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Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions.

ABSTRACT: Mutations conferring resistance to one antibiotic can increase (cross-resistance) or decrease (collateral sensitivity) resistance to others. Antibiotic combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requires understanding whether collateral effects are robust across different environmental conditions. Here, we isolated and characterized resistant mutants of Escherichia coli using five antibiotics, before measuring collateral effects on resistance to other paired antibiotics. During both isolation and phenotyping, we varied conditions in ways relevant in nature (pH, temperature, and bile). This revealed that local abiotic conditions modified expression of resistance against both the antibiotic used during isolation and other antibiotics. Consequently, local conditions influenced collateral sensitivity in two ways: by favoring different sets of mutants (with different collateral sensitivities) and by modifying expression of collateral effects for individual mutants. These results place collateral sensitivity in the context of environmental variation, with important implications for translation to real-world applications. IMPORTANCE When bacteria become resistant to an antibiotic, the genetic changes involved sometimes increase (cross-resistance) or decrease (collateral sensitivity) their resistance to other antibiotics. Antibiotic combinations showing repeatable collateral sensitivity could be used in treatment to slow resistance evolution. However, collateral sensitivity interactions may depend on the local environmental conditions that bacteria experience, potentially reducing repeatability and clinical application. Here, we show that variation in local conditions (pH, temperature, and bile salts) can influence collateral sensitivity in two ways: by favoring different sets of mutants during bacterial resistance evolution (with different collateral sensitivities to other antibiotics) and by modifying expression of collateral effects for individual mutants. This suggests that translation from the lab to the clinic of new approaches exploiting collateral sensitivity will be influenced by local abiotic conditions.

SUBMITTER: Allen RC

PROVIDER: S-EPMC8631318 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The abundance of arthropods is declining globally, and human-modification of natural habitat is a primary driver of these declines. Arthropod declines are concerning because arthropods mediate critical ecosystem functions, and sustained declines may lead to cascading trophic effects. There is growing evidence that properly managed urban environments can provide refugium to arthropods, but few cities have examined arthropods within urban greenspaces to evaluate their management efforts. In this study, we surveyed arthropod communities within a medium-sized, growing city. We investigated arthropod communities (abundance, richness, diversity, community composition) within 16 urban greenspaces across metropolitan Grand Rapids, Michigan (USA). We focused our efforts on urban gardens and pocket prairies, and measured environmental variables at each site. We collected 5,468 individual arthropods that spanned 14 taxonomic orders and 66 morphospecies. The results showed that community composition was influenced by impervious surface, white flower abundance, and humidity. Total arthropod abundance and diversity were positively associated with humidity. For specific orders, Hymenoptera (bees, ants, wasps) abundance was negatively associated with temperature, and positively associated with site perimeter-area ratio. Hemiptera (true bugs) were negatively associated with impervious surface and positively associated with humidity. These findings show that impervious surfaces impact arthropod communities, but many of the observed changes were driven by local abiotic conditions like temperature and humidity. This suggests that management decisions within urban greenspaces are important in determining the structure of arthropod communities. Future studies on arthropods in cities should determine whether manipulating the abiotic conditions of urban greenspaces influences the composition of arthropod communities. These results should inform city planners and homeowners of the need to properly manage urban greenspaces in cities to maintain diverse arthropod assemblages.

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Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions.

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