Enhancing the Efficacy of Chloramphenicol Therapy for Escherichia coli by Targeting the Secondary Resistome

被引:5
作者
Alobaidallah, Mosaed Saleh A. [1 ,2 ,3 ]
Garcia, Vanesa [1 ,4 ]
Wellner, Sandra M. [1 ]
Thomsen, Line E. [1 ]
Herrero-Fresno, Ana [1 ,5 ]
Olsen, John Elmerdahl [1 ]
机构
[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet & Anim Sci, DK-1870 Frederiksberg, Denmark
[2] King Saud Bin Abdulaziz Univ Hlth Sci, Coll Appl Med Sci, Dept Clin Lab Sci, Jeddah 21423, Saudi Arabia
[3] King Abdullah Int Med Res Ctr, Jeddah 22384, Saudi Arabia
[4] Univ Santiago De Compostela USC, Fac Vet, Dept Microbiol & Parasitoloxia, Lab Referencia Escherichia Coli LREC, Lugo 27002, Spain
[5] Univ Santiago De Compostela USC, Fac Sci, Dept Biochem & Mol Biol, Campus Terra, Lugo 27002, Spain
来源
ANTIBIOTICS-BASEL | 2024年 / 13卷 / 01期
关键词
Escherichia coli; chloramphenicol; multi-drug-resistant bacteria; extended-spectrum beta-lactamase; transposon-directed insertion site sequencing; antibiotic adjuvants; MEMBRANE VESICLE PRODUCTION; CHROMOSOMAL GENES; MULTIDRUG-RESISTANCE; EFFLUX PUMP; PROTEIN; INACTIVATION; ANTIBIOTICS; INFECTIONS; EXPRESSION; ACRB;
D O I
10.3390/antibiotics13010073
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The increasing prevalence of antimicrobial resistance and the limited availability of new antimicrobial agents have created an urgent need for new approaches to combat these issues. One such approach involves reevaluating the use of old antibiotics to ensure their appropriate usage and maximize their effectiveness, as older antibiotics could help alleviate the burden on newer agents. An example of such an antibiotic is chloramphenicol (CHL), which is rarely used due to its hematological toxicity. In the current study, we employed a previously published transposon mutant library in MG1655/pTF2::bla(CTX-M-1), containing over 315,000 unique transposon insertions, to identify the genetic factors that play an important role during growth in the presence of CHL. The list of conditionally essential genes, collectively referred to as the secondary resistome (SR), included 67 genes. To validate our findings, we conducted gene knockout experiments on six genes: arcA, hfq, acrZ, cls, mdfA, and nlpI. Deleting these genes resulted in increased susceptibility to CHL as demonstrated by MIC estimations and growth experiments, suggesting that targeting the products encoded from these genes may reduce the dose of CHL needed for treatment and hence reduce the toxicity associated with CHL treatment. Thus, the gene products are indicated as targets for antibiotic adjuvants to favor the use of CHL in modern medicine.
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页数:14
相关论文
共 64 条
[1]  
Almeida S., 2022, Lus. Sci. J, P3, DOI [10.48687/lsj.95, DOI 10.48687/LSJ.95]
[2]   Uncovering the Important Genetic Factors for Growth during Cefotaxime-Gentamicin Combination Treatment in blaCTX-M-1 Encoding Escherichia coli [J].
Alobaidallah, Mosaed Saleh A. ;
Garcia, Vanesa ;
De Mets, Richard ;
Wellner, Sandra M. ;
Thomsen, Line E. ;
Herrero-Fresno, Ana ;
Olsen, John Elmerdahl .
ANTIBIOTICS-BASEL, 2023, 12 (06)
[3]   The TraDIS toolkit: sequencing and analysis for dense transposon mutant libraries [J].
Barquist, Lars ;
Mayho, Matthew ;
Cummins, Carla ;
Cain, Amy K. ;
Boinett, Christine J. ;
Page, Andrew J. ;
Langridge, Gemma C. ;
Quail, Michael A. ;
Keane, Jacqueline A. ;
Parkhill, Julian .
BIOINFORMATICS, 2016, 32 (07) :1109-1111
[4]   CHLORAMPHENICOL-ASSOCIATED BLOOD DYSCRASIAS - A REVIEW OF CASES SUBMITTED TO AMERICAN MEDICAL ASSOCIATION REGISTRY [J].
BEST, WR .
JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1967, 201 (03) :181-&
[5]   The Calgary Biofilm Device: New technology for rapid determination of antibiotic susceptibilities of bacterial biofilms [J].
Ceri, H ;
Olson, ME ;
Stremick, C ;
Read, RR ;
Morck, D ;
Buret, A .
JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (06) :1771-1776
[6]  
Clinical and Laboratory Standards Institute, 2015, M100S25 CLSI
[7]   One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products [J].
Datsenko, KA ;
Wanner, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6640-6645
[8]   Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps [J].
De Gaetano, Giuseppe Valerio ;
Lentini, Germana ;
Fama, Agata ;
Coppolino, Francesco ;
Beninati, Concetta .
ANTIBIOTICS-BASEL, 2023, 12 (06)
[9]   Antibiotic marker modifications of λ Red and FLP helper plasmids, pKD46 and pCP20, for inactivation of chromosomal genes using PCR products in multidrug-resistant strains [J].
Doublet, Benoit ;
Douard, Gregory ;
Targant, Hayette ;
Meunier, Daniele ;
Madec, Jean-Yves ;
Cloeckaert, Axel .
JOURNAL OF MICROBIOLOGICAL METHODS, 2008, 75 (02) :359-361
[10]   Unraveling the Physiological Complexities of Antibiotic Lethality [J].
Dwyer, Daniel J. ;
Collins, James J. ;
Walker, Graham C. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55, 2015, 55 :313-332