Fitness Tradeoffs of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli

Basra, Prabh; Alsaadi, Ahlam; Bernal-Astrain, Gabriela; O’Sullivan, Michael Liam; Hazlett, Bryn; Clarke, Leah; Schoenrock, Andrew; Pitre, Sylvain; Wong, Alex

doi:10.1093/gbe/evy030

Cited by 63 publications

(67 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many resistance‐conferring mutations appear to have little or no fitness cost (Sander et al., ), and compensatory mutations may obliterate any costs or indeed confer a fitness advantage (Schrag, Perrot, & Levin, ) in some environments (Basra et al., ). Some resistances are at least partly mediated by constitutive efflux mechanisms, for which the machinery of the cell is already well‐adapted (Maillard et al., ).…”

Section: Control and Elimination Of Amr Organismsmentioning

confidence: 99%

Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection

Davies

Wales

2019

Comp Rev Food Sci Food Safe

120

View full text Add to dashboard Cite

Resistance to therapeutic antimicrobial agents is recognized as a growing problem for both human and veterinary medicine, and the need to address the issue in both of these linked domains is a current priority in public policy. Efforts to limit antimicrobial resistance (AMR) on farms have so far focused on control of the supply and use of antimicrobial drugs, plus husbandry measures to reduce infectious disease. In the United Kingdom and some other countries, substantial progress has been made recently against targets on agricultural antimicrobial drug use. However, evidence suggests that resistant pathogenic and commensal bacteria can persist and spread within and between premises despite declining or zero antimicrobial drug use. Reasons for this are likely complex and varied but may include: bacterial adaptations to ameliorate fitness costs associated with maintenance and replication of resistance genes and associated proteins, horizontal transmission of genetic resistance determinants between bacteria, physical transfer of bacteria via movement (of animals, workers, and equipment), ineffective cleaning and disinfection, and co‐selection of resistance to certain drugs by use of other antimicrobials, heavy metals, or biocides. Areas of particular concern for public health include extended‐spectrum cephalosporinases and fluoroquinolone resistance among Enterobacteriaceae, livestock‐associated methicillin‐resistant Staphylococcus aureus, and the emergence of transmissible colistin resistance. Aspects of biosecurity have repeatedly been identified as risk factors for the presence of AMR on farm premises, but there are large gaps in our understanding of the most important risk factors and the most effective interventions. The present review aims to summarize the present state of knowledge in this area, from a European perspective.

show abstract

Section: Control and Elimination Of Amr Organismsmentioning

confidence: 99%

Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection

Davies

Wales

2019

Comp Rev Food Sci Food Safe

120

View full text Add to dashboard Cite

show abstract

“…We propose two explanations. First, the resistance to fluoroquinolones displayed by clade C may come at a direct cost (43). This cost would not be revealed in maximum growth rate in planktonic conditions, but would manifest as a lower colonization ability.…”

Section: Discussionmentioning

confidence: 99%

Success of Escherichia coli O25b:H4 ST131 clade C associated with a decrease in virulence

