The metabolic burden associated with plasmid acquisition: An assessment of the unrecognized benefits to host cells.

Bacterial conjugation, wherein DNA is transferred between cells through direct contact, is highly prevalent in complex microbial communities and is responsible for spreading myriad genes related to human and environmental health. Despite their importance, much remains unknown regarding the mechanisms driving the spread and persistence of these plasmids in situ. Studies have demonstrated that transferring, acquiring, and maintaining a plasmid imposes a significant metabolic burden on the host.

Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics.

Unlabelled: The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. Previous work found that the relationship between [ATP] and growth rate can account for the strength and occurrence of the inoculum effect for bactericidal antibiotics.

Selection and horizontal gene transfer underlie microdiversity-level heterogeneity in resistance gene fate during wastewater treatment.

Activated sludge is the centerpiece of biological wastewater treatment, as it facilitates removal of sewage-associated pollutants, fecal bacteria, and pathogens from wastewater through semi-controlled microbial ecology. It has been hypothesized that horizontal gene transfer facilitates the spread of antibiotic resistance genes within the wastewater treatment plant, in part because of the presence of residual antibiotics in sewage. However, there has been surprisingly little evidence to suggest that sewage-associated antibiotics select for resistance at wastewater treatment plants via horizontal gene transfer or otherwise.

Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics.

The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. We previously found that growth productivity, which captures the relationship between [ATP] and growth, can account for the strength of the inoculum effect for bactericidal antibiotics.

Sub-inhibitory antibiotic treatment selects for enhanced metabolic efficiency.

Bacterial growth and metabolic rates are often closely related. However, under antibiotic selection, a paradox in this relationship arises: antibiotic efficacy decreases when bacteria are metabolically dormant, yet antibiotics select for resistant cells that grow fastest during treatment. That is, antibiotic selection counterintuitively favors bacteria with fast growth but slow metabolism.

Tradeoff between lag time and growth rate drives the plasmid acquisition cost.

Conjugative plasmids drive genetic diversity and evolution in microbial populations. Despite their prevalence, plasmids can impose long-term fitness costs on their hosts, altering population structure, growth dynamics, and evolutionary outcomes. In addition to long-term fitness costs, acquiring a new plasmid introduces an immediate, short-term perturbation to the cell.

Interactions between metabolism and growth can determine the co-existence of and .

Most bacteria exist and interact within polymicrobial communities. These interactions produce unique compounds, increase virulence and augment antibiotic resistance. One community associated with negative healthcare outcomes consists of and .

Disturbing the Spatial Organization of Biofilm Communities Affects Expression of -Regulated Virulence Factors in Staphylococcus aureus.

Staphylococcus aureus uses quorum sensing and nutrient availability to control the expression of -regulated virulence factors. Quorum sensing is mediated by autoinducing peptide (AIP), which at a high concentration reduces expression of surface attachment proteins (, ) and increases expression of exotoxins () and proteases (). Nutrient availability can be sensed through the / system.

Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics.

Understanding the mechanisms by which populations of bacteria resist antibiotics has implications in evolution, microbial ecology, and public health. The inoculum effect (IE), where antibiotic efficacy declines as the density of a bacterial population increases, has been observed for multiple bacterial species and antibiotics. Several mechanisms to account for IE have been proposed, but most lack experimental evidence or cannot explain IE for multiple antibiotics.

Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment.

Conjugative plasmids often encode antibiotic resistance genes that provide selective advantages to their bacterial hosts during antibiotic treatment. Previous studies have predominantly considered these established genes as the primary benefit of antibiotic-mediated plasmid dissemination. However, many genes involved in cellular metabolic processes may also protect against antibiotic treatment and provide selective advantages.

Horizontal gene transfer enables programmable gene stability in synthetic microbiota.

The functions of many microbial communities exhibit remarkable stability despite fluctuations in the compositions of these communities. To date, a mechanistic understanding of this function-composition decoupling is lacking. Statistical mechanisms have been commonly hypothesized to explain such decoupling.

PHASE: An Open-Source Program for the Analysis of ase, ctivity, and leep Under ntrainment.

The problem of entrainment is central to circadian biology. In this regard, has been an important model system. Owing to the simplicity of its nervous system and the availability of powerful genetic tools, the system has shed significant light on the molecular and neural underpinnings of entrainment.

Population structure of blaKPC-harbouring IncN plasmids at a New York City medical centre and evidence for multi-species horizontal transmission.

Background: Carbapenem-resistant Enterobacterales (CRE) are highly concerning MDR pathogens. Horizontal transfer of broad-host-range IncN plasmids may contribute to the dissemination of the Klebsiella pneumoniae carbapenemase (KPC), spreading carbapenem resistance among unrelated bacteria. However, the population structure and genetic diversity of IncN plasmids has not been fully elucidated.

Assessment of Radiological Hazard of Radioactive Waste Using Effective or Organ Doses: How This May Affect Final Waste Disposal.

The radiological hazard of spent nuclear fuel and radioactive waste slows down further development of nuclear energy systems. The authors evaluate timescales required to reduce the radiological hazard of accumulated waste to the reference level of natural uranium that had been consumed by the nuclear energy system. The estimate of this time scale depends on the radiological hazard metric used in the calculations.

