysis between H. pylori biofilm and planktonic cells, using the mouse colonizing strain SS1. Optimal biofilm formation was obtained with low serum and three-day growth, conditions which caused both biofilm and planktonic cells to be ∼80% coccoid. RNA-seq analysis found that 8.18% of genes were differentially expressed between biofilm and planktonic cell transcriptomes. Biofilm-downregulated genes included those involved in metabolism and translation, suggesting these cells have low metabolic activity. Biofilm-upregulated genes included those whose products were predicted to be at the cell envelope, involved in regulating a stress response, and surprisingly, genes related to formation of the flagellar apparatus. Scanning electron microscopy visualized flagella that appeared to be a component of the biofilm matrix, supported by the observation that an aflagellated mutant displayed a less robust biofilm with no apparent filaments. We observed flagella in the biofilm matrix of additional H. pylori strains, supporting that flagellar use is widespread. Our data thus supports a model in which H. pylori biofilm involves a multi-gene stress-biased response, and that flagella play an important role in H. pylori biofilm formation.IMPORTANCEBiofilms, communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances, pose a substantial health risk and are key contributors to many chronic and recurrent infections. Chronicity and recalcitrant infections are also common features associated with the ulcer-causing human pathogen H. pylori. However, relatively little is known about the role of biofilms in H. pylori pathogenesis as well as the biofilm structure itself and the genes associated with this mode of growth. In the present study, we found that H. pylori biofilm cells highly expressed genes related to cell envelope, stress response and those encoding the flagellar apparatus. Flagellar filaments were seen in high abundance in the biofilm. Flagella are known to play a role in initial biofilm formation, but typically are downregulated after that state. H. pylori instead appears to have co-opted these structures for non-motility roles, including a role building a robust biofilm.

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“…Biofilms contribute to the development antibiotic tolerance and resistance [17][18][19] . Biofilms form a physical barrier to many antibiotics, restricting effective drug concentrations to sub-lethal levels and promoting the outgrowth of resistant strains 20 . They also block host immune responses, protecting cells from phagocytosis and complement mediated killing [21][22][23] .…”

mentioning

confidence: 99%

Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli

et al. 2020

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Bacterial biofilms, especially those associated with implanted medical devices, are difficult to eradicate. Curli amyloid fibers are important components of the biofilms formed by the Enterobacteriaceae family. Here, we show that a human monoclonal antibody with panamyloid-binding activity (mAb 3H3) can disrupt biofilms formed by Salmonella enterica serovar Typhimurium in vitro and in vivo. The antibody disrupts the biofilm structure, enhancing biofilm eradication by antibiotics and immune cells. In mice, 3H3 injections allow antibioticmediated clearance of catheter-associated S. Typhimurium biofilms. Thus, monoclonal antibodies that bind a pan-amyloid epitope have potential to prevent or eradicate bacterial biofilms.

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Biofilms: Microbial Shelters Against Antibiotics

Cited by 136 publications

References 153 publications

Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant

Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant

The Helicobacter pylori biofilm involves a multi-gene stress-biased response including a structural role for flagella

Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli

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