Climate change exacerbates pest damage through reduced pesticide efficacy.

Pesticide efficacy is strongly associated with environmental conditions. Conditional resistance defined as a reduction in pesticide sensitivity under changed environmental conditions has been widely detected under climatic changes such as elevated temperatures and CO2 enrichment. Given the effects of environmental conditions on pesticide sensitivity, many of the putative resistance reports made by farmers may be due to pesticide application followed by non-optimal environmental conditions rather than the evolution of resistance. This type of conditional resistance may be the result of phenotypic plasticity or epigenetic changes in response to environmental changes. Elevated temperatures and CO2 enrichment can directly lead to reduced pesticide efficacy by altering pesticide metabolism and translocation, or indirectly increasing pesticide detoxification in host-plants thus reducing pesticide availability for the target pest. Stress-related signal transduction pathways, as well as physiological changes, can both be associated with accelerated pesticide detoxification under climatic changes. The possibility for parallel mechanisms controlling these responses in different pest species should be considered. It is proposed that the same mechanisms leading to non-target site resistance in pests may also play a role in conditional resistance, suggesting we can predict the pesticides to which pests are likely to be less responsive under changing climatic conditions. Using adjuvants to improve pesticide translocation or reduce pesticide metabolism, alongside with new technologies such as using nanoparticles may result in higher pesticide functionality under the projected climate change. Exploring the physiological, transcriptional and biochemical basis underlying conditional resistance is crucial in maintaining future pest management under changing environmental conditions. © 2018 Society of Chemical Industry.

Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine.

Mecillinam (amdinocillin) is a ß-lactam antibiotic used to treat uncomplicated urinary tract infections (UTIs). We have previously shown that inactivation of the Escherichia coli cysB gene is the major cause of mecillinam resistance (MecR) in clinical isolates. In this study, we used different E. coli strains (laboratory and clinical isolates) that were MecR due to cysB mutations to determine how mecillinam susceptibility was affected during growth in urine compared to growth in the commonly used growth medium Mueller Hinton (MHB). We also examined mecillinam susceptibility when bacteria were grown in urine obtained from 48 different healthy volunteers. Metabolome analysis was done on the urine samples and the association between the mecillinam susceptibility patterns of the bacteria and urine metabolite levels was studied. Two major findings with clinical significance are reported. First, MecRE. coli cysB mutant strains (both laboratory and clinical isolates) were always more susceptible to mecillinam when grown in urine as compared to laboratory medium, with many strains showing complete phenotypic susceptibility in urine. Second, the degree of reversion to susceptibility varied between urine samples obtained from different individuals. This difference was correlated with osmolality such that in urine with low osmolality the MecR mutants were more susceptible to mecillinam than in urine with high osmolality. This is the first example describing conditional resistance where a genetically stable antibiotic resistance can be phenotypically reverted to susceptibility by metabolites present in urine. These findings have several important clinical implications regarding the use of mecillinam to treat UTIs. First, they suggest that mecillinam can be used to treat also those clinical strains that are identified as MecR in standard laboratory tests. Second, the results suggest that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant susceptibility testing results. Third, these findings imply that changes in patient behavior, such as increased water intake or use of diuretics to reduce urine osmolality and increased intake of cysteine, might induce antibiotic susceptibility in an infecting MecRE. coli strain and thereby increase treatment efficiency.