Abstract

The fitness cost of antibiotic resistance is a crucial factor to determine the evolutionary and transmission success of resistant bacteria. Exploring the fitness cost and compensation mechanism of antibiotic resistance genes (ARGs) in bacteria may effectively reduce the transmission of drug-resistant genes in the environment. Engineered bacteria with the same genetic background that carry sulfonamide resistance gene were generated to explore the fitness cost of sulfonamide resistance gene in Escherichia coli. There were significant differences in the protein expression of the two-component system pathway (fliZ, fliA, fliC and lrhA), folate biosynthesis pathway (sul1, sul2 and sul3), ABC transporter system (ugpC, rbsA and gsiA), and outer membrane pore protein OmpD through the comparative analysis of differential proteins compared to sensitive bacteria. Thus, we could speculate the possible fitness compensation mechanism. Finally, quantitative Real-time PCR (qRT-PCR) was used to verify the functions of some differential proteins at the transcriptional level. The fitness cost and compensatory evolution of antibiotic resistance are an essential part of bacterial evolution.

Highlights

  • IntroductionThe spread of MDR (multidrug-resistant) amongst Gram-negative bacteria has emerged as one of the most pressing global public health threats [1]

  • The spread of MDR amongst Gram-negative bacteria has emerged as one of the most pressing global public health threats [1]

  • The compensation mechanism of sulfonamide resistance genes in E. coli was explored in constructed engineered bacteria carrying sul1, sul2 and sul3 genes

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Summary

Introduction

The spread of MDR (multidrug-resistant) amongst Gram-negative bacteria has emerged as one of the most pressing global public health threats [1]. While sulfonamides play a substantial role in preventing and treating animal bacterial diseases, bacteria have developed extensive and robust resistance to them [3]. Bacteria usually produce resistance to sulfonamides through two different strategies: (i) gene mutation and (ii) gene substitution. The gene folP of dihydrosphenoic acid synthase (DHPS), located on the chromosome, produces drug resistance [4]. Drug resistance is generated by obtaining DHPS replacement genes sul, sul and sul. The fitness cost of antibiotic resistance is a crucial factor to determine the evolutionary success of resistant bacteria. Even if the selection pressure in the environment is eliminated, drug-resistant bacteria can still compensate for drugresistant genes' fitness cost through some compensation mechanisms. The fitness cost and compensatory evolution of antibiotic resistance are an essential part of bacterial evolution

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