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Detection of "Hidden" Antimicrobial Drug Resistance.
ACS Infect Dis 2019; 5(7):1252-1263AI

Abstract

Antimicrobial drug resistance has become a serious public health problem. The current clinical diagnostic methods are turbidity-based assays that have been used for years to track bacterial growth; however, the method is relatively insensitive. To eliminate the new occurrence of drug resistance in infectious bacteria, we developed a highly sensitive EZMTT method for the antibiotic susceptibility test (AST) that magnified the cell growth signal and revealed partial drug resistance (showing 2-20% weak cell growth) that was not detected by the current turbidity assay within 24 h. By simply mixing the EZMTT dye with the bacterial culture and then following the growth by absorbance measurement at 450 nm, the drug-induced proliferation (DIP) rate can be obtained in a high-throughput-screening (HTS) mode with greater than 10-fold better sensitivity than the turbidity assay. The EZMTT-based DIP rate assay of 5 clinically isolated E. coli strains found approximately 30% more partial drug resistance than what was detected in the traditional turbidity-based assay. The observed partial drug resistance was further confirmed by mechanistic analyses. Therefore, a combination of the EZMTT dye and the current clinically used VITEK-type technology has great potential to help understand antimicrobial drug resistance and ultimately provide patients with precise medical care to prevent the occurrence of multidrug resistant bacteria.

Authors+Show Affiliations

Clinical Diagnostic Lab , Renming Hospital of Zhejiang Province , Hangzhou , Zhejiang 310014 , China.College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, IDD & CB , Zhejiang University of Technology , 18 Chaowang Road , Xiachengqu, Hangzhou , Zhejiang 310014 , China.College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, IDD & CB , Zhejiang University of Technology , 18 Chaowang Road , Xiachengqu, Hangzhou , Zhejiang 310014 , China.Center for M. tuberculosis Research , Hangzhou , Zhejiang 310019 , China.College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, IDD & CB , Zhejiang University of Technology , 18 Chaowang Road , Xiachengqu, Hangzhou , Zhejiang 310014 , China.College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, IDD & CB , Zhejiang University of Technology , 18 Chaowang Road , Xiachengqu, Hangzhou , Zhejiang 310014 , China.Department of Surgery , Memorial Sloan Kettering Cancer Center , New York , New York 10009 , United States.School of Life Sciences , University of Warwick , Coventry CV47AJ , United Kingdom.College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, IDD & CB , Zhejiang University of Technology , 18 Chaowang Road , Xiachengqu, Hangzhou , Zhejiang 310014 , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31243989

Citation

Hu, Qingfeng, et al. "Detection of "Hidden" Antimicrobial Drug Resistance." ACS Infectious Diseases, vol. 5, no. 7, 2019, pp. 1252-1263.
Hu Q, Yu Y, Gu D, et al. Detection of "Hidden" Antimicrobial Drug Resistance. ACS Infect Dis. 2019;5(7):1252-1263.
Hu, Q., Yu, Y., Gu, D., Xie, L., Chen, X., Xu, N., ... Ruan, B. H. (2019). Detection of "Hidden" Antimicrobial Drug Resistance. ACS Infectious Diseases, 5(7), pp. 1252-1263. doi:10.1021/acsinfecdis.9b00132.
Hu Q, et al. Detection of "Hidden" Antimicrobial Drug Resistance. ACS Infect Dis. 2019 Jul 12;5(7):1252-1263. PubMed PMID: 31243989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of "Hidden" Antimicrobial Drug Resistance. AU - Hu,Qingfeng, AU - Yu,Yan, AU - Gu,Dongshi, AU - Xie,Li, AU - Chen,Xingrou, AU - Xu,Ning, AU - Ruan,Jennifer Jin, AU - Dowson,Christopher, AU - Ruan,Benfang Helen, Y1 - 2019/06/20/ PY - 2019/6/28/pubmed PY - 2019/6/28/medline PY - 2019/6/28/entrez KW - EZMTT KW - cell growth curve KW - clinical diagnosis KW - drug discovery KW - infectious disease KW - microbial KW - partial drug resistance SP - 1252 EP - 1263 JF - ACS infectious diseases JO - ACS Infect Dis VL - 5 IS - 7 N2 - Antimicrobial drug resistance has become a serious public health problem. The current clinical diagnostic methods are turbidity-based assays that have been used for years to track bacterial growth; however, the method is relatively insensitive. To eliminate the new occurrence of drug resistance in infectious bacteria, we developed a highly sensitive EZMTT method for the antibiotic susceptibility test (AST) that magnified the cell growth signal and revealed partial drug resistance (showing 2-20% weak cell growth) that was not detected by the current turbidity assay within 24 h. By simply mixing the EZMTT dye with the bacterial culture and then following the growth by absorbance measurement at 450 nm, the drug-induced proliferation (DIP) rate can be obtained in a high-throughput-screening (HTS) mode with greater than 10-fold better sensitivity than the turbidity assay. The EZMTT-based DIP rate assay of 5 clinically isolated E. coli strains found approximately 30% more partial drug resistance than what was detected in the traditional turbidity-based assay. The observed partial drug resistance was further confirmed by mechanistic analyses. Therefore, a combination of the EZMTT dye and the current clinically used VITEK-type technology has great potential to help understand antimicrobial drug resistance and ultimately provide patients with precise medical care to prevent the occurrence of multidrug resistant bacteria. SN - 2373-8227 UR - https://www.unboundmedicine.com/medline/citation/31243989/Detection_of_"Hidden"_Antimicrobial_Drug_Resistance L2 - https://dx.doi.org/10.1021/acsinfecdis.9b00132 DB - PRIME DP - Unbound Medicine ER -