Helicobacter pylori Biofilm and New Strategies to Combat it

2020 ◽  
Vol 20 ◽  
Author(s):  
Majid Taati Moghadam ◽  
Zahra Chegini ◽  
Amin Khoshbayan ◽  
Iman Farahani ◽  
Aref Shariati
Keyword(s):  
Helicobacter Pylori ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Combination Therapies ◽  
Chronic Infections ◽  
Chemical Substances ◽  
And Performance ◽  
H Pylori ◽  
Initial Binding ◽  
New Strategies

: Helicobacter pylori, the most frequent pathogens worldwide that colonize around 50% of the world’s population, cause important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to the eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.

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

2018 ◽  
Author(s):  
Skander Hathroubi ◽  
Julia Zerebinski ◽  
Karen M. Ottemann
Keyword(s):  
Helicobacter Pylori ◽  
Stress Response ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Cell Envelope ◽  
Flagellar Apparatus ◽  
Growth Conditions ◽  
Planktonic Cells ◽  
H Pylori ◽  
Biofilm Matrix

AbstractHelicobacter 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.

scholarly journals Helicobacter pylori Biofilm Involves a Multigene Stress-Biased Response, Including a Structural Role for Flagella

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Skander Hathroubi ◽  
Julia Zerebinski ◽  
Karen M. Ottemann
Keyword(s):  
Helicobacter Pylori ◽  
Stress Response ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Cell Envelope ◽  
Flagellar Apparatus ◽  
Planktonic Cells ◽  
Content Type ◽  
H Pylori ◽  
Biofilm Matrix

ABSTRACT 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 a low concentration of serum and 3 days of growth, conditions that caused both biofilm and planktonic cells to be ∼80% coccoid. Transcriptome sequencing (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 support a model in which H. pylori biofilm involves a multigene stress-biased response and that flagella play an important role in H. pylori biofilm formation. IMPORTANCE Biofilms, 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 and stress response, as well as 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 coopted these structures for nonmotility roles, including a role building a robust biofilm.

scholarly journals Myricetin as an Antivirulence Compound Interfering with a Morphological Transformation into Coccoid Forms and Potentiating Activity of Antibiotics against Helicobacter pylori

2021 ◽  
Vol 22 (5) ◽  
pp. 2695
Author(s):  
Paweł Krzyżek ◽  
Paweł Migdał ◽  
Emil Paluch ◽  
Magdalena Karwańska ◽  
Alina Wieliczko ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Biofilm Formation ◽  
Inhibitory Effect ◽  
Morphological Transformation ◽  
High Tendency ◽  
Minimal Inhibitory Concentrations ◽  
Coccoid Form ◽  
Stomach Diseases ◽  
Fold Reduction ◽  
H Pylori

Helicobacter pylori, a gastric pathogen associated with a broad range of stomach diseases, has a high tendency to become resistant to antibiotics. One of the most important factors related to therapeutic failures is its ability to change from a spiral to a coccoid form. Therefore, the main aim of our original article was to determine the influence of myricetin, a natural compound with an antivirulence action, on the morphological transformation of H. pylori and check the potential of myricetin to increase the activity of antibiotics against this pathogen. We observed that sub-minimal inhibitory concentrations (sub-MICs) of this compound have the ability to slow down the process of transformation into coccoid forms and reduce biofilm formation of this bacterium. Using checkerboard assays, we noticed that the exposure of H. pylori to sub-MICs of myricetin enabled a 4–16-fold reduction in MICs of all classically used antibiotics (amoxicillin, clarithromycin, tetracycline, metronidazole, and levofloxacin). Additionally, RT-qPCR studies of genes related to the H. pylori morphogenesis showed a decrease in their expression during exposure to myricetin. This inhibitory effect was more strongly seen for genes involved in the muropeptide monomers shortening (csd3, csd6, csd4, and amiA), suggesting their significant participation in the spiral-to-coccoid transition. To our knowledge, this is the first research showing the ability of any compound to synergistically interact with all five antibiotics against H. pylori and the first one showing the capacity of a natural substance to interfere with the morphological transition of H. pylori from spiral to coccoid forms.

scholarly journals Serology Is More Sensitive Than Urea Breath Test or Stool Antigen for the Initial Diagnosis of Helicobacter pylori Gastritis When Compared With Histopathology

