Microbial Endocrinology

Cent. Eur. J. Biol.• 6(5) • 2011 • 685-694 DOI: 10.2478/s11535-011-0067-z Central European Journal of Biology Microbial Endocrinology Mini-Review Fathima Sharaff, Primrose Freestone* Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom Received 06 May 2011; Accepted 10 August 2011 Abstract: 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 allow the microbe to determine that they are within proximity of a suitable host, and that is time to initiate expression of genes involved in host colonisation. Microbial Endocrinology therefore provides a new paradigm with which to examine and understand the interactions of micro-organisms with their host under conditions present in both health and disease. This article will focus on microbial interactions with the fight and flight family of catecholamine stress hormones. Keywords: Bacteria • Hormones • Stress • Infection © Versita Sp. z o.o. 1. Introduction: Microbial endocrinology as a means of understanding the dialogue between animals and their microflora Microbial Endocrinology is a recently recognised interdisciplinary branch of research that represents the intersection of microbiology, endocrinology with neurophysiology [1-6]. Its objective is to provide a paradigm with which to examine and understand the interaction of micro-organisms with their host in health and disease. Microbial Endocrinology has as its foundation the tenet that through their long co-existence with animals and plants, micro-organisms have evolved detection systems for detecting host-associated chemicals such as hormones. These hormone-sensors enable the microbe to determine that they are within the locality of a suitable host, and that it is time to initiate expression of genes involved in host colonisation, or in the case of pathogenic species, genes for virulence determinants. This review cannot for space reasons cover all the Microbial Endocrinology papers published, and so the reader is directed towards reference [6] which is a recently published book on the research area. Most Microbial Endocrinology investigations have concentrated on the interaction of bacteria with the hormones released during stress, such as the catecholamine fight and flight hormones adrenaline, noradrenaline and dopamine [6]. This is in part because of the interest in the long held observation that stress in humans or animals increases their risk of developing an infection [2,5,7]. While hormones released during stress (principally adrenaline and noradrenaline) have been shown to significantly reduce cell based immune function [7], Microbial Endocrinology takes the broader view and considers the impact of the stress event from the perspective of the microbe causing the infection. In the context of human and animal welfare, Microbial Endocrinology therefore provides a useful platform on which to develop a holistic understanding of the factors that shape the interactions between microbes and their animal host during episodes of stress [1-6]. 2. The spectrum of stress hormone responsive microbes The biochemical pathway for the synthesis of catecholamine stress hormones begins with L-dopa (mostly derived from dietary sources) which is converted → dopamine → noradrenaline → adrenaline (Figure 1). Noradrenaline- and dopamine- containing nerve * E-mail: ppef1@le.ac.uk 685 Unauthenticated Download Date | 9/22/17 4:26 AM Microbial Endocrinology Figure 1. Catecholamine stress hormone biosynthesis. In mammals, catecholamines are synthesized from L-Dopa, obtained from dietary sources (the amino acids tyrosine and phenylalanine). It should be noted that various co-factors needed in the pathway are not shown.) Synthesis of catecholamines is to a degree tissue specific, and phenylethanolamine N-methyltransferase, required for adrenaline synthesis, is not expressed in cells of the enteric nervous system [8]. Key: Catecholamine biosynthesis: TH – tyrosine hydroxylase; AAD – aromatic L-amino decarboxylase; DbH – dopamine b-hydroxylase; PMT – phenylethanolamine N-methyltransferase. terminals are distributed throughout the mammalian body, including the gastrointestinal tract where they make up part of the enteric nervous system (ENS) [8]. Indeed, half of the noradrenaline present within mammals is synthesised and utilised within the ENS. Within the gut, noradrenaline is released from storage within sympathetic nerve fibres within the prevertebral ganglia that innervate the gut mucosa. Dopamine is produced in a subpopulation of non-sympathetic enteric neurons located within the intestinal wall [8]. Table 1 [9-28] shows the microbes responsive to catecholamine stress hormones. What is most apparent is that the spectrum of hormone responsive microbes is weighted towards bacteria inhabiting the gastrointestinal