Transformation of Helicobacter pylori into Coccoid Forms as a Challenge for Research Determining Activity of Antimicrobial Substances

Krzyżek, Paweł; Grande, Rossella

doi:10.3390/pathogens9030184

Cited by 32 publications

(42 citation statements)

References 92 publications

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“…It also bears noting that recent research has found that H. pylori can sometimes transform from the expected spiral form to a coccoid form, which could result in an inaccurate AST if the bacteria are in a viable-but-nonculturable state. This transformation could result in treatment failure without the presence of ARGs, further complicating the picture of AMR in H. pylori [ 39 ]. While WGS may be useful in overcoming the limitations of studies by allowing analysis of the full resistome, the relative contribution of each mutation to the MIC as well as the effect of combinations of mutations and shape transformation remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori

et al. 2020

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Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli H. pylori isolates (n = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our in-house bioinformatics pipeline targeting point mutations in the relevant genes (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in H. pylori cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of H. pylori isolates demonstrates that inferring resistance phenotypes from WGS in H. pylori remains challenging and should be optimized further.

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Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori

et al. 2020

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“…The impact of 3-BP and SER has been extended to assess morphological changes in H. pylori , a process for which an involvement in antibiotic tolerance is suggested [ 56 , 57 ]. Bacteria treated with these substances underwent morphological transition to spherical cells ( Figure 3 and Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon seems to be particularly interesting in the case of AMX, because this antibiotic had a very high bactericidal activity against planktonic forms (a microdilution method, MIC = 0.06–0.12 µg/mL) and freshly seeded cells settled on the agar (growth inhibition zones produced by 25 µg/disk being ~60 mm), while significantly lower in relation to 3 day-old, lawn H. pylori biofilms (reduction of CFU/mL after a 4-h incubation was <3 logs). A high level of green fluorescence suggests that the observed decrease in CFU/mL is rather associated with the loss of culturability in the process of transformation into coccoid forms than the reduction of viability [ 57 ]. Our observations are consistent with the reports of others indicating a low bactericidal activity of AMX against biofilm H. pylori forms [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight against Helicobacter pylori Lawn Biofilm

Krzyżek

Gościniak

Fijałkowski

et al. 2020

IJMS

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Helicobacter pylori is a bacterium known mainly of its ability to cause persistent inflammations of the human stomach, resulting in peptic ulcer diseases and gastric cancers. Continuous exposure of this bacterium to antibiotics has resulted in high detection of multidrug-resistant strains and difficulties in obtaining a therapeutic effect. The purpose of the present study was to determine the usability of bacterial cellulose (BC) chemisorbed with 3-bromopyruvate (3-BP) or sertraline (SER) to act against lawn H. pylori biofilms. The characterization of BC carriers was made using a N2 adsorption/desorption analysis, tensile strength test, and scanning electron microscopy (SEM) observations. Determination of an antimicrobial activity was performed using a modified disk-diffusion method and a self-designed method of testing antibacterial activity against biofilm microbial forms. In addition, bacterial morphology was checked by SEM. It was found that BC disks were characterized by a high cross-linking and shear/stretch resistance. Growth inhibition zones for BC disks chemisorbed with 2 mg of SER or 3-BP were equal to 26.5–27.5 mm and 27–30 mm, respectively. The viability of lawn biofilm H. pylori cells after a 4-h incubation with 2 mg SER or 3-BP chemisorbed on BC disks was ≥4 log lower, suggesting their antibacterial effect. SEM observations showed a number of morphostructural changes in H. pylori cells exposed to these substances. Concluding, SER and 3-BP chemisorbed on BC carriers presented a promising antibacterial activity against biofilm H. pylori cells in in vitro conditions.

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“…Nowadays, however, an alarmingly high detection of multidrug-resistant (MDR) H. pylori strains is observed [ 8 ]. Factors associated with the appearance of MDR strains include antibiotic abuse, therapeutic failures, and phenotypical mechanisms promoting resistance/tolerance of these bacteria to antimicrobial substances (efflux pumps expression, biofilm formation, or morphological transformation) [ 9 , 10 , 11 , 12 ]. High prevalence, carcinogenic potential, and ability of dynamic resistance spreading constituted the premise for including H. pylori in the list of twelve priority pathogens and the need to search for new methods eradicating this microorganism [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Therapies as a Promising Option for the Treatment of Antibiotic-Resistant Helicobacter pylori

2020

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Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.

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Transformation of Helicobacter pylori into Coccoid Forms as a Challenge for Research Determining Activity of Antimicrobial Substances

Cited by 32 publications

References 92 publications

Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori

Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori

Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight against Helicobacter pylori Lawn Biofilm

Synergistic Therapies as a Promising Option for the Treatment of Antibiotic-Resistant Helicobacter pylori

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