Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration

AbstractDetermining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commissionʼs Water Framework Directive’s priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1–2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.

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Deciphering the Impact of Bystander Selection for Antibiotic Resistance in Neisseria gonorrhoeae

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz156 ◽

2019 ◽

Vol 221 (7) ◽

pp. 1033-1035 ◽

Cited By ~ 7

Author(s):

Scott W Olesen ◽

Yonatan H Grad

Keyword(s):

Antibiotic Resistance ◽

Neisseria Gonorrhoeae ◽

Selection For ◽

The Impact

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Chloroxylenol at environmental concentrations can promote conjugative transfer of antibiotic resistance genes by multiple mechanisms

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.151599 ◽

2021 ◽

pp. 151599

Author(s):

Yi Guo ◽

Jingfeng Gao ◽

Yingchao Cui ◽

Zhiqi Wang ◽

Ziqiao Li ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Conjugative Transfer ◽

Environmental Concentrations

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A novel positive selection for identifying cold-sensitive myosin II mutants in Dictyostelium.

Genetics ◽

10.1093/genetics/140.2.505 ◽

1995 ◽

Vol 140 (2) ◽

pp. 505-515 ◽

Cited By ~ 7

Author(s):

B Patterson ◽

J A Spudich

Keyword(s):

Positive Selection ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Time Scale ◽

Myosin Ii ◽

Rapid Onset ◽

Chemical Mutagenesis ◽

Wild Type ◽

Cold Sensitive ◽

Selection For

Abstract We developed a positive selection for myosin heavy chain mutants in Dictyostelium. This selection is based on the fact that brief exposure to azide causes wild-type cells to release from the substrate, whereas myosin null cells remain adherent. This procedure assays myosin function on a time scale of minutes and has therefore allowed us to select rapid-onset cold-sensitive mutants after random chemical mutagenesis of Dictyostelium cells. We developed a rapid technique for determining which mutations lie in sequences of the myosin gene that encode the head (motor) domain and localized 27 of 34 mutants to this domain. We recovered the appropriate sequences from five of the mutants and demonstrated that they retain their cold-sensitive properties when expressed from extrachromosomal plasmids.

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Is formal employment sector hereditary? Determinants of formal/informal sector choice for Mexican male workers

Estudios Económicos de El Colegio de México ◽

10.24201/ee.v34i1.365 ◽

2019 ◽

pp. 91-121

Author(s):

Adelaido García-Andrés ◽

Ernesto Aguayo-Téllez ◽

Jose N. Martínez

Keyword(s):

Positive Selection ◽

Social Mobility ◽

Informal Sector ◽

Formal Sector ◽

Strong Connection ◽

Employment Sector ◽

Formal Employment ◽

Selection For ◽

The Relationship ◽

Employment Choices

Understanding the relationship between parents’ and sons’ formal employment is essential for promoting social mobility in Mexico. Using the 2011 Survey of Social Mobility in Mexico (EMOVI), this paper contributes to the literature by addressing the intergenerational mobility of employment. Findings show a strong connection between intergenerational employment choices and suggest a positive selection for workers. Individuals with parents who worked in the formal sector are more likely to be enrolled in formal work and vice versa. Also, after controlling for parent’s employment sector, schooling remains as a significant vehicle to transit to the formal sector.

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Positive Selection on Two Mitochondrial Coding Genes and Adaptation Signals in Hares (Genus Lepus) from China

10.21203/rs.3.rs-80023/v1 ◽

2020 ◽

Author(s):

Asma Awadi ◽

Hichem Ben Slimen ◽

Helmut Schaschl ◽

Felix Knauer ◽

Franz Suchentrunk

Keyword(s):

Amino Acid ◽

Positive Selection ◽

Protein Function ◽

Transmembrane Domain ◽

Proton Translocation ◽

Introgressive Hybridization ◽

Vibrational Entropy ◽

Mutant Type ◽

Selection For ◽

Protein Variants

Abstract Background: Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. Recent studies of selection on different mitochondrial OXPHOS genes have revealed the adaptive implications of amino acid changes in these subunits. In hares, climatic variation and/or introgression were suggested to be at the origin of such adaptation. Here we looked for evidence of positive selection in three mitochondrial OXPHOS genes, using tests of selection, protein structure modelling and effects of amino acid substitutions on the protein function and stability. We also used statistical models to test for climate and introgression effects on sites under positive selection. Results: Our results revealed seven sites under positive selection in ND4 and three sites in Cytb. However, no sites under positive selection were observed in the COX1 gene. All three subunits presented a high number of codons under negative selection. Sites under positive selection were mapped on the tridimensional structure of the predicted models for the respective mitochondrial subunit. Of the ten amino acid replacements inferred to have evolved under positive selection for both subunits, six were located in the transmembrane domain. On the other hand, three codons were identified as sites lining proton translocation channels. Furthermore, four codons were identified as destabilizing with a significant variation of Δ vibrational entropy energy between wild and mutant type. Moreover, the PROVEAN analysis suggested that among all positively selected sites two fixed amino acid replacements altered the protein functioning. The statistical model runs indicated significant effects of climate on the presence of ND4 and Cytb protein variants, but no effect by trans-specific mitochondrial DNA introgresson.Conclusions: Positive selection was observed in several codons in two OXPHOS genes. We found that substitutions in the positively selected codons have structural and functional impacts on the encoded proteins. Our results are concordantly suggesting that adaptations have strongly affected the evolution of mtDNA of hare species with potential effects on the protein function. Environmental/climatic changes appear to be a major trigger of this adaptation, whereas trans-specific introgressive hybridization seems to play no major role for the occurrence of protein variants.