tract, particularly species such as Escherichia coli, Salmonella, Listeria, Campylobacter, and Yersinia [9,12,13,15-18,22]. This may be related to the abundance of noradrenaline and dopamine containing nerve terminals in the ENS [8]. However, the catecholamines are physiologically ubiquitous in terms of signalling functions and are found in fluids and tissues throughout the mammalian body [8]. Thus, it might expected that bacteria occupying a variety of in vivo niches will at some point come into contact with catecholamines, and so have cause to similarly evolve sensory systems for monitoring the stress hormone levels of their host. The fact that microbes inhabiting nearly all the major regions of the body are responsive (Table 1) [9-28] seems to support this hypothesis. As well as affecting the bacteria that colonise the gut, catecholamine stress hormones have been shown to be significant growth stimulators for a number of microbes involved in respiratory infections. In serum-based culture media, log-fold increases in cell numbers of Pseudomonas aeruginosa [9,10], Klebsiella pneumoniae, [9], Bordetella pertussis and B. bronchiseptica [11], have been demonstrated. O’Neal et al. used transcriptional profiling (microarrays) to show up-regulation of genes required for host tissue attachment in Mycoplasma hyponeumoniae exposed to noradrenaline [25]. Stress is a recognised risk factor for development of human periodontal disease, an oral health problem that accounts for more tooth loss than dental caries. Oral bacteria are implicated in causing periodontitis, which is interesting as Roberts et al. [26,27] examined 686 Unauthenticated Download Date | 9/22/17 4:26 AM F. Sharaff, P. Freestone Microbial species Catecholamine Reference [19] Aeromonas hydrophila Noradrenaline Acinetobacter lwoffii Noradrenaline Bordetella bronchiseptica, B. pertussis Adrenaline, Dopamine, Noradrenaline Burkholderia Spp. Adrenaline, Dopamine, Noradrenaline [9] [11] Balasingham and Freestone (unpublished) [29] Borrelia burgdorferi Noradrenaline Campylobacter jejuni Noradrenaline [14] Citrobacter freundii, Citrobacter rodentium Noradrenaline [9,24] Enterobacter agglomerans, E. sakazaki Noradrenaline [9] Enterococcus faecalis, E. cloacae Noradrenaline Escherichia coli Adrenaline, Dobutamine Noradrenaline Hafnia alvei Noradrenaline [9] Helicobacter pylori Adrenaline, Dopamine, Noradrenaline [16] Klebsiella oxytoca, K. pneumoniae Noradrenaline Listeria monocytogenes Adrenaline, Dopamine, Noradrenaline Morganella morgani Noradrenaline [9] Mycoplasma pneumoniae Noradrenaline [25] Proteus mirabilis Noradrenaline [9] Pseudomonas aeruginosa Noradrenaline [9,10] Salmonella enterica Adrenaline, Dopamine, Noradrenaline [9] Dopamine, Isoprenaline, [9,12,13,17,18,33,35,37,38, 40-42,46,49,51,52,64,65] [9] [9,15] [9,36,43,44,50,52,64] Shigella sonnei, S. flexneri Noradrenaline Staphylococcus aureus Noradrenaline, Dopamine Staphylococcus epidermidis, S. capitis, S. saprophyticus, S. haemolyticus, S. hominis Adrenaline, Dobutamine, Noradrenaline Streptococcus dysgalactica Noradrenaline Vibrio parahaemolyticus, V. mimicus, V. vulnificus Adrenaline, Dopamine, Noradrenaline Xanthomonas maltophila Noradrenaline [9] Yersinia enterocolitica Adrenaline, Dopamine, Noradrenaline [9] [24] [9,30] Dopamine, Isoprenaline, [9,21,23,24,30] [9] [20,22] Oral bacteria Actinomyces gerenscseriae, A. naeslundii, A. odontolyticus Campylobacter gracilis Capnocytophaga sputigena, C. gingivalis Eikenella corrodens Eubacterium saburreum, Fusobacterium periodonticum, F. nucleatum subsp. Vincentii Leptotrichia buccalis Neisseria mucosa Peptostreptococcus anaerobius, P. micros Prevotella denticola, P. melaninogenica Staphylococcus intermedius Streptococcus gordonii, S. constellatus, S. mitis, S. mutans, S. sanguis Table 1. Adrenaline, Noradrenaline [26,27] Stress hormone responsive bacteria. The table shows the spectrum of catecholamine stress hormone responsive bacteria. The hormone(s) shown are those used in the studies cited. 687 Unauthenticated Download Date | 9/22/17 4:26 AM Microbial Endocrinology the response of 43 oral microbes to catecholamines and found that those periodontal pathogens most closely associated as being causative agents of gum disease showed the greatest stress hormone responsiveness. Mouth secretions such as saliva and mucus have been shown to contain stress hormones [26,27,29]. Skin-associated bacteria, particularly the coagulasenegative staphylococci, are highly responsive to catecholamine stress hormones [9,21,23]. As well as noradrenaline, adrenaline, dopamine, the structurally related inotropes dobutamine, isoprenaline, have all been shown to increase staphylococcal growth by 5-log orders or more [9,21,23]. The coagulase-negative staphylococci are of low