Subscriber access provided by AUSTRALIAN NATIONAL UNIV
Article 2
TiO Assisted Laser Desorption/Ionization Mass Spectrometry for Rapid Profiling of Candidate Metabolite Biomarkers from Antimicrobial Resistant Bacteria Rutan Zhang, Qin Qin, Baohong Liu, and Liang Qiao Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b04565 • Publication Date (Web): 20 Feb 2018 Downloaded from http://pubs.acs.org on February 23, 2018
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Analytical Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Analytical Chemistry
TiO2 Assisted Laser Desorption/Ionization Mass Spectrometry for Rapid Profiling of Candidate Metabolite Biomarkers from Antimicrobial Resistant Bacteria Rutan Zhang,† Qin Qin,‡ Baohong Liu† and Liang Qiao*,† †
Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
‡
Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
ABSTRACT: Antimicrobial resistance (AMR) is one of the most serious problems affecting public health and safety. It is crucial to understand antimicrobial resistance from molecular level. In this work, TiO2 assisted laser desorption/ionization (LDI) mass spectrometry (MS) was used for fast metabolites analysis from intact bacterial cells to discriminate different strains of bacteria and to detect AMR. With the mass spectra of bacterial metabolites by TiO2-LDI MS, multivariable analysis was performed for bacterial identification to find out distinctive metabolites as potential biomarkers. The most statistically significant metabolites were screened out by the method and further identified using liquid-chromatography (LC) tandem MS (MS/MS). Robustness of our developed methods in bacterial taxonomy was demonstrated by iterative validation using 48 clinical samples. The strategy was further illustrated with 3 clinical strains of ESBL (Extended-Spectrum betaLactamases-resistant) positive E. coli and 4 clinical strains of ESBL negative ones. 11 key metabolites were identified as potential biomarkers of ESBL positive E. coli. We also implemented pathway and network analysis on the key metabolites to prove the feasibility of our method in executing metabolomics analysis. Comparing to the most prevalent techniques in metabolomics study, such as LC-MS, gas chromatographyMS and nuclear magnetic resonance spectroscopy, the current method gains in simple sample preparation and short analysis time, thereby fits especially in clinical usages and fast analyses.
Microorganisms play a critical role in sustaining lives as they account for nearly one third of the Earth’s biomass.1 There are more than 1,000 species of bacteria in human gut.2 Some bacteria benefit health, while the others severely damage normal physiology. Recent threats to public safety posed by bioterrorism, microbial contamination of food3 and clinical bacterial infection have underlined the need for fast and robust methods of microbial detection. For decades, emergence of drug-resistant bacteria due to bacterial genovariation and overuse of antibiotics has been a serious problem threatening human health, which can increase the risk of bacterial infection and mortality rate. According to the Review on Antimicrobial Resistance (AMR), worldwide deaths attributable to antimicrobial resistant bacteria could reach 10 million by 2050.4 Recent research has revealed that resistant strains have some defects in central pathways of metabolites. Peng and co-authors observed that kanamycin-resistant Edwardsiella tarda could restore drug sensitivity through exogenous addition of alanine and/or glucose.5 Thereby, it is important to examine how the states of metabolites vary in drug-resistant bacteria. Metabolites, which are non-genetically encoded small molecules with molecular weight