Phylogenomics of two ST1 antibiotic-susceptible non-clinical strains reveals multiple lineages and complex evolutionary history in global clone 1.

is an opportunistic pathogen that is difficult to treat due to its resistance to extreme conditions, including desiccation and antibiotics. Most strains causing outbreaks around the world belong to two main global lineages, namely global clones 1 and 2 (GC1 and GC2). Here, we used a combination of Illumina short read and MinION (Oxford Nanopore) long-read sequence data with a hybrid assembly approach to complete the genome sequence of two antibiotic-sensitive GC1 strains, Ex003 and Ax270, recovered in Lebanon from water and a rectal swab of a cat, respectively.

Honey bee sHSP are responsive to diverse proteostatic stresses and potentially promising biomarkers of honey bee stress.

The pollination services provided by the honey bee are critical in both natural and agricultural ecosystems. Honey bee colonies in the United States have suffered from an increased rate of die-off in recent years, stemming from a complex set of interacting stresses that remain poorly described. Defining specific common cellular processes and cellular stress responses impacted by multiple stressors represent a key step in understanding these synergies.

Quantitative Microbial Risk Assessment of Antimicrobial Resistant and Susceptible in Reclaimed Wastewaters.

The annual risks of colonization, skin infection, bloodstream infection (BSI), and disease burden from exposures to antibiotic-resistant and susceptible () were estimated using quantitative microbial risk assessment (QMRA). We estimated the probability of nasal colonization after immersion in wastewater (WW) or greywater (GW) treated across a range of treatment alternatives and subsequent infection. Horizontal gene transfer was incorporated into the treatment model but had little effect on the predicted risk.

Thermal stress induces tissue damage and a broad shift in regenerative signaling pathways in the honey bee digestive tract.

Honey bee colonies in the USA have suffered from increased die-off in the last few years with a complex set of interacting stresses playing a key role. With changing climate, an increase in the frequency of severe weather events, such as heat waves, is anticipated. Understanding how these changes may contribute to stress in honey bees is crucial.

Digital Insights Into Nucleotide Metabolism and Antibiotic Treatment Failure.

Nucleotide metabolism plays a central role in bacterial physiology, producing the nucleic acids necessary for DNA replication and RNA transcription. Recent studies demonstrate that nucleotide metabolism also proactively contributes to antibiotic-induced lethality in bacterial pathogens and that disruptions to nucleotide metabolism contributes to antibiotic treatment failure in the clinic. As antimicrobial resistance continues to grow unchecked, new approaches are needed to study the molecular mechanisms responsible for antibiotic efficacy.

Quantitative analysis of horizontal gene transfer in complex systems.

Horizontal gene transfer (HGT) plays a significant role in rapidly propagating diverse traits throughout bacterial populations, thereby accelerating natural evolution and leading to complex community structures. Critical gene transfer rates underlying these occurrences dictate the efficiency and speed of gene spread; these rates are often highly specific to HGT mechanism and environmental context, and have historically been challenging to reliably quantify. In this review, we examine recent works that leverage rigorous quantitative methods to precisely measure these rates in a variety of settings beginning with in vitro studies and advancing to in situ measurements; we emphasize contexts where quantification across multiple scales of complexity has led to fundamental biological insights.

Investigation of the prevalence and catalytic activity of rubredoxin-fused alkane monooxygenases (AlkBs).

Interest in understanding the environmental distribution of the alkane monooxygenase (AlkB) enzyme led to the identification of over 100 distinct alkane monooxygenase (AlkB) enzymes containing a covalently bound, or fused, rubredoxin. The rubredoxin-fused AlkB from Dietzia cinnamea was cloned as a full-length protein and as a truncated protein with the rubredoxin domain deleted. A point mutation (V91W) was introduced into the full-length protein, with the goal of assessing how steric bulk in the putative substrate channel might affect selectivity.

Conjugation dynamics depend on both the plasmid acquisition cost and the fitness cost.

Plasmid conjugation is a major mechanism responsible for the spread of antibiotic resistance. Plasmid fitness costs are known to impact long-term growth dynamics of microbial populations by providing plasmid-carrying cells a relative (dis)advantage compared to plasmid-free counterparts. Separately, plasmid acquisition introduces an immediate, but transient, metabolic perturbation.

Clinically relevant mutations in core metabolic genes confer antibiotic resistance.

Although metabolism plays an active role in antibiotic lethality, antibiotic resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed adapted to representative antibiotics at increasingly heightened metabolic states.

Predictive biology: modelling, understanding and harnessing microbial complexity.

Predictive biology is the next great chapter in synthetic and systems biology, particularly for microorganisms. Tasks that once seemed infeasible are increasingly being realized such as designing and implementing intricate synthetic gene circuits that perform complex sensing and actuation functions, and assembling multi-species bacterial communities with specific, predefined compositions. These achievements have been made possible by the integration of diverse expertise across biology, physics and engineering, resulting in an emerging, quantitative understanding of biological design.