pathogenicity, but pose a significant infection challenge for intensive care unit patients because of to their ability to colonise and form biofilms within intravenous catheters. Of particular relevance to the human clinical setting is the finding that catecholamines, which are administered via intravenous catheters, massively stimulate staphylococcal biofilm formation [21]. Later work from our laboratory also showed that the same catecholamine inotropes can in less than a day induce recovery of antibiotic-damaged staphylococci which would otherwise appear to be dead [30]. Stress hormone responsiveness is not just a feature of the microbes of mammalian hosts. Aeromonas hydrophila, a pathogen of frogs (and occasionally humans), is also stress hormone responsive [19]. Microbial Endocrinology concepts can even be extended to non-vertebrates. Lacoste et al. showed that stressing farmed oysters led to increased susceptibility to infection with Vibrio species that was directly linked to increased production of noradrenaline in the shell fish; the injection of noradrenaline into unstressed oysters also significantly increased oyster mortality to subsequent Vibrio infection [20]. 3. Catecholamine effects on bacterial growth An obvious question is what is the mechanism by which catecholamines induce bacterial growth? So far, the majority of analyses of stress hormone responsiveness have been conducted in vitro and have used a serumor blood-based culture media to reflect the host environment in which the microbe will encounter the hormone [1-4]. As a consequence, such media is usually bacteriostatic through Fe limitation caused by chelation of free iron by high affinity iron binding proteins such as transferrin [3]. Iron is essential for growth of all bacterial pathogens, and its limitation in blood and mucosal secretions via transferrin and lactoferrin represents one of the most important innate immune defences against infection [31,32]. Mechanistically, we have shown that catecholamines form complexes with transferrin and lactoferrin, weakening the normally high affinity ferric iron complex to the point of iron loss [18,33]. This enables bacteria that lack specific systems for acquiring transferrin and lactoferrin sequestered iron to obtain the Fe needed for growth in serum or blood [3]. Recent work from our laboratory used electron paramagnetic resonance spectroscopy and chemical analyses to show that catecholamine complex formation with transferrin and lactoferrin results in reduction of the iron, from ferric to ferrous, a valency for which transferrin and lactoferrin have a much lower affinity, resulting in rapid Fe loss [34]. This iron theft process by catecholamines is significant, as the growth stimulation of bacteria resulting from addition of catecholamines to serum or blood can be over 5 log orders [3,9,18,21,23]. In terms of the bacterial molecular machinery required for catecholamine growth responsiveness, siderophore synthesis and ferric iron transport are essential elements for Gram negative bacteria such as E. coli and Salmonella. Mutant strains containing disruptions in genes for enterobactin synthesis (entA, entF) or ferric-enterobactin transport (cir, IroN or tonB) did not respond to catecholamines in iron-limited serum [35,36]. It is proposed that the siderophore is required to internalise the iron removed by the catecholamine. Sandrini et al. [34] demonstrated that reduction of transferrin and lactoferrin Fe(III) by the catecholamines also allows incorporation of released Fe(II) by bacterial ferrous uptake systems. Catecholamines therefore enable bacterial pathogens that lack siderophores or specific acquisition systems for transferrin and lactoferrin- Fe to acquire the iron needed for growth in vivo. Another mechanism by which catecholamines can induce growth of Gram-negative bacteria, particularly enteric species, involves induction of a bacterial growth stimulator [9,37]. This growth stimulator was termed the NE-AI (noradrenaline-induced autoinducer) to distinguish it from homoserine lactone type autoinducers [9]. The NE-AI induces its own synthesis, is heat stable, and has cross-species functionality, inducing increases in bacterial growth to a magnitude similar to that seen with the catecholamines [9]. The mechanism by which the NE-AI stimulates growth is unsure but has been shown to be independent of transferrin or lactoferrin [35]. In terms of its production, investigations into the induction of the E. coli NE-AI suggest only a transient 4-6 hour exposure to catecholamines is needed [9,37] after which the activity induces its own synthesis. This suggests that bacteria can retain a ‘memory’ of 688 Unauthenticated Download Date | 9/22/17 4:26 AM F. Sharaff, P. Freestone their encounter with their host’s stress hormones, and that catecholamine release during a short term acute stress could have lasting and wide acting effects on the bacterial microflora long after catecholamine levels in their host have returned to normal. 