Primrose P E Freestone

University of Leicester | LE · Department of Infection, Immunity and Inflammation

Background: Patients with chronic obstructive pulmonary disease (COPD) experience respiratory exacerbations, many of which are associated with rhinoviruses. Current treatment strategies do not target the pathogenic rhinovirus trigger. Research question: What is the immediate effect of rhinovirus on the ciliated respiratory epithelium and can viral...

Catecholamine stress hormones (norepinephrine, epinephrine and dopamine) are signals that have been shown to be used as environmental cues which affect the growth and virulence of normal microbiota as well as pathogenic bacteria. It has been reported that Escherichia coli and Salmonella use the two-component system proteins QseC and QseE to recogni...

Microbes acquire unique lifestyles under different environmental conditions. Although this is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge.

Peritoneal dialysis (PD) may lead to infection, which could cause dialysis failure. Estimates of infectious peritonitis rate, identification of causative microbes, and infection outcomes are scarcely reported in Saudi Arabia. We conducted this study to provide epidemiological data as a geographical reference for PD-associated peritonitis. Epidemiol...

The accessory genomes of many pathogenic bacteria include ABC transporters that scavenge metal by siderophore uptake and ABC transporters that contribute to antimicrobial resistance by multidrug efflux. There are mechanistic and recently recognized structural similarities between siderophore importer proteins and efflux pumps. Here we investigated...

The accessory genome of many pathogenic bacteria includes ABC transporters that scavenge metal by siderophore uptake and ABC transporters that contribute to antimicrobial resistance by multidrug efflux. There are mechanistic and recently recognised structural similarities between siderophore importer proteins and efflux pumps. Here we investigated...

Background Infectious peritonitis is a clinically important condition contributing to the significant mortality and morbidity rates observed in peritoneal dialysis (PD) patients. Although some of the socioeconomic risk factors for PD-associated peritonitis have been identified, it is still unclear why certain patients are more susceptible than othe...

Fresh salad produce such as lettuce and spinach are an important part of a healthy diet, but are increasingly becoming associated with infection from foodborne pathogens such as Salmonella enterica. This review examines the incidence and origins of Salmonella fresh salad leaf colonization, models the behaviour of the pathogen when within a bagged s...

Importance: Salad leaves are an important part of a healthy diet, but in recent years have been associated with a growing risk of food poisoning from bacterial pathogens such as Salmonella enterica Although this is considered a significant public health problem, very little is known about what happens to the behaviour of the Salmonella when in the...

The human body is home to trillions of microorganisms which are increasingly being shown to have significant effects on a variety of disease states. Evidence exists that a bidirectional communication is taking place between us and our microbiome co-habitants, and that this dialogue is capable of influencing our health in a variety of ways. This rev...

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex (BCC) group of bacteria. It is an opportunistic Gram-negative aerobic plant pathogen that causes severe respiratory infections in cystic fibrosis (CF) patients. Infection with the Bcc and other respiratory bacteria leads to long term lung damage for the CF sufferer, which can...

Background Host signals are being shown to have a major impact on the bacterial phenotype. One of them is the endogenously produced catecholamine stress hormones, which are also used therapeutically as inotropes. Recent work form our laboratories have found that stress hormones can markedly increase bacterial growth and virulence. This report revea...

Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence...

Acquisition of iron from the key innate immune defence proteins such as transferrin and lactoferrin is an important mechanism by which pathogenic bacteria obtain essential iron for growth within their host. Bacterial species that do not produce siderophores often use specific transferrin binding proteins, the best characterised being the Neisseriac...

Previous analyses of luxS in Escherichia coli have used different strain backgrounds and design formats to produce the luxS mutation, resulting in luxS mutants with confusingly dissimilar phenotypes. This study therefore investigates the roles that strain background and mutational design strategy have upon the phenotype of the pathogenic E. coli lu...

It is clear that a dialogue is occurring between microbes and their hosts and that chemical signals are the language of this interkingdom communication. Microbial endocrinology shows that, through their long coexistence with animals and plants, microorganisms have evolved sensors for detecting eukaryotic hormones, which the microbe uses to determin...

