Point Mutations at gyrA and gyrB Genes of Levofloxacin-Resistant Helicobacter pylori Isolates in the Esophageal Mucosa from a Venezuelan Population

Mariela López-Gasca Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela

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Jessy Peña Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela

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María-Alexandra García-Amado Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela

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Fabián Michelangeli Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela

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Monica Contreras Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela

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The treatment of Helicobacter pylori infection is complicated by antibiotic resistance. A high levofloxacin (LVX) resistance rate was previously demonstrated in H. pylori isolates from gastric mucosa (40%) and esophagus (19%) in individual hosts of a Venezuelan population. We aimed to assess the molecular mechanisms of LVX resistance and susceptibility in isolates from the gastroesophageal mucosa, by studying point mutations in the quinolone resistance–determining region of gyrA and gyrB genes. Sequencing of gyrA and gyrB genes (N = 120) helped to identify point mutations in 60 isolates (30 from antrum and 30 from esophagus) of five dyspeptic patients. Double (Asn87Thr and Asp91Asn) and single (Asn87Ile or Asn87Thr) mutations in the gyrA gene were identified in the esophageal mucosa. These mutations have been commonly found in the stomach. Occurrence of a single (Asn87Ile) mutation was associated with high resistance (minimum inhibitory concentration ≥ 32 μg/mL) to LVX. Only a single (Ser479Gly) mutation was found in the gyrB gene in both mucosae. One patient presented isolates with no mutations in the two genes studied. Isolates with the same mutation pattern in individual hosts revealed identical genetic profiles for these genes, confirming that isolates identified in the esophageal mucosa come from isolates colonizing the stomach. Helicobacter pylori resistance to LVX in the esophagus is related to double- and single-point mutations in gyrA and gyrB genes, such as those found in the stomach. Levofloxacin should be applied with caution, because its antibiotic effect on H. pylori is decreasing in Latin America, perhaps owing to high prescription rates.

Author Notes

Address correspondence to Monica Contreras, Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Km. 11 Carretera Panamericana, Altos de Pipe, Edo. Miranda, Venezuela. E-mail: mocontre@ivic.gob.ve or monicacontre@gmail.com

Financial support: This work was supported by Instituto Venezolano de Investigaciones Científicas (IVIC).

Authors’ addresses: Mariela López-Gasca, Jessy Peña, María-Alexandra García-Amado, Fabián Michelangeli, and Monica Contreras, Laboratorio de Fisiología Gastrointestinal, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Miranda, Venezuela, E-mails: mvlopez@ivic.gob.ve, jessykarina.pena@gmail.com, magarcia@ivic.gob.ve, fmichelangeli@gmail.com, and mocontre@ivic.gob.ve.

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