Dominant resistance and negative epistasis can limit the co-selection of de novo resistance mutations and antibiotic resistance genes

Abstract

To tackle the global antibiotic resistance crisis, antibiotic resistance acquired either vertically by chromosomal mutations or horizontally through antibiotic resistance genes (ARGs) have been studied. Yet, little is known about the interactions between the two, which may impact the evolution of antibiotic resistance. Here, we develop a multiplexed barcoded approach to assess the fitness of 144 mutant-ARG combinations in Escherichia coli subjected to eight different antibiotics at 11 different concentrations. While most interactions are neutral, we identify significant interactions for 12% of the mutant-ARG combinations. The ability of most ARGs to confer high-level resistance at a low fitness cost shields the selective dynamics of mutants at low drug concentrations. Therefore, high-fitness mutants are often selected regardless of their resistance level. Finally, we identify strong negative epistasis between two unrelated resistance mechanisms: the tetA tetracycline resistance gene and loss-of-function nuo mutations involved in aminoglycoside tolerance. Our study highlights important constraints that may allow better prediction and control of antibiotic resistance evolution.

Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design

“…However, most of the halogenated compounds entering the environment are persistent with bioaccumulation potential in organisms and adverse effects on human health 4 , 5 . Among them, halogen-containing antibiotics, specially, chloramphenicol (CAP), a suspected carcinogen, was the first synthetic antibiotic to be applied at large scale since 1949 6 , 7 . The excessive use of antibiotics for a long time yields emerging antibiotic-resistant bacteria and antibiotic-resistant genes, becoming a growing public health problem 8 , 9 .…”

Knowledge and Awareness of Physicians About Rational Antibiotic Use and Antimicrobial Resistance Before and After Graduation: A Cross-Sectional Study Conducted in Malatya Province in Turkey

“…This study was carried out between 1 February and 30 April 2019 in Malatya, which has a population of approximately 750 thousand people. This survey study was designed in line with the information obtained from various published research articles, 14,15 and a questionnaire form that we have prepared, including seven sections and twenty-eight questions. Section 1 consisted of demographic data such as age, gender, and professional experience of the individual.…”

Knowledge levels and awareness about rational antibiotic use and antimicrobial resistance before and after graduation: A cross-sectional study conducted in Malatya province, Turkey

“…This study was carried out between 01 February-30 April 2019 in Malatya, which has approximately 750 thousand populations. This study survey was designed in line with the information obtained from various published research articles (9)(10)(11), and the form was prepared, including seven sections and twenty-eight questions. Section 1 consisted of data that included ages, gender, and professional experiences of groups.…”