Introduction Infection and inflammation are implicated in the pathophysiology of Bronchiolitis Obliterans Syndrome (BOS), the major cause of mortality following lung transplantation. It is unclear if the cytokine and chemokine release by Cystic Fibrosis (CF) airway epithelium in response to pathogens differs from that of the transplanted lung. Ai...

Background: Ventilated patients receiving intensive care are at significant risk of acquiring a ventilator-associated pneumonia that is associated with significant morbidity and mortality. Despite intensive research, it is still unclear why Pseudomonas aeruginosa, a microbe that rarely causes pneumonia outside of intensive care, is responsible for...

Microbial Endocrinology is a new microbiology research discipline that represents the intersection of microbiology and endocrinology with neurophysiology. It has as its main tenet that through their long co-existence with animals and plants, micro-organisms have evolved sensory systems for detecting host-associated hormones. These sensing systems a...

The feed efficiency of ruminant meat and dairy livestock can be significantly influenced by factors within their living environments. In particular, events perceived by the animals as stressful (such as parturition, transport or handling) have been found to affect susceptibility to infection. It has been well documented that even minor stress such...

Iron is essential for the growth of most bacteria, and its availability can determine the outcome of an infection. Pathogenic bacteria have evolved a variety of mechanisms to acquire this essential nutrient from host iron sequestering proteins such as transferrin and lactoferrin. Recently, this array of bacterial iron scavenging mechanisms has also...

Patients in hospital intensive care units have long been recognized as being at high risk for developing infections from bacteria, fungi, and viruses from within the hospital locality. Risk factors for development of nosocomial infections have usually focussed on the patient’s physical condition and the number and type of invasive medical procedure...

The ability of catecholamine stress hormones and inotropes to stimulate the growth of infectious bacteria is now well established. A major element of the growth induction process has been shown to involve the catecholamines binding to the high-affinity ferric-iron-binding proteins transferrin (Tf) and lactoferrin, which then enables bacterial acqui...

Cited By (since 1996): 9, Export Date: 25 August 2011, Source: Scopus, CODEN: JOBAA, doi: 10.1128/JB.01028-09, PubMed ID: 19820086, Language of Original Document: English, Correspondence Address: Freestone, P. P.; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester, United Kingdom; email: ppef1@le...

Microbial endocrinology represents a newly emerging interdisciplinary field that is formed by the intersection of the fields of neurobiology and microbiology. It is the intent of this book to introduce a new perspective to the current understanding not only of the factors that mediate the ability of microbes to cause disease, but also to the mechan...

Stress has long been correlated with susceptibility to microbial infection. One explanation for this phenomenon is the ability of pathogens to sense and respond to host stress-related catecholamines, such as norepinephrine (NE). In Gram-negative enteric pathogens, it has been proposed that NE may facilitate growth by mediating iron supply, or it ma...

Some bacterial pathogens directly respond to stress-induced neuroendocrine hormones, reacting to stress in parallel to host immune cells. • When catecholaminergic nerves within the gut release norepinephrine, the local population of gram-negative bacteria, mainly Escherichia coli, increases by as much as 105-fold. • Because catecholamines enhance b...

Among the different extracellular virulence factors produced by Pseudomonas aeruginosa are exotoxin A (ETA) and the pyoverdine and pyochelin siderophores. Production of ETA and the siderophores requires the function of the iron-starvation sigma factor PvdS, the transcriptional activator RegA, and the AraC-activator PchR. Iron represses the producti...

A holistic approach to understanding the mechanisms by which stress influences the pathogenesis of infectious disease has resulted in the development of the field of microbial endocrinology. This transdisciplinary field represents the intersection of microbiology with mammalian endocrinology and neurophysiology, and is based on the tenet that micro...

This chapter provides an overview of microbial endocrinology. Microbial Endocrinology is an interdisciplinary research field that represents the intersection of microbiology, endocrinology and neurophysiology. It is directed at providing a new paradigm to examine and understand the ability of microorganisms to interact with a host under various phy...

The dietary constituents that may act, in the broadest sense, as co-factors to enable bacterial enteropathogens to replicate in gastrointestinal environments are still largely unknown. Recent work has demonstrated that certain non-nutritional components of food, such as the catecholamines, can contribute to the ability of Gram-negative pathogens to...

