Biology subjects

McNally, A.

Publications and source records attributed to McNally, A..

28 records · Page 2Linked to original sources

bioRxiv2021

Gene-gene relationships in an Escherichia coli accessory genome are linked to function and mobility

The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an Escherichia coli pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene, suggesting that cooperation is more common than conflict in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships. Data summaryAll Supplementary Data files and the Python scripts used in the analyses are available at doi.org/10.17639/nott.7103. Impact statementThe pangenome of a species encompasses the core genes encoded by all genomes, as well as the accessory genes found in only a subset. Much remains to be understood about the relationships and interactions between accessory genes; in particular, what drives pairs of genes to appear together in the same genome, or what prevents them from being in the same genome together, more often than expected by chance. How these co-occurrence and avoidance relationships develop, and what effect they have on the dynamics and evolution of the pangenome as a whole, is largely unknown. Here, we present a springboard for understanding prokaryote pangenome evolution by uncovering significant gene relationships in a model Escherichia coli pangenome. We identify mobile genetic elements and the sharing of common function as possible driving forces behind the co-occurrence of accessory genes. Furthermore, this work offers an extensive dataset from which gene relationships could be identified for any gene of interest in this E. coli accessory genome, providing a rich resource for the community.

evolutionary biology↗

bioRxiv2020

Limited and strain-specific transcriptional and growth responses to acquisition of a multidrug resistance plasmid in genetically diverse Escherichia coli lineages

Multi-drug resistant (MDR) Escherichia coli are a major global threat to human health, wherein multi-drug resistance is primarily spread by MDR plasmid acquisition. MDR plasmids are not widely distributed across the entire E. coli species, but instead are concentrated in a small number of clones. Here, we test if diverse E. coli strains vary in their ability to acquire and maintain MDR plasmids, and if this relates to their transcriptional response following plasmid acquisition. We used strains from across the diversity of E. coli, including the common MDR lineage ST131, and the IncF plasmid, pLL35, encoding multiple antibiotic resistance genes. Strains varied in their ability to acquire pLL35 by conjugation, but all were able to stably maintain the plasmid. The effects of pLL35 acquisition on cefotaxime resistance and growth also varied among strains, with growth responses ranging from a small decrease to a small increase in growth of the plasmid-carrier relative to the parental strain. Transcriptional responses to pLL35 acquisition were limited in scale and highly strain specific. We observed significant transcriptional responses at the operon or regulon level, possibly due to stress responses or interactions with resident MGEs. Subtle transcriptional responses consistent across all strains were observed affecting functions, such as anaerobic metabolism, previously shown to be under negative frequency dependent selection in MDR E. coli. Overall, there was no correlation between the magnitude of the transcriptional and growth responses across strains. Together these data suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to dissemination of this MDR plasmid in E. coli. ImportancePlasmids play a key role in bacterial evolution by transferring niche adaptive functions between lineages, including driving the spread of antibiotic resistance genes. Fitness costs of plasmid acquisition arising from the disruption of cellular processes could limit the spread of multidrug resistance plasmids. However, the impacts of plasmid acquisition are typically measured in lab-adapted strains rather than in more ecologically relevant natural isolates. Using a clinical multidrug resistance plasmid and a diverse collection of E. coli strains isolated from clinical infections and natural environments, we show that plasmid acquisition had only limited and highly strain-specific effects on bacterial growth and transcription. These findings suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to transmission of this plasmid in natural populations of E. coli.

microbiology↗

bioRxiv2019

Real-time sampling of travelers shows intestinal colonization by multidrug-resistant bacteria to be a dynamic process with multiple transient acquisitions

BackgroundAntimicrobial resistance (AMR) is highly prevalent in low- and middle-income countries (LMIC). International travel contributes substantially to the global spread of intestinal multidrug-resistant gram-negative (MDR-GN) bacteria. Of the 100 million annual visitors to LMIC, 30-70% become colonized by MDR-GN bacteria. The phenomenon has been well documented, but since sampling has only been conducted after travelers return home, data on the actual colonization process are scarce. We aimed to characterize colonization dynamics by exploring stool samples abroad on a daily basis while visiting LMIC. MethodsA group of 20 European volunteers visiting Lao Peoples Democratic Republic for three weeks provided daily stool samples and filled in daily questionnaires. Acquisition of extended-spectrum beta-lactamase-producing gram-negative bacteria (ESBL-GN) was examined by selective stool cultures followed by whole-genome sequencing (WGS) of isolates. ResultsWhile colonization rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-GN at some time point during their overseas stay, the colonization status varying day by day. WGS analysis ascribed the transient pattern of colonization to sequential acquisition of new strains, resulting in a loss of detectable colonization by the initial MDR-GN strains. All but one participant acquired multiple strains (n=2-7). Of the total of 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), some were shared by as many as four subjects. ConclusionsThis is the first study to characterize in real time the dynamics of acquiring MDR-GN during travel. Our data show multiple transient colonization events indicative of constant microbial competition.

microbiology↗

bioRxiv2019

Allelic polymorphism shapes collective phenotypes in evolving Pseudomonas aeruginosa populations

Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported, however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level (i) evolution in sputum medium selected for decreased production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant {beta}-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to {beta}-lactam antibiotics.

microbiology↗

bioRxiv2019

Genomes of a major nosocomial pathogen Enterococcus faecium are shaped by adaptive evolution of the chromosome and plasmidome