4. Catecholamine effects on bacterial virulence Catecholamines such as noradrenaline have been reported to increase the production of Shiga toxins by E. coli O157:H7 [38]. Enhanced production of Shiga toxins is significant in the context of enterohaemorrhagic E. coli pathogenesis in humans, as the toxins may cause acute renal and neurological complications via damage to microvascular endothelial cells [39]. A number of in vitro reports have shown that stress hormones enhance bacterial attachment to gut tissues. Noradrenaline was shown to enhance expression of the K99 pilus adhesin of enterotoxigenic E. coli and type 1 fimbriae of commensal E. coli [40]. Vlisidou and co-workers [41] used a bovine ligated ileal loop model of infection to show that noradrenaline increased the intestinal mucosa adherence and enteropathogenicity of E. coli O157:H7. These workers also showed that noradrenaline modulation of enteritis and adherence was dependent on the ability of the E. coli O157:H7 to form attaching and effacing lesions. Similar studies by Green et al. [42] and Chen et al. [12] have also demonstrated that catecholamines can promote adherence of enteropathogens to mammalian gut tissues. Interestingly, in contrast to the Vlisidou study [40], Chen et al. found that noradrenaline could also enhance the caecal adherence of E. coli strains possessing eae (intimin, host cell tight attachment protein) and espA (type III translocator protein) mutations which were thought to render the bacteria incapable of intimate mucosal cell attachment. Research by Bansal et al. [12] demonstrated that in addition to host cell attachment, E. coli O157:H7 showed a positive chemotactic response to noradrenaline and adrenaline. Other enteric pathogens have been shown to respond to catecholamine stress hormones. Cogan et al. [14] showed that noradrenaline enhanced the growth and virulence factor expression of Campylobacter jejuni, a chicken commensal that can also infect humans. Toscano et al. [43] used a porcine model of infection to show that pre-treatment of Salmonella enterica serovar Typhimurium with noradrenaline altered its tissue dissemination. Chicks directly given noradrenaline by crop instillation had elevated levels of S. enterica serovar Enteritidis in the caeca and liver compared to un-treated control animals [44]. In addition to the catecholamines, glucocorticoid-type hormones are also released during stress [7,45] which may be significant as the adrenocorticotropic hormone has been shown to significantly increase attachment of E. coli O157:H7 to colonic mucosa [46]. A number of in vivo studies exist which show that stress can directly affect the microflora of an animal. Physical stress of mice caused by surgery (partial hepatectomy) or a short-term period of starvation induced significant increases in the number of E. coli adhering to the caecal mucosa of stressed mice compared to control animals [40]. Overgrowth of commensal E. coli, which can cause serious systemic infection, has been shown to occur in the intestines of mice exposed to psychological stressors such as restraint [47]. Recently, Bailey et al. [48] showed that psychologically stressing mice altered the microbial diversity of the gut to such an extent that it directly increased the capacity for an invading enteric pathogen (Citrobacter rodentium) to establish an infection. How is stress of the host linked to changes in the behaviour of its gut microflora? Insight into the molecular mechanisms that may be at work was first presented by Lyte and Bailey [49]. These workers used a mouse model of chemical stress involving the selective neurotoxin 6-hydroxydopamine (6-OHDA), which destroys the nerve terminals of sympathetic neurons and causes the rapid release of stored noradrenaline into the systemic circulation, including the gut, and so mimics the hormonal changes that take place during acute stress. Lyte and Bailey found that numbers of bacteria in the gastrointestinal tract (caeca) of the chemically stressed mice increased by up to 4 log-orders during the 24 hours following administration of the neurotoxin, with commensal E. coli showing the greatest increase. Binding of bacteria to the mouse caecal wall and translocation to the mesenteric lymph nodes (potentially the beginning of a gut-associated infection) were similarly increased. Within two weeks, the time required typically for regeneration of the affected neurons, bacterial counts in the gut had returned to normal. More recently, a related study by Pullinger et al. [50] that 6-OHDA