A pathogenic role for Streptococcus (S) pyogenes infections in chronic plaque psoriasis is suspected but poorly defined. We separated cellular and supernatant proteins from S. pyogenes cultures by high-resolution two-dimensional gel electrophoresis, and used immunoblotting to demonstrate the diversity of serum or plasma IgGs that react with element...

Cited By (since 1996): 21, Export Date: 25 August 2011, Source: Scopus, CODEN: FMLED, doi: 10.1111/j.1574-6968.2006.00619.x, PubMed ID: 17229058, Language of Original Document: English, Correspondence Address: Lyte, M.; Department of Pharmacy Practice, Texas Tech. University Health Sciences Center, 601 4th street, STOP 8182, Lubbock, TX 79430-8162,...

The ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative bacterial adrenergic and/or dopaminergic receptor(s) to which catecholamines (norepinephrine, epinephrine and dopamine) may bind and exert their effects, or even whether the...

Drugs commonly used in intensive care settings were assayed for their ability to affect the growth of Staphylococcus epidermidis in a minimal salts medium containing 30% serum. Of 28 compounds tested, the inotropic catecholamines adrenaline, dobutamine, dopamine, isoprenaline and noradrenaline significantly stimulated bacterial growth. These drugs,...

Psychological stress is known to increase the circulating levels of the catecholamine hormones noradrenaline and adrenaline, which have been shown to influence the growth of a large number of bacterial species by acting in a siderophore-like manner or by inducing the production of novel autoinducers of growth. As we have previously demonstrated tha...

Cited By (since 1996): 93, Export Date: 25 August 2011, Source: Scopus, CODEN: CMIRE, doi: 10.1128/CMR.16.3.365-378.2003, PubMed ID: 12857773, Language of Original Document: English, Correspondence Address: Clarke, S.C.; Scottish Meningococcus/P. Ref. Lab., Department of Microbiology, Stobhill Hospital, Glasgow G21 3UW, United Kingdom; email: stuar...

Exposure of bacteria to members of the stress-associated family of catecholamine hormones, principally norepinephrine, has been demonstrated to increase both growth and production of virulence-related factors. Mutation of genes for enterobactin synthesis and uptake revealed an absolute requirement for enterobactin in norepinephrine-stimulated growt...

Bacterial colonisation of indwelling medical devices by coagulase-negative staphylococci is a prevalent risk in intensive-care units. Factors determining biofilm formation and progression to catheter- related infection are incompletely understood. We postulated that administration of inotropic agents via indwelling intravenous catheters may stimula...

Trauma is well recognized to result in the immediate and sustained release of stress-related neurochemicals such as the catecholamine norepinephrine. Past work has shown that in addition to their ability to function as neurotransmitters, catecholamines can also directly stimulate the growth of a number of pathogenic bacteria. The development of tra...

Microorganisms possess the ability to recognize hormones within the host and utilize them to adapt to their surroundings. Noradrenaline and adrenaline, which are released during human stress responses, may act as environmental cues to alter the growth of individual organisms within subgingival biofilms. The aims of this study were to modify, for an...

Salmonella enterica serovar Typhimurium and enterohemorrhagic Escherichia coli were stressed by prolonged incubation in water microcosms until it was no longer possible to observe colony formation when samples were plated on nonselective medium. Overnight incubation of samples in nutrient-rich broth medium supplemented with growth factors, however,...

Diarrhoeagenic Escherichia coli remains an important cause of diarrhoeal disease worldwide. In terms of global public health, enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli are the most important. However, enterohaemorrhagic E. coli has emerged as a cause of disease in developed countries in recent years, and a number of large outbreak...

Cited By (since 1996): 53, Export Date: 25 August 2011, Source: Scopus, CODEN: SAGUA, PubMed ID: 12412628, Language of Original Document: English, Correspondence Address: Lyte, M.; Department of Surgery, Minneapolis Med. Research Foundation, Hennepin County Medical Center, 914 South Eighth Street, D3, Minneapolis, MN 55404, United States, Chemicals...

Cited By (since 1996): 29, Export Date: 25 August 2011, Source: Scopus, CODEN: FMLED, doi: 10.1016/S0378-1097(00)00523-1, PubMed ID: 11164302, Language of Original Document: English, Correspondence Address: Lyte, M.; Department of Surgery, Minneapolis Med. Research Foundation, Hennepin County Medical Center, Minneapolis, MN 55404, United States; em...