Enterococcus faecium is a gut commensal of many mammals but is also recognized as a major nosocomial human pathogen, as it is listed on the WHO global priority list of multi-drug resistant organisms. Previous research has suggested that nosocomial strains have multiple zoonotic origins and are only distantly related to those involved in human commensal colonization. Here we present the first comprehensive population-wide joint genomic analysis of hospital, commensal and animal isolates using both short- and long-read sequencing techniques. This enabled us to investigate the population plasmidome, core genome variation and genome architecture in detail, using a combination of machine learning, population genomics and genome-wide co-evolution analysis. We observed a high level of genome plasticity with large-scale inversions and heterogeneous chromosome sizes, collectively painting a high-resolution picture of the adaptive landscape of E. faecium, and identified plasmids as the main indicator for host-specificity. Given the increasing availability of long-read sequencing technologies, our approach could be widely applied to other human and animal pathogen populations to unravel fine-scale mechanisms of their evolution.

genomics↗

bioRxiv2018

Signatures of negative frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli

Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multi-drug resistant (MDR) strains of extra-intestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution towards separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonisation and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen.

microbiology↗

bioRxiv2018

Combinatorial quorum sensing in Pseudomonas aeruginosa allows for novel cheating strategies

In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) is a social trait that is exploitable by non-cooperating cheats. Previously it has been shown that by linking QS to the production of both public and private goods, cheats can be prevented from invading populations of cooperators and this has been termed a metabolic incentive to cooperate. We hypothesized P. aeruginosa could evolve novel cheating strategies to circumvent private goods metabolism by rewiring its combinatorial response to two QS signals (3O-C12-HSL and C4-HSL). We performed a selection experiment that cycled P. aeruginosa between public and private goods growth media and evolved an isolate which rewired its control of cooperative protease expression from a synergistic (AND-gate) response to dual signal input, to a 3O-C12-HSL only response. We show that this isolate circumvents metabolic incentives to cooperate and acts as a combinatorial signaling cheat, with a higher fitness in competition with its ancestor. Our results show three important principles; first, combinatorial QS allows for diverse social strategies to emerge; second, that restrictions levied by private goods are not sufficient to explain the maintenance of cooperation in natural populations and third that modifying combinatorial QS responses could result in important physiological outcomes in bacterial populations.

microbiology↗

bioRxiv2017

Phylogeographic separation and formation of sexually discreet lineages in a global population of Yersinia pseudotuberculosis

Yersinia pseudotuberculosis is a Gram negative intestinal pathogen of humans and has been responsible for several nation-wide gastro-intestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic Yersinia, Y. pestis and Y. enterocolitica allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no large-scale global population genomic analysis of Y. pseudotuberculosis has been performed. Here we present analyses of the genomes of 134 strains of Y. pseudotuberculosis isolated from around the world, from multiple ecosystems since 1960s. Our data display a phylogeographic split within the population, with an Asian ancestry and subsequent dispersal of successful clonal lineages into Europe and the rest of the world. These lineages can be differentiated by CRISPR cluster arrays, and we show that the lineages are limited with respect to inter-lineage genetic exchange. This restriction of genetic exchange maintains the discrete lineage structure in the population despite co-existence of lineages for thousands of years in multiple countries. Our data highlights how CRISPR can be informative of the evolutionary trajectory of bacterial lineages, and merits further study across bacteria.

microbiology↗

bioRxiv2017

New kids on the block: Intercontinental dissemination and transmission of newly emerging lineages of multi-drug resistant Escherichia coli with highly dynamic resistance gene acquisition.

The increase in infections as a result of multi-drug resistant strains of Escherichia coli is a global health crisis. The emergence of globally disseminated lineages of E. coli carrying ESBL genes has been well characterised. An increase in strains producing carbapenemase enzymes and mobile colistin resistance is now being reported, but to date there is little genomic characterisation of such strains. Routine screening of patients within an ICU of West China Hospital identified a number of E. coli carrying the blaNDM-5 carbapenemase gene, found to be two distinct clones, E. coli ST167 and ST617. Interrogation of publically available data shows isolation of ESBL and carbapenem resistant strains of both lineages from clinical cases across the world. Further analysis of a large collection of publically available genomes shows that ST167 and ST617 have emerged in distinct patterns from the ST10 clonal complex of E. coli, but share evolutionary events involving switches in LPS genetics, intergenic regions and anaerobic metabolism loci. These may be evolutionary events which underpin the emergence of carbapenem resistance plasmid carriage in E. coli.

microbiology↗

bioRxiv2016

The social evolution of siderophore production in Pseudomonas aeruginosa is environmentally determined.

Bacteria secrete various exoproducts whose benefits can be shared by all cells in the vicinity. The potential importance of these \"public goods\" in bacterial evolutionary ecology has been extensively studied. Cheating by siderophore-null mutants of the opportunistic pathogen Pseudomonas aeruginosa has received particular attention. The potential of siderophore mutants to attenuate virulence, and the possibility of exploiting this for clinical ends, have generated a wealth of publications. However, the possibility that genotype {middle dot} environment interactions govern the evolutionary consequences of siderophore loss has been almost entirely ignored. A review of the available literature revealed (i) widespread use of an undefined mutant as a siderophore cheat; and (ii) a reliance on experiments conducted in iron-limited minimal medium. Whole genome sequencing of the undefined mutant revealed a range of mutations affecting phenotypes other than siderophore production. We then conducted cheating assays using defined deletion mutants, grown in conditions designed to model infected fluids and tissue in CF lung infection and non-healing wounds. Depending on the environment, we found that siderophore loss could lead to cheating, simple fitness defects, or no fitness effect at all. It is therefore crucial to develop appropriate in vitro growth conditions in order to better predict the social evolution of traits in vivo.

microbiology↗