2020 ◽  
Vol 154 (2) ◽  
pp. 255-265
Author(s):  
Dustin E Bosch ◽  
Niklas Krumm ◽  
Mark H Wener ◽  
Matthew M Yeh ◽  
Camtu D Truong ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Access To Care ◽  
Breath Test ◽  
Diagnostic Error ◽  
Urea Breath Test ◽  
Positive Serology ◽  
Noninvasive Test ◽  
Stool Antigen ◽  
And Performance ◽  
H Pylori

Abstract Objectives To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error. Methods H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence. Results Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error. Conclusions Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations.

scholarly journals Biofilm Formation and Antibiotic Resistance Phenotype of Helicobacter pylori Clinical Isolates

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 473 ◽  
Author(s):  
Kartika Afrida Fauzia ◽  
Muhammad Miftahussurur ◽  
Ari Fahrial Syam ◽  
Langgeng Agung Waskito ◽  
Dalla Doohan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Crystal Violet ◽  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
Clinical Isolates ◽  
Resistance Phenotype ◽  
Resistance To Antibiotics ◽  
Inhibition Concentration ◽  
H Pylori

We evaluated biofilm formation of clinical Helicobacter pylori isolates from Indonesia and its relation to antibiotic resistance. We determined the minimum inhibition concentration (MIC) of amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline by the Etest to measure the planktonic susceptibility of 101 H. pylori strains. Biofilms were quantified by the crystal violet method. The minimum biofilm eradication concentration (MBEC) was obtained by measuring the survival of bacteria in a biofilm after exposure to antibiotics. The majority of the strains formed a biofilm (93.1% (94/101)), including weak (75.5%) and strong (24.5%) biofilm-formers. Planktonic resistant and sensitive strains produced relatively equal amounts of biofilms. The resistance proportion, shown by the MBEC measurement, was higher in the strong biofilm group for all antibiotics compared to the weak biofilm group, especially for clarithromycin (p = 0.002). Several cases showed sensitivity by the MIC measurement, but resistance according to the MBEC measurements (amoxicillin, 47.6%; tetracycline, 57.1%; clarithromycin, 19.0%; levofloxacin, 38.1%; and metronidazole 38.1%). Thus, biofilm formation may increase the survival of H. pylori and its resistance to antibiotics. Biofilm-related antibiotic resistance should be evaluated with antibiotic susceptibility.

scholarly journals Nanoscale Structural and Mechanical Properties of Nontypeable Haemophilus influenzae Biofilms

2009 ◽  
Vol 191 (8) ◽  
pp. 2512-2520 ◽  
Author(s):  
Fernando Terán Arce ◽  
Ross Carlson ◽  
James Monds ◽  
Richard Veeh ◽  
Fen Z. Hu ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Single Molecule ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Single Cells ◽  
Turgor Pressure ◽  
Outer Cell ◽  
Nontypeable Haemophilus Influenzae ◽  
Chronic Infections ◽  
Pathogenic Factors

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) bacteria are commensals in the human nasopharynx, as well as pathogens associated with a spectrum of acute and chronic infections. Two important factors that influence NTHI pathogenicity are their ability to adhere to human tissue and their ability to form biofilms. Extracellular polymeric substances (EPS) and bacterial appendages such as pili critically influence cell adhesion and intercellular cohesion during biofilm formation. Structural components in the outer cell membrane, such as lipopolysaccharides, also play a fundamental role in infection of the host organism. In spite of their importance, these pathogenic factors are not yet well characterized at the nanoscale. Here, atomic force microscopy (AFM) was used in aqueous environments to visualize structural details, including probable Hif-type pili, of live NTHI bacteria at the early stages of biofilm formation. Using single-molecule AFM-based spectroscopy, the molecular elasticities of lipooligosaccharides present on NTHI cell surfaces were analyzed and compared between two strains (PittEE and PittGG) with very different pathogenicity profiles. Furthermore, the stiffness of single cells of both strains was measured and subsequently their turgor pressure was estimated.

scholarly journals Genetic Determinants of Biofilm Formation and Antibiotic Resistance of Helicobacter Pylori using Whole Genome Sequencing

2021 ◽  
Author(s):  
Kartika Afrida Fauzia ◽  
Hafeza Aftab ◽  
Muhammad Miftahussurur ◽  
Langgeng Agung Waskito ◽  
Vo Phuoc Tuan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Biofilm Formation ◽  
Cross Sectional Study ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Genome Sequences ◽  
Cross Sectional ◽  
H Pylori