Cited By (since 1996): 69, Export Date: 25 August 2011, Source: Scopus, CODEN: JOBAA, doi: 10.1128/JB.182.21.6091-6098.2000, PubMed ID: 11029429, Language of Original Document: English, Correspondence Address: Williams, P.H.; University of Leicester, Department of Microbiology/Immunol., Medical Sciences Building, University Road, Leicester LE1 9HN,...

Growth of a wall-less, L-form of Escherichia colispecifically requires calcium, and in its absence, cells ceased dividing, became spherical, swelled, developed large vacuoles, and eventually lysed. The key cell division protein, FtsZ, was present in the L-form at a concentration five times less than that in the parental strain. One interpretation o...

The ability of norepinephrine to increase the growth of Escherichia coli in a serum-based medium has previously been shown to be due to the production of an autoinducer of growth during early log phase. Seventeen Gram-negative and 6 Gram-positive clinical isolates were examined for a similar ability to respond to norepinephrine, and to synthesise a...

Cited By (since 1996): 57, Export Date: 25 August 2011, Source: Scopus, CODEN: FMLED, doi: 10.1016/S0378-1097(99)00007-5, PubMed ID: 10079527, Language of Original Document: English, Correspondence Address: Freestone, P.P.E.; Department Microbiology/Immunology, University of Leicester, Leicester LE1 9HN, United Kingdom; email: ppef1@le.ac.uk, Chemi...

Wall-less L-forms of Escherichia coli constitute an interesting, and relatively underused, model system for numerous studies of bacterial physiology including the cell cycle, intracellular structure and protein phosphorylation. Total extracts of the L-form revealed a pattern of protein phosphorylation similar to that of an enteropathogenic strain b...

If rapid growth (rap) mutants of Escherichia coli could be obtained, these might prove a valuable contribution to fields as diverse as growth rate control, biotechnology and the regulation of the bacterial cell cycle. To obtain rap mutants, a dnaQ mutator strain was grown for four and a half days continuously in batch culture. At the end of the sel...

The phosphorylation on tyrosine of a protein in Escherichia coli both in vivo and in vitro was revealed by recognition by anti-phosphotyrosine antibodies, labelling with [gamma-32P]ATP, and phosphoamino acid analysis. This protein, which we name TypA, is the product of the o591 reading frame as revealed by N-terminal sequencing and antibody cross-r...

Transcriptional induction of the uspA gene of Escherichia coli occurs whenever conditions cause growth arrest and cells deficient in UspA survive poorly in stationary phase. We demonstrate that the product of uspA is a serine and threonine phosphoprotein. In vivo, three isoforms of UspA were detected, two of which were phosphorylated as determined...

Proteolytic cleavage of the bacterial protein toxin pneumolysin with protease It creates two fragments of 37 and 15 kDa, This paper describes the purification of these two fragments and their subsequent physical and biological characterisation, The larger fragment is directly involved in the cytolytic mechanism of this pore-forming protein,,ia memb...

In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 1...

To discover a unifying theory of biology, it is necessary first to believe in its existence and second to seek its elements. Such a theory would explain the regulation of the cell cycle, differentiation and the origin of life. Some elements of the theory may be obtained by considering both eukaryotic and prokaryotic cell cycles. These elements incl...

The gene-protein database was used to obtain the two-dimensional polyacrylamide gel coordinates of proteins phosphorylated in extracts of Escherichia coli including those phosphorylated by eukaryotic-like kinase activities. These suggest that the phosphoproteins correspond to, or co-migrate with, the product of an open reading frame at 1.3 min (Orf...

The substrates of ion- and lipid-stimulated protein kinase activity in extracts of Escherichia coli were purified by chromatography. Subsequent N-terminal sequencing suggests that these substrates include the following: a novel 80 kDa protein co-purifying with RNA polymerase but partially homologous to elongation factor G; a protein with an apparen...

Regulation of the eukaryotic cell cycle involves calcium- and lipid-stimulated kinases acting on cytoskeletal structures; there are two principal reasons for supposing that the regulation of the prokaryotic cell cycle may be fundamentally the same. First, evidence for their fundamental difference is still missing and, second, evidence for prokaryot...

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