Antibiotic-mediated microbial community restructuring is dictated by variability in antibiotic-induced lysis rates and population interactions

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

It is widely known that faster-growing bacterial cells are more susceptible to many antibiotics. Given this notion, it appears intuitive antibiotic treatment would enrich slower-growing in a clonal population or populations microbial community, which has been commonly observed. However, experimental observations also show the enrichment of subpopulations under certain conditions. Does apparent discrepancy suggest uniqueness about different growth environments role additional confounding factors? If so, what could be major determinant antibiotic-mediated community restructuring? Combining modeling and quantitative measurements using barcoded heterogeneous E. coli library, we outcome restructuring can driven by two factors. One variability among responses antibiotic; other their interactions. Our results importance individual clones predicting antibiotics addressing subpopulation Antibiotic usually selects for fast-growing cells, but not always case. Here, Kim et al. antibiotic-induced changes communities depend on lysis kinetics inter-population interactions, lead outcomes.

Language: Английский

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Evolutionary shift of a tipping point can precipitate, or forestall, collapse in a microbial community

Nature Ecology & Evolution, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

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Interspecies interaction reduces selection for antibiotic resistance in Escherichia coli

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: March 27, 2023

Abstract Evolution of microbial traits depends on the interaction a species with its environment as well other coinhabiting species. However, our understanding evolution specific traits, such antibiotic resistance in complex environments is limited. Here, we determine role interspecies interactions dynamics nitrofurantoin (NIT) selection among Escherichia coli . We created synthetic two-species community comprised two variants E. (NIT susceptible and resistant) Bacillus subtilis minimal media glucose sole carbon source. show that presence B. significantly slows down for resistant mutant when NIT present this slowdown not due to competition resources. Instead, dampening enrichment largely mediated by extracellular compounds produced peptide YydF playing significant role. Our results only demonstrate impact but also importance using systems unravelling relevant mechanisms affecting resistance. This finding implies should be considered better understand predict clinic nature.

Language: Английский

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Multistability driven by cooperative growth in microbial communities

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract Microbial communities often exhibit more than one possible stable composition for the same set of external conditions 1-7 . In human microbiome, persistent changes in species and abundance are associated with health disease states 8 The main drivers these alternative remain relatively unknown 9 Here we experimentally demonstrate that a cross-kingdom community, composed six relevant to respiratory tract, displays four each dominated by different species. pairwise coculture, observe widespread bistability among pairs, providing natural origin multistability full community. contrast common association between antagonism, experiments reveal many positive interactions within community members. We find multiple display self-facilitation, or cooperative growth, modeling predicts this could drive observed as well non-canonical outcomes. A tailored biochemical screening assay reveals glutamate supplementation either reduces eliminates cooperativity growth several species, confirm such extent across pairs Our findings provide mechanistic explanation how rather competitive can underlie microbial communities.

Language: Английский

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Antibiotic-mediated microbial community restructuring is dictated by variability in antibiotic susceptibility and population interactions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 18, 2024

It is widely known that faster-growing bacterial cells are more susceptible to antibiotics. Given this notion, it appears intuitive antibiotic treatment would enrich slower-growing in a clonal population or populations microbial community, which has been commonly observed. However, experimental observations also show the enrichment of subpopulations under certain conditions. Does apparent discrepancy suggest uniqueness about different growth environments role additional confounding factors? If so, what could be major determinant antibiotic-mediated community restructuring? Combining modeling and quantitative measurements using barcoded heterogeneous E. coli library, we outcome restructuring can driven by two factors. One variability among responses antibiotic; other their interactions. Our results importance individual clones predicting antibiotics addressing subpopulation

Language: Английский

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ATP burst is the dominant driver of antibiotic lethality in Mycobacteria

Published: Sept. 27, 2024

Antibiotic-tolerant bacteria, due to their unique physiology, are refractory antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work, limits our understanding partial resistance phenotypic tolerance in mycobacteria, a driver developing genetic resistance. Using proteomics, 13 C isotopomer analysis, biochemical assays, we investigated the physiological response M. smegmatis challenged with aminoglycoside fluoroquinolone antibiotics. Two distinct classes elicited remarkably similar responses increased flux through TCA cycle, causing enhanced respiration, ROS generation, ATP burst. We observed that excessive levels not ROS, dominantly contributes cidality, which may part be, conferred by sequestration divalent metal ions ATP. Consequently, isotope tracing indicated cycle deviation from its oxidative arm as bacterial adaptive mechanism, also included activated intrinsic higher propensity develop antibiotic Our study provides new intricate mechanisms antibiotic-induced cell death expands current paradigm action.

