Biology subjects

Gaze, W. H.

Publications and source records attributed to Gaze, W. H..

7 recordsLinked to original sources

bioRxiv2026

SELECT 2.0: Refined and open access SELection Endpoints in Communities of bacTeria (SELECT) method to determine concentrations of antibiotics that may select for antimicrobial resistance in the environment

Antimicrobial resistance (AMR) is a significant and growing threat to human, plant and animal health, the global economy, and food security. The One Health approach to AMR recognises the role of the environment in the evolution, emergence, and dissemination of AMR. In part, this is due to anthropogenic pollution that releases AMR organisms alongside cocktails of compounds that may select for AMR in situ, which then pose an exposure risk to humans and animals. This has spurred growing interest from cross-sectoral stakeholders in environmental risk assessment (ERA) of antibiotics, with regards to their selective potential. Many different experimental and modelling approaches have been used to determine the lowest concentration of an antibiotic that may select for AMR. Debates continue regarding which individual approach, if any, may be best for determining concentrations of antibiotics that may select for AMR, for ERA purposes. This paper contributes to this ongoing discourse by refining and using a previously published method SELECT (SELection Endpoints in Communities of bacTeria) to rapidly generate predicted no effect concentrations for resistance (PNECRs) for 32 antibiotics on the premise that reduction in growth of complex community of bacteria correlates with selection for AMR resistance genes. The database of PNECRs of antibiotics presented here is the largest generated using a single experimental, empirical approach that will aid future efforts towards creating a standardised test. PNECR data were used to conduct ERAs using measured environmental concentrations of antibiotics to rank antibiotics by potential selection risk in different environments. The experimental approach and statistical code have been made open access, with online tutorials available to facilitate other laboratories using the SELECT 2.0 method. Finally, we discuss the limitations of this approach and how these could be addressed in future studies.

microbiology↗

bioRxiv2025

CRISPR-Cas is beneficial in plasmid competition, but limited by competitor toxin-antitoxin activity when horizontally transferred

Bacteria can encode dozens of different immune systems that protect them from infection by mobile genetic elements (MGEs). MGEs themselves may also carry immune systems, such as CRISPR-Cas, to target competitor MGEs. It is unclear when this is favoured by natural selection, and whether toxin-antitoxin (TA) systems -- common competitive mechanisms carried by plasmids -- can alter their efficacy. Here, we develop and test novel theory to analyse the outcome of competition between plasmids when one carries a CRISPR-Cas system that targets the other plasmid. Our model and experiments reveal that plasmid-borne CRISPR-Cas is beneficial to the plasmid carrying it when the plasmid has not recently transferred to a new host. However, CRISPR-Cas is selected against when the plasmid carrying it transfers horizontally, if a resident competitor plasmid encodes a TA system that elicits post-segregational killing. Consistent with a TA barrier to plasmid-borne CRISPR-Cas, a bioinformatic analysis reveals that naturally occurring CRISPR-Cas-bearing plasmids avoid targeting other plasmids with TA systems. Our work shows how the benefit of plasmid-borne CRISPR-Cas is severely reduced against TA-encoding competitor plasmids, but only when plasmid-borne CRISPR-Cas is horizontally transferred. These findings have key implications for the distribution of prokaryotic defenses and our understanding of their role in competition between MGEs, and the utility of CRISPR-Cas as a tool to remove plasmids from pathogenic bacteria.

microbiology↗

bioRxiv2025

Common non-antibiotic drugs enhance selection for antimicrobial resistance in mixture with ciprofloxacin

Antimicrobial resistance (AMR) is a major health concern, and a range of antibiotic and non-antibiotic agents can select for AMR across a range of concentrations. Selection for AMR is often investigated using single compounds, however, in the natural environment and the human body, pharmaceuticals will be present as mixtures, including both non-antibiotic drugs (NADs), and antibiotics. Here, we assessed the effects of one of three NADs in combination with ciprofloxacin, a commonly used antibiotic that is often found at concentrations in global freshwaters sufficiently high to select for AMR. We used a combination of growth assays and qPCR to determine selective concentrations of mixtures and used metagenome sequencing to identify changes to the resistome and community composition. The selective concentration of ciprofloxacin was reduced from 40{micro}g/L to 10{micro}g/L in the mixtures, and mixtures showed a stronger selection for some AMR genes such as tolC and qnrB. The communities exposed to the mixtures also showed changed community compositions. These results demonstrate that NADs and ciprofloxacin are more selective than ciprofloxacin alone, and these mixtures can cause distinct changes to the community composition. This indicates that future work should consider combinations of antibiotics and NADs as drivers of AMR when considering its maintenance and acquisition.

microbiology↗

bioRxiv2024

Antimicrobial effects, and selection for AMR by non-antibiotic drugs on bacterial communities

