Extended spectrum β-lactamase-producing Escherichia coli forms filaments as an initial response to cefotaxime treatment

Extended spectrum β-lactamase-producing Escherichia coli forms filaments as an initial response to cefotaxime treatment
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DOI:
10.1186/s12866-015-0399-3
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发表时间:
2015-03-08
期刊:
影响因子:
4.2
通讯作者:
Olsen, John E.
Olsen, John E.
中科院分区:
生物学3区
文献类型:
--
作者:
Kjeldsen, Thea S. B.;Sommer, Morten O. A.;Olsen, John E.

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背景资料:β-内酰胺靶向细菌细胞壁中的肽聚糖层,并且大多数β-内酰胺抗生素在低浓度下引起敏感的革兰氏阴性菌的抑制。目的是确定头孢菌素耐药产CTX-M-1大肠杆菌的初始形态学反应。结果:2株染色体携带bla(CTX-M-1)和IncI 1质粒携带bla(CTX-M-1)的耐药菌株和3株敏感菌株对头孢噻肟的敏感性分别为100%和100%。当暴露于亚抑制浓度以及治疗浓度(1至512 mg/L的头孢噻肟)的头孢噻肟时,在滞后期和早期指数期,耐药菌株显示出伸长的细胞,这表明伸长是对抗生素的初始反应机制。正常大小的细胞是指数生长期和静止生长期的优势细胞类型。在没有头孢噻肟的培养物中没有观察到伸长的细胞。在高浓度头孢噻肟(128-512 mg/L)的培养物中,除了初始的抑制外,没有观察到生长,但在耐药菌株的培养物中,14-17小时后出现球形平板。在敏感的对照菌株中也观察到丝状体的存在。对β-内酰胺类抗生素产生耐药性的大肠杆菌,当暴露于头孢噻肟时,产生丝状体。丝状体的形成仅限于早期生长阶段,细胞生长为丝状体的时间依赖于抗生素浓度。这表明耐抗生素E.大肠杆菌在β-内酰胺抗生素存在下经历与敏感细菌相同的形态学变化。结果表明,丝的形成是对抗生素的初始反应。
Background: beta-lactams target the peptidoglycan layer in the bacterial cell wall and most beta-lactam antibiotics cause filamentation in susceptible Gram-negative bacteria at low concentrations. The objective was to determine the initial morphological response of cephalosporin resistant CTX-M-1-producing E. coli to cefotaxime and to determine whether the response depended on the growth phase of the bacterium and the concentration of antibiotic.Results: Two antibiotic resistant strains carrying bla(CTX-M-1) on the chromosome and on an IncI1 plasmid and three sensitive strains were used in this study. The resistant strains displayed elongated cells when exposed to cefotaxime at sub-inhibitory as well as therapeutic concentrations (1 to 512 mg/L of cefotaxime) in both lag and early exponential phase, suggesting that the elongation was an initial response mechanism to the antibiotic. Normal sized cells were the dominant cell type in exponential and stationary growth phase. No elongated cells were seen in cultures without cefotaxime. In cultures with high concentrations of cefotaxime (128-512 mg/L), no growth other than initial filamentation was observed, but spheroplats appeared after 14-17 hours in cultures of the resistant strains. Filaments were also observed in sensitive control strains with sub-inhibitory concentrations of cefotaxime.Conclusions: We showed that E. coli resistant to beta-lactams by an extended-spectrum beta-lactamase, bla(CTX-M-1), produced filaments when exposed to cefotaxime. The filament formation was restricted to early growth phases and the time the cells grew as filaments was antibiotic concentration dependent. This indicates that antibiotic resistant E. coli undergo the same morphological changes as sensitive bacteria in the presence of beta-lactam antibiotic. It was showed that the filament formation was an initial response to the antibiotics.