Analysis of clinical isolates of Helicobacter pylori in Pakistan reveals high degrees of pathogenicity and high frequencies of antibiotic resistance.
Analysis of clinical isolates of Helicobacter pylori in Pakistan reveals high degrees of pathogenicity and high frequencies of antibiotic resistance.
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DOI：
10.1111/hel.12142
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发表时间：
2014-10
期刊：
影响因子：
4.4
通讯作者：
Pritchard DM
中科院分区：
文献类型：
--
作者：
Rasheed F;Campbell BJ;Alfizah H;Varro A;Zahra R;Yamaoka Y;Pritchard DM
幽门螺杆菌的抗生素耐药性导致根除感染失败，最常见的原因是一些关键基因的点突变和错义突变。通过 Etest 测定了 46 名巴基斯坦患者的幽门螺杆菌分离株的抗生素敏感性。扩增抗性和致病性基因，并分析序列以确定突变的存在。大部分分离株 (73.9%) 对甲硝唑 (MTZ) 耐药，对克拉霉素 (CLR；47.8%) 和阿莫西林 (AML；54.3%) 也有相当大的耐药性。相对较少的分离株对四环素（TET；4.3%）或环丙沙星（CIP；13%）具有耐药性。然而，大多数分离株 (n = 43) 对一种或多种抗生素表现出耐药性。 MTZ 抗性分离株在不依赖于氧的 NADPH 硝基还原酶（RdxA；发现 8 个突变）和 NADH 黄素氧化还原酶（FrxA；发现 4 个突变）中含有错义突变。在负责 CLR 抗性的 23S rRNA 基因中，发现了一个新的点突变 (A2181G) 和 4 个先前报道的突变。致病基因 cagA、dupA 和 vacA s1a/m1 在分离株中频繁检测到，这些分离株也对 MTZ、CLR 和 AML 具有抗性。在这些患者中还观察到较高比例的 CagA 和 VacA 血清阳性。部分序列的系统发育分析显示 cagA 的 3' 区域在整个树中均匀分布。我们在巴基斯坦发现了幽门螺杆菌分离株，它们含有致病基因，并且由于获得了多个点突变和错义突变而具有令人担忧的抗生素耐药性。因此，在这种情况下应重新评估幽门螺杆菌根除方案。
Antibiotic resistance in Helicobacter pylori contributes to failure in eradicating the infection and is most often due to point and missense mutations in a few key genes. The antibiotic susceptibility profiles of H. pylori isolates from 46 Pakistani patients were determined by Etest. Resistance and pathogenicity genes were amplified, and sequences were analyzed to determine the presence of mutations. A high percentage of isolates (73.9%) were resistant to metronidazole (MTZ), with considerable resistance to clarithromycin (CLR; 47.8%) and amoxicillin (AML; 54.3%) also observed. Relatively few isolates were resistant to tetracycline (TET; 4.3%) or to ciprofloxacin (CIP; 13%). However, most isolates (n = 43) exhibited resistance to one or more antibiotics. MTZ-resistant isolates contained missense mutations in oxygen-independent NADPH nitroreductase (RdxA; 8 mutations found) and NADH flavin oxidoreductase (FrxA; 4 mutations found). In the 23S rRNA gene, responsible for CLR resistance, a new point mutation (A2181G) and 4 previously reported mutations were identified. Pathogenicity genes cagA, dupA, and vacA s1a/m1 were detected frequently in isolates which were also found to be resistant to MTZ, CLR, and AML. A high percentage of CagA and VacA seropositivity was also observed in these patients. Phylogenetic analysis of partial sequences showed uniform distribution of the 3′ region of cagA throughout the tree. We have identified H. pylori isolates in Pakistan which harbor pathogenicity genes and worrying antibiotic resistance profiles as a result of having acquired multiple point and missense mutations. H. pylori eradication regimens should therefore be reevaluated in this setting.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Engstrand, L