Duprilot

Baron

Blanquart

et al. 2019

Preprint

View full text Add to dashboard Cite

word count: 248 22 Text word count: 5256 23 24 25 2 Abstract 26 Escherichia coli of sequence type (ST) 131 resistant to fluoroquinolones and producer of 27CTX-M-15 is globally one of the major extraintestinal pathogenic E. coli (ExPEC). ST131 28 phylogenesis showed that multidrug-resistant ST131 strains belong to a clade called C, 29 descending from an ancestral clade called B, comprising mostly antibiotic-susceptible strains. 30 Antibiotic resistance could appear as one of the keys of the clade C global success. We 31 hypothesized that other features of ST131 clade C could contribute to this success since other 32 major global ExPEC clones (ST73, ST95) are mostly antibiotic-susceptible. To test this 33 hypothesis, we measured the growth abilities, early biofilm formation and virulence-factor 34 content of a collection of clade B and clade C strains. Moreover, using competition assays, we 35 measured the capacity of selected representative strains of clades B and C to colonize the 36 mouse intestine and urinary tract, and to kill mice in a septicemia model. Clade B and C 37 strains had similar growth ability. However, clade B strains were more frequently early 38 biofilm producers, expressed mostly faster their type 1 fimbriae and displayed more virulence 39 factor-encoding genes than clade C strains. Clade B outcompeted clade C in the gut and/or 40 urinary tract colonization models and in the septicemia model. These results strongly suggest 41 that clade C strain evolution includes a loss of virulence, i.e. a process that could enhance 42 micro-organism persistence in a given host and thus optimize transmission. This process, 43 associated with acquired antibiotic-resistance, could ensure clade C strain survival in 44 environments under antibiotic pressure.45 46 47 48 49 50 3 Importance 51Extraintestinal pathogen Escherichia coli (ExPEC) are virulent but mostly antibiotic-52 susceptible. One worrying exception is ST131, a major multidrug resistant ExPEC clone that 53 has spread worldwide since the 2000s. To contain the emergence of this threatening clone, we 54 need to understand what factors favored its emergence and dissemination. Here, we 55 investigated whether multidrug-resistant ST131 had advantageous phenotypic properties 56 beyond multidrug resistance. To this end, we competed the emergent multidrug-resistant 57 ST131 with its antibiotic-susceptible ancestor in different conditions: biofilm production, in 58 vivo colonization and virulence experiments. In all in vivo competitions, we found that 59 multidrug-resistant ST131 was losing to its ancestor, suggesting a lesser virulence of 60 multidrug-resistant ST131. It was previously described that losing virulence can increase 61 micro-organism persistence in some populations and subsequently its level of transmissibility. 62Thus, a decreased level of virulence, associated with multidrug resistance, could explain the 63 global success of ST131. 64 65 66 67 68 69 70 71 72 73 74 75 In the last two decades, Escherichia coli O25b:H4 of sequence type (ST) ...

show abstract

“…The most common way for bacteria to become resistant to fluoroquinolones is through mutations in DNA Gyrase and Topoisomerase IV. In E. coli, S83L and D87N mutations in GyrA are common in fluoroquinolone resistant clinical isolates, with the S83L/D87N double mutant conferring particularly high levels of resistance (Basra et al 2018). These mutations affect the target sites of fluoroquinolones and cause the antibiotic to lose its ability to form enzyme-DNA-drug complexes, resulting in resistance.…”

Section: Mechanisms Of Resistancementioning

confidence: 99%

Investigating the Effects of Genetic Background on the Fitness of Quinolone Resistance Mutations in Escherichia Coli

Hazlett¹

Self Cite

View full text Add to dashboard Cite

Antimicrobial resistance (AMR) is one of the largest threats to public health and puts a serious strain on healthcare systems around the world. Many first line antibiotics can no longer be used to fight infections due to increased resistance. The fitness of AMR strains of bacteria is determined in part by epistasis, whereby resistance mutations may have different effects on different genetic backgrounds. Thus, the objective of this research is to investigate the effects of genotype on the fitness of AMR. Using genetic techniques in E. coli, quinolone resistance alleles of the gyrA gene (S83L, D87N, and a combination of S83L-D87N) were transferred into a collection of knockout strains, resulting in approximately 12 000 double-mutants. Genetic interactions that affected fitness, both positively and negatively, were common and a variety of synthetic lethal/sick interactions were found. A number of the genes lethal with gyrA mutations were involved in DNA synthesis, repair, and replication, much like gyrA itself. Using strains that were able to conditionally express the knocked out genes, yield and growth curves were examined over a 24 hour period to validate the synthetic lethal interactions.Results varied for each strain -of 33 strains assayed, 21 showed a deficit in at least one fitness-related phenotype. Overall, more work should be done to further examine these putative synthetic lethal interactions. Once done, looking at all these genetic interactions will help to untangle the functionality of certain genes and, in the context of AMR, identification of synthetic lethal interactions of AMR mutations may lead to drug targets that can specifically kill resistant bacteria.iii

show abstract

Fitness Tradeoffs of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli

Cited by 63 publications

References 85 publications

Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection

Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection

Success of Escherichia coli O25b:H4 ST131 clade C associated with a decrease in virulence

Investigating the Effects of Genetic Background on the Fitness of Quinolone Resistance Mutations in Escherichia Coli

Contact Info

Product

Resources

About