Language: Английский

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Linking spatial drug heterogeneity to microbial growth dynamics in theory and experiment

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract Diffusion and migration play pivotal roles in microbial communities - shaping, for example, colonization new environments the maintenance of spatial structures biodiversity. While previous research has extensively studied free diffusion, such as range expansion, there remains a gap understanding effects biologically or physically eleterious confined environments. In this study, we examine interplay between drug heterogeneity within an experimental meta-community E. faecalis , Gram-positive opportunistic pathogen. When community is to spatially-extended habitats (‘islands’) bordered by deleterious conditions, find that population level response depends on trade-off growth rate island transfer into regions with harsher phenomenon explore modulating antibiotic concentration island. heterogeneous islands, composed spatially patterned patches support varying levels growth, population’s fate critically specific arrangement these same averaged leads diverging responses. These results are qualitatively captured simple simulations, analytical expressions which derive using first-order perturbation approximations reaction-diffusion models explicit dependence. Among all possible arrangements, our theoretical findings reveal highest rates at center most effectively mitigates decline, while lowest least effective. They thus serve optimal arrangements bounding mixed phase, where outcomes emerge tuning arrangements. Extending approach more complex varied structures, ring-structured community, further validates impact arrangement. Our suggest approaches interpreting clinical when applying identical doses inform optimization spatially-explicit dosing strategies. Author summary develop automated platform experimentally investigate short-term dynamics under heterogeneity. collective can vary significantly, even dose, due different By constructing model, observed simulated closely matches data. Furthermore, aligns well long-term rate, defined largest eigenvalue, system quickly enters equilibrium state. Using concepts from theory, derived relationship boundary diffusion effect, homogeneous effect. highlight habitats, emergent property. The bacterial near equilibrium, suggesting measured ecological scale may be used predict resistance evolutionary behavior.

Language: Английский

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ATP burst is the dominant driver of antibiotic lethality in Mycobacteria

Published: Sept. 27, 2024

Antibiotic-tolerant bacteria, due to their unique physiology, are refractory antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work, limits our understanding partial resistance phenotypic tolerance in mycobacteria, a driver developing genetic resistance. Using proteomics, 13 C isotopomer analysis, biochemical assays, we investigated the physiological response M. smegmatis challenged with aminoglycoside fluoroquinolone antibiotics. Two distinct classes elicited remarkably similar responses increased flux through TCA cycle, causing enhanced respiration, ROS generation, ATP burst. We observed that excessive levels not ROS, dominantly contributes cidality, which may part be, conferred by sequestration divalent metal ions ATP. Consequently, isotope tracing indicated cycle deviation from its oxidative arm as bacterial adaptive mechanism, also included activated intrinsic higher propensity develop antibiotic Our study provides new intricate mechanisms antibiotic-induced cell death expands current paradigm action.

Language: Английский

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ATP burst is the dominant driver of antibiotic lethality in Mycobacteria

Published: Nov. 29, 2024

Antibiotic-tolerant bacteria, due to their unique physiology, are refractory antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work, limits our understanding partial resistance phenotypic tolerance in mycobacteria, a driver developing genetic resistance. Using proteomics, 13 C isotopomer analysis, biochemical assays, we investigated the physiological response M. smegmatis challenged with aminoglycoside fluoroquinolone antibiotics. Two distinct classes elicited remarkably similar responses increased flux through TCA cycle, causing enhanced respiration, ROS generation, ATP burst. We observed that excessive levels not ROS, dominantly contributes cidality, which may part be, conferred by sequestration divalent metal ions ATP. Consequently, isotope tracing indicated cycle deviation from its oxidative arm as bacterial adaptive mechanism, also included activated intrinsic higher propensity develop antibiotic Our study provides new intricate mechanisms antibiotic-induced cell death expands current paradigm action.

Language: Английский

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Antibiotic effects on microbial communities are modulated by resource competition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 4, 2022

ABSTRACT Antibiotic treatment significantly impacts the human gut microbiota, but quantitative understanding of how antibiotics affect community diversity is lacking. Here, we build on classical ecological models resource competition to investigate responses antibiotic-induced species-specific death rates. Our analyses highlight complex dependence species coexistence that can arise from interplay and antibiotic activity, independent other biological mechanisms. We show cause richness change non-monotonically as concentrations are increased. identified structures depend order sequential application (non-transitivity), emergence synergistic antagonistic effects under simultaneous multiple (non-additivity). These behaviors be prevalent, especially when generalist consumers targeted. Communities prone either synergism or antagonism, typically not both, antagonism more common. Furthermore, identify a striking overlap in lead non-transitivity during sequences those non-additivity combination, suggesting our analysis broadly applicable across wide range clinically relevant schemes. In sum, results will facilitate engineering dynamics via deleterious agents.

Language: Английский

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