Abstract The nucleotide polymorphisms (SNPs) associated with the biofilm formation phenotype of Helicobacter pylori were investigated. Fifty-six H. pylori isolates from Bangladeshi patients were included in this cross-sectional study. Crystal violet was used to classify the phenotypes into high- and low-biofilm formers. Whole genome sequences were analyzed using the “Antimicrobial Resistance Identification By Assembly” (ARIBA) pipeline. The results indicated 19.6% high- and 81.4% low-biofilm formers. These phenotypes were not related to specific clades in the phylogenetic analysis. Biofilm formation was significantly associated with SNPs of alpA, alpB, cagE, cgt, csd4, csd5, futB, gluP, homD, and murF (P < 0.05). Among the SNPs reported in alpB, strains encoding the N156K, G160S, and A223V mutations were high-biofilm formers. Mutations associated with antibiotic resistance can be detected. This study revealed the potential role of SNPs to biofilm formation, and propose a method to detect mutation in antibiotic resistance and biofilm from whole genome sequences.

scholarly journals Biological characteristics and virulence of Helicobacter pylori

2018 ◽  
Vol 20 (1) ◽  
pp. 14-23 ◽  
Author(s):  
G.Sh. Isaeva ◽  
R.I. Valieva
Keyword(s):  
Helicobacter Pylori ◽  
Clinical Outcomes ◽  
Genetic Heterogeneity ◽  
Biofilm Formation ◽  
Clinical Manifestations ◽  
Epidemiological Studies ◽  
Biological Characteristics ◽  
Pathogenicity Factors ◽  
H Pylori

This review summarizes the most recent data on the biological characteristics of Helicobacter pylori (morphological, cultural, biochemical). H. pylori pathogenicity factors promoting colonization, adhesion, biofilm formation, aggression, and cytotoxicity, their contribution to the pathogenesis of diseases as well as the possible relationships with various clinical outcomes are described in detail. The genetic heterogeneity of H. pylori strains which can determine different clinical manifestations and have significance for conducting epidemiological studies is also considered.

scholarly journals Genetic requirements and transcriptomics of Helicobacter pylori biofilm formation on abiotic and biotic surfaces

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Skander Hathroubi ◽  
Shuai Hu ◽  
Karen M. Ottemann
Keyword(s):  
Helicobacter Pylori ◽  
Biofilm Formation ◽  
Tca Cycle ◽  
Harsh Environments ◽  
Laboratory Model ◽  
Secretion Systems ◽  
Biofilm Growth ◽  
Tca Cycle Enzymes ◽  
Growth Properties ◽  
H Pylori

AbstractBiofilm growth is a widespread mechanism that protects bacteria against harsh environments, antimicrobials, and immune responses. These types of conditions challenge chronic colonizers such as Helicobacter pylori but it is not fully understood how H. pylori biofilm growth is defined and its impact on H. pylori survival. To provide insights into H. pylori biofilm growth properties, we characterized biofilm formation on abiotic and biotic surfaces, identified genes required for biofilm formation, and defined the biofilm-associated gene expression of the laboratory model H. pylori strain G27. We report that H. pylori G27 forms biofilms with a high biomass and complex flagella-filled 3D structures on both plastic and gastric epithelial cells. Using a screen for biofilm-defective mutants and transcriptomics, we discovered that biofilm cells demonstrated lower transcripts for TCA cycle enzymes but higher ones for flagellar formation, two type four secretion systems, hydrogenase, and acetone metabolism. We confirmed that biofilm formation requires flagella, hydrogenase, and acetone metabolism on both abiotic and biotic surfaces. Altogether, these data suggest that H. pylori is capable of adjusting its phenotype when grown as biofilm, changing its metabolism, and re-shaping flagella, typically locomotion organelles, into adhesive structures.

scholarly journals Isolation and Characterization of Tetracycline-Resistant Clinical Isolates of Helicobacter pylori

2000 ◽  
Vol 44 (11) ◽  
pp. 3203-3205 ◽  
Author(s):  
Dong H. Kwon ◽  
J. J. Kim ◽  
M. Lee ◽  
Y. Yamaoka ◽  
M. Kato ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Combination Therapies ◽  
Isolation And Characterization ◽  
The Cross ◽  
H Pylori

ABSTRACT Tetracycline is an important component of combination therapies forHelicobacter pylori eradication. Twenty-nine tetracycline-resistant isolates requiring MICs ranging from 4 to 16 μg/ml were isolated from Korean (22 of 460) and Japanese (7 of 105) patients. Interestingly, all of the 29 tetracycline-resistant isolates exhibited cross-resistance to metronidazole, and the cross-resistance was transferred to tetracycline-sensitive H. pylori strains.

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