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Agrichemicals boost the effects of antibiotics on antibiotic resistance evolution

10.7287/peerj.preprints.26925 ◽

2018 ◽

Author(s):

Brigitta Kurenbach ◽

Amy M Hill ◽

William Godsoe ◽

Sophie van Hamelsveld ◽

Jack A Heinemann

Keyword(s):

Antibiotic Resistance ◽

Acquired Resistance ◽

Genotypic Diversity ◽

Microbial Populations ◽

Phenotypic Variance ◽

Short Term ◽

Resistance Evolution ◽

Term Evolution ◽

Comprehensive Test ◽

Selection For

Antibiotic resistance is medicine’s climate change: caused by human activity, and resulting in more extreme outcomes. Resistance emerges in microbial populations when antibiotics act on phenotypic variance within the population. This can arise from either genotypic diversity (resulting from a mutation or horizontal gene transfer), or from ‘adaptive’ differences in gene expression due to environmental variation. Adaptive changes can increase fitness allowing bacteria to survive at higher concentrations of the antibiotic. They can also decrease fitness, potentially leading to selection for antibiotic resistance at lower concentrations. There are opportunities for other environmental stressors to promote antibiotic resistance in ways that are hard to predict using conventional assays. Exploiting our observation that commonly used herbicides can increase or decrease the minimum inhibitory concentration (MIC) of different antibiotics, we provide the first comprehensive test of the hypothesis that the rate of antibiotic resistance evolution under specified conditions can increase, regardless of whether a herbicide increases or decreases the antibiotic MIC. Short term evolution experiments were used for various herbicide and antibiotic combinations. We found conditions where acquired resistance arises more frequently regardless of whether the exogenous non-antibiotic agent increased or decreased antibiotic effectiveness. This “damned if you do/damned if you don’t” outcome suggests that the emergence of antibiotic resistance is exacerbated by additional environmental factors that influence competition between bacteria. Our work demonstrates that bacteria may acquire antibiotic resistance in the environment at rates substantially faster than predicted from laboratory conditions.

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[1] New bacteriophage lambda vectors with positive selection for cloned insects

Recombinant DNA Part C - Methods in Enzymology ◽

10.1016/0076-6879(83)01004-6 ◽

1983 ◽

pp. 3-19 ◽

Cited By ~ 25

Author(s):

Jonathan Karn ◽

Sydney Brenner ◽

Leslie Barnett

Keyword(s):

Positive Selection ◽

Bacteriophage Lambda ◽

Selection For

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Understanding the basis of antibiotic resistance: a platform for drug discovery

Microbiology ◽

10.1099/mic.0.082412-0 ◽

2014 ◽

Vol 160 (11) ◽

pp. 2366-2373 ◽

Cited By ~ 28

Author(s):

Laura J. V. Piddock

Keyword(s):

Antibiotic Resistance ◽

Salmonella Enterica ◽

Efflux Pump ◽

Antibiotic Resistance Genes ◽

Multi Drug Resistance ◽

Annual Conference ◽

Altered Expression ◽

Genetic Inactivation ◽

Fluoroquinolone Antibiotics ◽

Serovar Typhimurium

There are numerous genes in Salmonella enterica serovar Typhimurium that can confer resistance to fluoroquinolone antibiotics, including those that encode topoisomerase proteins, the primary targets of this class of drugs. However, resistance is often multifactorial in clinical isolates and it is not uncommon to also detect mutations in genes that affect the expression of proteins involved in permeability and multi-drug efflux. The latter mechanism, mediated by tripartite efflux systems, such as that formed by the AcrAB–TolC system, confers inherent resistance to many antibiotics, detergents and biocides. Genetic inactivation of efflux genes gives multi-drug hyper-susceptibility, and in the absence of an intact AcrAB–TolC system some chromosomal and transmissible antibiotic resistance genes no longer confer clinically relevant levels of resistance. Furthermore, a functional multi-drug resistance efflux pump, such as AcrAB–TolC, is required for virulence and the ability to form a biofilm. In part, this is due to altered expression of virulence and biofilm genes being sensitive to efflux status. Efflux pump expression can be increased, usually due to mutations in regulatory genes, and this confers resistance to clinically useful drugs such as fluoroquinolones and β-lactams. Here, I discuss some of the work my team has carried out characterizing the mechanisms of antibiotic resistance in Salmonella enterica serovar Typhimurium from the late 1980s to 2014. A video of this Prize Lecture, presented at the Society for General Microbiology Annual Conference 2014, can be viewed via this link: https://www.youtube.com/watch?v=MCRumMV99Yw.

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