Antimicrobial resistance (AMR) is a major threat to human, veterinary, and agricultural health. AMR can be directly selected for by antibiotics, and indirectly co-selected for by biocides and metals. Some evidence suggests that non-antibiotic drugs (NADs) can co-select for AMR, but previous work focused on exposing single model bacterial species to predominately high concentrations of NADs. Here, we determined the antimicrobial effect and selective potential of three commonly used NADs against a complex bacterial community using a combination of culture based, metagenomic, and metratranscriptomic approaches. We found that three of five NADs tested on growth significantly reduced growth of a bacterial community, although only one (17-{beta}-estradiol) selected for an AMR marker using qPCR. Whole metagenome sequencing indicated that there was no clear strong selection by NADs for antibiotic resistance genes, nor effects on community composition. However, some changes in relative abundance of metal resistance genes were observed after exposure to diclofenac, metformin, and 17-{beta}-estradiol. Together, these results indicate that the NADs tested likely do not strongly select for AMR at both clinically and environmentally relevant concentrations.

microbiology↗

bioRxiv2022

Interspecific competition can drive the loss of conjugative plasmids from a focal species in a microbial community

Plasmids are key disseminators of antimicrobial resistance genes and virulence factors, and it is therefore critical to predict and reduce plasmid spread within microbial communities. The cost of plasmid carriage is a key metric that can be used to predict plasmids ecological fate, and it is unclear whether plasmid costs are affected by growth partners in a microbial community. We carried out competition experiments and tracked plasmid maintenance using a synthetic and stable 5-species community and a broad host-range plasmid as a model. We report that both the cost of plasmid carriage and its long-term maintenance in a focal strain depended on the presence of competitors, and that these interactions were species-specific. Addition of growth partners increased the plasmid cost to a focal strain, and accordingly plasmid loss from the focal species occurred over a shorter time frame in these species combinations. We propose that the destabilising effect of interspecific competition on plasmid maintenance may be leveraged in clinical and natural environments to cure plasmids from focal strains.

microbiology↗

bioRxiv2020

Impact of trimethoprim on the river microbiome and antimicrobial resistance.

Recent evidence suggests that anthropogenic activity can increase the levels of antimicrobial resistance (AMR) in the environment. Rivers and waterways are significant examples of environmental settings that have become repositories of antibiotics and antibiotic resistance genes (ARGs). Our recent study quantified drug concentrations in freshwater samples taken at a range of sites located on the Thames catchment; the highest levels of antibiotics and other drugs were recorded downstream of waste water treatment plants (WWTPs). One specific antibiotic: Trimethoprim (TMP) was shown at elevated concentrations reaching 2000ng/L at particular sites. We have also shown a correlative relationship between the residue of TMP and the prevalence of sulfonamide antibiotic resistance genes such as sul1. Despite this, there is still no evidence of a causative relationship between TMP concentrations and the prevalence of the ARGs at river sites. The aim of the current study was to conduct in-depth analysis using a combination of large metagenomic, geospatial and chemical datasets, in order to conduct a comparison between those sites with the highest TMP and lowest TMP levels across the Thames catchment. We aimed to establish the proximity of these sites to WWTPs, their population equivalence (PE) and land coverage. A secondary aim was to investigate seasonal variation in TMP and ARGs. Exploring these factors will help to decipher the clinical relevance of ARG accumulation at river sites. A significant correlation was shown between TMP levels at river sites and their distance downstream from a WWTP. Three sites located on the Rivers Cut and Ray showed significantly higher TMP concentrations in winter compared to summer. The population equivalence (PE) for sites with the highest TMP levels was significantly higher than those with the lowest levels. The land coverage of sites with the highest TMP levels was significantly more urban/suburban than sites with the lowest TMP concentrations, which were found to be significantly more arable. Five ARGs relevant to TMP and sulfonamides were identified across the Thames catchment. The most prevalent ARG was sul1, which was significantly more prevalent in winter compared to summer. By contrast sul2 was found to be significantly more prevalent in summer compared to winter at a site on the River Coln. The prevalence of the class 1 integron marker gene (inti1) did not differ significantly by season or between sites with the highest/lowest TMP levels.

microbiology↗

bioRxiv2019

Zinc can counteract selection for ciprofloxacin resistance

Antimicrobial resistance (AMR) has emerged as one of the most pressing global threats to public health. AMR evolution occurs in the clinic but also in the environment, where low concentrations of antibiotics and heavy metals can respectively select and co-select for resistance. While the selective potential for AMR of both antibiotics and metals is increasingly well-characterized, studies exploring the combined effect of both types of selective agents are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and an isogenic ciprofloxacin-resistant Escherichia coli MG1655 strain across a gradient of ciprofloxacin concentrations in the presence and absence of Zinc cations (Zn2+). The minimal selective concentration (MSC) for ciprofloxacin resistance significantly increased up to 5-fold in the presence of Zn2+. No such effect on the MSC was found for gentamicin, an antibiotic not known to chelate zinc cations. Environmental pollution usually consists of complex mixtures of antimicrobial agents. Our findings highlight the importance of taking antagonistic as well as additive or synergistic interactions between different chemical compounds into account when considering their effect on bacterial resistance evolution.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC=\"FIGDIR/small/780981v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@9abc9eorg.highwire.dtl.DTLVardef@d54d48org.highwire.dtl.DTLVardef@1c4df88org.highwire.dtl.DTLVardef@2f67f6_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryThe minimal selective concentration for a ciprofloxacin resistant E. coli strain increases up to 5-fold in the presence of Zinc cations.

microbiology↗