128 Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

Kim, Jae Gwan; Kim, Ki S.; Cheon, Won Seok; Kim, Jeong Wook

doi:10.1016/s0016-5085(09)60111-6

Cited by 3 publications

(6 citation statements)

References 21 publications

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“…S414R substitution, found in AMX-resistant isolates in different geographic areas, was absent in the isolates of this study and in those reported previously. 7,44…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance inHelicobacter pyloriIsolates from Buenos Aires City

Palma

Mendiondo

Wonaga³

et al. 2017

Microbial Drug Resistance

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Domain V of 23S rRNA, gyrA and gyrB Quinolones Resistance-Determining Region (QRDR), and pbp-1A gene point mutations were investigated in Helicobacter pylori-resistant isolates from three centres of Buenos Aires. Minimal inhibitory concentrations (MICs) were performed in 197 isolates from 52 H. pylori-positive naive patients by agar dilution method. Point mutations were achieved by amplification and sequencing of the target genes, and their association with resistance was determined by natural transformation assays. Resistance rates were as follows: metronidazole 28.8%, clarithromycin (CLA) 26.9%, levofloxacin (LEV) 32.7%, and amoxicillin (AMX) 7.6%. Nearly one-third of patients carried multidrug-resistant isolates. A2143G or A2142G in domain V of 23S-rRNA was found in all isolates showing high level of resistance to CLA (MIC >2 mg/L), accounting for 76.0% (38/50) of those with the resistant phenotype. The mutations A2267G or T1861C carried by 8/12 isolates with MIC 1-2 mg/L (low level) did not confer resistance by transformation. Substitutions at GyrA position 87 or 91, mainly N87K and D91G, were found in 92.8% (52/56) of the LEV-resistant isolates: 48 isolates with MIC 4-64 mg/L and 4/8 isolates with MIC 2 mg/L. The remaining four harboured K133N, also present in susceptible isolates. None of the substitutions in GyrB demonstrated to confer resistance. Transformation proved that PBP-1A N562Y and/or T556S substitutions confer the AMX resistance in our isolates, showing an additive effect. In conclusion, the usually reported mutations related to CLA, LEV, and AMX resistance were found in our isolates. However, low-level CLA resistance seems not to be due to mutations in Domain V of 23S rRNA gene.

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“…S414R substitution, found in AMX-resistant isolates in different geographic areas, was absent in the isolates of this study and in those reported previously. 7,44…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance inHelicobacter pyloriIsolates from Buenos Aires City

Palma

Mendiondo

Wonaga³

et al. 2017

Microbial Drug Resistance

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“…Based on published literature, 36‐43 seven polymorphisms in PBP1 that correlated with increased amoxicillin resistance were identified and then these mutations were engineered in G27; S417T, E406A, S414R, V374L, N562Y, T593A, and A599G. The constructed strains were then tested for amoxicillin resistance via E‐strip (Table 3).…”

Section: Resultsmentioning

confidence: 99%

“…To begin to understand the contribution of particular mutations to antibiotic resistance as well as to fitness, strains bearing defined isogenic mutations in rdxA and pbp1 were created. The mutations that were chosen for study were selected based on two criteria: (a) published literature suggesting that a particular mutation in rdxA 30‐35 or pbp1 36‐43 correlated with a high level of resistance to metronidazole or amoxicillin, respectively; and (b) this correlation must have also been identified in a different H. pylori strain. To this end, five sets of polymorphisms in RdxA were chosen for further study (Q50stop, N73stop, L62V S88P, R16H, and G98S) and seven sets of polymorphisms in PBP1 were selected (S417T, E406A, S414R, V374L, N562Y, T593A, and A599G).…”

Section: Resultsmentioning

confidence: 99%

“…However, Japan consumes far less amoxicillin 66 than Korea, Europe, and the Americas, 67‐71 so increased selective pressure cannot be the only explanation. Reports in the literature suggest that N562Y mutations are more prevalent in Korea and Japan; the N562Y mutation is found in 63.1% of amoxicillin‐resistant strains from Japan and Korea 37‐40,72 and in 14.3% of amoxicillin‐resistant strains from Europe and the Americas 36,41,73 . Given that diets in Korea and Japan contain a higher salt content 74,75 than in the west, 76,77 it is tempting to speculate that the local diet selects for mutations, like PBP1 N562Y, that result in an increased likelihood of surviving the high osmotic stress conditions imposed by the dietary salt.…”

