不孕不育患者解脲脲原体对氟喹诺酮类药物的耐药率及耐药产生机制

袁亚玲; 夏云

doi:10.16016/j.2097-0927.202201142

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不孕不育患者解脲脲原体对氟喹诺酮类药物的耐药率及耐药产生机制

临床医学 | 更新时间：2026-01-09

- 不孕不育患者解脲脲原体对氟喹诺酮类药物的耐药率及耐药产生机制
- Resistance rate and mechanism of ureaplasma urealyticum to fluoroquinolones in infertile patients
- 陆军军医大学学报 2022年44卷第13期页码：1378-1384
- 作者机构：
  
  1.400016 重庆，重庆医科大学附属第一医院检验科
  2.400054 重庆，重庆市第七人民医院检验科
- 作者简介：
  
  [夏云，E-mail：xiayun12cn@aliyun.com XIA Yun, E-mail: xiayun12cn@aliyun.com
- 基金信息：
- DOI：10.16016/j.2097-0927.202201142
  中图分类号： R375.3;R711.6;R915
- 收稿：2022-01-16，
  
  修回：2022-03-03，
  
  纸质出版：2022-07-15
- 稿件说明：
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袁亚玲, 夏云. 不孕不育患者解脲脲原体对氟喹诺酮类药物的耐药率及耐药产生机制[J]. 陆军军医大学学报, 2022,44(13):1378-1384.

Yaling YUAN, Yun XIA. Resistance rate and mechanism of ureaplasma urealyticum to fluoroquinolones in infertile patients[J]. Journal of Army Medical University, 2022, 44(13): 1378-1384.
袁亚玲, 夏云. 不孕不育患者解脲脲原体对氟喹诺酮类药物的耐药率及耐药产生机制[J]. 陆军军医大学学报, 2022,44(13):1378-1384. DOI： 10.16016/j.2097-0927.202201142.

Yaling YUAN, Yun XIA. Resistance rate and mechanism of ureaplasma urealyticum to fluoroquinolones in infertile patients[J]. Journal of Army Medical University, 2022, 44(13): 1378-1384. DOI： 10.16016/j.2097-0927.202201142.

摘要

目的

调查从不孕不育患者分离的解脲脲原体(ureaplasma urealyticum，Uu)对氟喹诺酮类药物的耐药情况，探索拓扑异构酶基因氟喹诺酮耐药决定区(quinolone resistance determining regions

QRDR)突变与耐药性产生的相关性。

方法

收集2019年12月至2022年1月就诊的不孕不育患者泌尿生殖道分离培养的Uu菌株，采用16SrRNA测序进行确认，运用UU295和UUR10_0588两个保守基因将Uu菌株区分为微小脲原体(ureaplasma parvum，UPA)和解脲脲原体(ureaplasma urealyticum，UUR)两个生物群。用微量肉汤稀释法测定环丙沙星、左氧氟沙星、司帕沙星及莫西沙星的最低抑菌浓度。按照CLSI M43-A(2011版)标准筛选耐药菌株，PCR扩增拓扑异构酶基因QRDR，测序结果采用DNASTAR Lasergene分析。用Swiss-Model同源建模服务器对

parC

S83L与

gyrB

R523E突变进行同源建模。

结果

共分离184株临床菌株，UPA 173株(94.0%)，UUR 8株(4.4%)，UPA和UUR共存3株(1.6%)。3组Uu对左氧氟沙星、莫西沙星的耐药率分别为: UPA(80.4%

2.2%)、UUR(50%

0)、UPA和UUR(66.7%，33.3%)。QRDR氨基酸变异(发生率)分别为

parC

S83L(85.3%)、

gyrB

R523E(11.4%)、

parC

L127P(7.1%)、

gyrA

L176F(2.2%)、

gyrA

S174Q(1.6%)、

parE

L408I(1.1%)。其中

parE

L408I为新发现的突变。同源建模发现

parC

S83L突变通过形成空间位阻干扰喹诺酮类药物的正常结合，导致氟喹诺酮类药物耐药。

结论

不孕不育患者人群携带的解脲脲原体对氟喹诺酮类药物的耐药率较高，其耐药与拓扑异构酶基因

parC

S83L碱基突变导致的氨基酸变异密切相关。

Abstract

Objective

To investigate the resistance of ureaplasma urealyticum (Uu) isolated from infertile patients to fluoroquinolones

and explore the correlation between quinolone resistance determining regions (QRDR) mutations in topoisomerase gene and antimicrobial resistance.

Methods

Clinical strains of ureaplasma isolated and cultured from the genitourinary tract of infertile patients who were admitted between December 2019 and January 2022 were collected

and validated by 16SrRNA sequencing. Two conserved genes

UU295 and UUR10_0588

were subsequently adopted to classify the strains into ureaplasma parvum (UPA) and ureaplasma urealyticum (UUR).

In addition

the minimum inhibitory concentrations of ciprofloxacin

levofloxacin

sparfloxacin and moxifloxacin were determined by broth dilution method. The resistant strains were subsequently screened according to CLSI M43-A (2011 edition) standard

topoisomerase gene QRDR was amplified by PCR

and the sequencing results were analyzed using DNASTAR Lasergene. Finally

the homology models of

parC

S83L and

gyrB

R523E mutations were performed by Swiss-model homology modeling server.

Results

A total of 184 clinical strains were isolated

including 173 UPA (94.0%)

8 UUR (4.4%)

and 3 of co-existing (1.6%). The resistance rates of the 3 groups to levofloxacin and moxifloxacin were UPA (80.4%

2.2%)

UUR (50%

and UPA+UUR (66.7%

33.3%)

respectively. The incidence of QRDR amino acid variants was

parC

S83L (85.3%)

gyrB

R523E (11.4%)

parC

L127P (7.1%)

gyrA

L176F (2.2%)

gyrA

S174Q (1.6%)

and

parE

L408I (1.1%)

among which

parE

L408I is a newly discovered mutation. Homology modeling revealed that the

parC

S83L mutation interferes with the normal binding of quinolones by forming spatial hindrance

leading to fluoroquinolone resistance.

Conclusion

The resistance rate of Uu strains to fluoroquinolones in infertile patients is rather high

which is closely related to the amino acid variation caused by the mutation of topoisomerase gene

parC

S83L base.

关键词

Keywords

references

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