Section: Discussionmentioning

confidence: 99%

“…Most mutations are silent, 29 but even if the amino acid is changed, the mutation might not alter gene function. While there are many studies that have identified clinical isolates of H. pylori that are resistant to metronidazole 30‐35 or amoxicillin 36‐43 and have identified corresponding changes in the sequences of rdxA or pbp1 , respectively, those studies often stop short of clearly defining the role of individual mutations in the associated resistance phenotypes by recreation of the mutation in a clean genetic background. Given this caveat, it is often unclear if a particular mutation alone can result in resistance.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of fitness costs associated with metronidazole and amoxicillin resistance in Helicobacter pylori

Windham

Merrell

2020

Helicobacter

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Background Increasing rates of antibiotic resistance are a major concern for all pathogens, including H. pylori. However, increased resistance often coincides with a decrease in relative fitness of the pathogen in the absence of the antibiotic, raising the possibility that increased resistance can be mitigated for some antibiotics by improved antibiotic husbandry. Therefore, a greater understanding of which types of antibiotic resistance create fitness defects in H. pylori may aid rational treatment strategies. Materials and Methods While a wealth of H. pylori literature reports mutations that correlate with increased resistance, few studies demonstrate causation for these same mutations. Herein, we examined fitness costs associated with metronidazole and amoxicillin resistance. Isogenic strains bearing literature reported point mutations in the rdxA and pbp1 genes were engineered and tested in in vitro competition assays to assess relative fitness. Results None of the metronidazole resistance mutations resulted in a fitness cost under the tested conditions. In contrast, amoxicillin‐resistant mutant strains demonstrated a defect in competition by 24 hours. This change in fitness was further enhanced by moderate osmotic stress. However, under extreme osmotic stress, the amoxicillin‐resistant N562Y PBP1 mutant strain showed enhanced fitness, suggesting that there are some pbp1 mutations that can give a conditional fitness advantage. Conclusions Our results demonstrate the role of specific point mutations in rdxA and pbp1 in antibiotic resistance and suggest that amoxicillin‐resistant strains of H. pylori show environmentally dictated changes in fitness. These later finding may be responsible for the relatively low rates of amoxicillin resistance seen in the United States.

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Hematological Changes Associated with Amoxicillin, Paracetamol and Their Combinations on Rabbits

2021

Integr J Vet Biosci

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Amoxicillin is a (2S,5R,6R)-6-[[(2R)-2-Amino-2-(4hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, semi-synthetic, acid stable drug belongs to a class of antibiotics called the Penicillins (B-lactam antibiotics). Materials and Methods ChemicalsAmoxicillin and Paracetamol (purity 99%) were obtained from Middle East Pharmaceutical and cosmetics laboratories Co .LTD. All other chemicals used in the experiment were purchased from standard commercial suppliers. Experimental AnimalsAdult male rabbits were purchased from locally certified farms. They were housed in a suitable room equipped with air conditioning according to US-EPA 2004 for a period of two weeks initially to acclimate to insure a stable experimental condition. The rabbits were properly maintained according to the principles and guidelines issued by the Ministry of Agriculture in Gaza And US-EPA2004 for animal care, rabbits were individually placed in appropriate steel cages at 22-26°C, 40-70% humidity and a clean environment with a light/12 hour cycle. A suitable diet of balanced feed and clean water has been provided for the duration of the total experiment.

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128 Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

Cited by 3 publications

References 21 publications

Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance inHelicobacter pyloriIsolates from Buenos Aires City

Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance inHelicobacter pyloriIsolates from Buenos Aires City

Analysis of fitness costs associated with metronidazole and amoxicillin resistance in Helicobacter pylori

Hematological Changes Associated with Amoxicillin, Paracetamol and Their Combinations on Rabbits

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