treatment of pigs following post-oral inoculation with Salmonella Typhimurium produced elevated plasma noradrenaline levels and transiently but significantly, increased faecal excretion of the bacteria. Oral administration of noradrenaline to Salmonella-infected pigs also increased shedding of the Salmonella, although in contrast to the Toscano study [43], pre-treatment of the bacteria with noradrenaline had no significant effect on the outcome of the infection. Evidence for a connecting link between increased host levels of stress hormones and changes in the commensal 689 Unauthenticated Download Date | 9/22/17 4:26 AM Microbial Endocrinology microflora is suggested by the work of Freestone et al. [18], who showed that growth of commensal E. coli isolates increased by up to 5 log-orders following exposure to noradrenaline, adrenaline, dopamine and certain of their metabolites. In an attempt to define the global transcriptional response of bacteria to catecholamine exposure, a number of microarray studies have been undertaken [12,17,25,47]. Although variations in the methodologies used for the transcriptional profiling make direct comparisons between the studies difficult, overall the gene expression profiles obtained support the view that exposure to catecholamines enhances expression of genes involved in bacterial pathogenicity (such as motility, iron acquisition, and epithelial cell attachment) [12,17,25,51]. Interestingly, a very recent paper by Peterson et al. showed in vitro that stress hormone exposure enhanced the horizontal gene transfer efficiencies of a conjugative plasmid from a clinical host strain of Salmonella Typhimurium to an E. coli recipient [52]. This suggests that acute stress of the host could be a factor that influences the evolution and adaptation of their microflora, including any bacterial pathogens that might also be resident. 5. Microbial interactions with other hormones So far we have considered the various mechanisms by which catecholamine stress hormones influence bacterial infectivity. However, evidence exists to suggest that other mammalian hormones can directly influence the course of a microbial infection. For example, binding studies by Woods et al., involving the causative agent of melioidosis, Pseudomonas (Burkholderia) pseudomallei, revealed the presence of specific high affinity binding sites for insulin [53]. This might explain why for human patients with diabetes mellitus, the progression of melioidosis has been shown to be markedly influenced by serum insulin levels. Binding proteins specific for thyrotropin have been isolated from the enteric pathogen Y. enterocolitica [54]. Endogenous opioids are among the first signals to be released by mammalian tissues under stress, and it is noteworthy that P. aeruginosa responds to the opioid dynorphin with significantly increased infectivity [55]. A number of studies have demonstrated the importance of ovarian hormones on the pathogenicity of micro-organisms involved in urinogenital infections [56-58]. Yeast can respond to, and bind, steroid hormones [56], while oestrogen can significantly enhance Candida infectivity, inducing the morphological switch from yeast to the invasive hyphal form [57]. The presence of high affinity binding proteins for oestradiol in the pathogenic yeast C. albicans [58] may provide some explanations for the observed increase in the susceptibility of pregnant women to fungal infections. 6. Why should microbes recognise our stress hormones? The evolution of microorganisms came before that of vertebrates, and it has been demonstrated that what were thought to be almost exclusively vertebrate neurotransmitters are in fact widely dispersed throughout nature. In plants, catecholamines have so far been isolated from 28 species originating from 18 plant families where they are involved in fertilization and fruit and seed development [59]. Dopamine has been isolated from broad beans [60] and dopamine and noradrenaline from bananas [61]. The L-DOPA (precursor of dopamine) content of broad beans is so high that 250 g of cooked broad beans per day has successfully been used in humans to treat the symptoms of Parkinson’s disease [60,62]. Dopamine has also been detected in fungi such as Saccharomyces cerevisiae and Penicillium chrysogenum [63]. Many of the compounds isolated are not analogues of vertebrate hormones, they are chemically identical. This ubiquitous distribution of catecholamines throughout nature suggests that microorganisms in general have had ample time preceding the evolution of plants and animals to come into contact with catecholamine-like hormones, and to develop mechanisms by which to recognize them as indicators they are within proximity of a suitable host. In animals, catecholamines exert their effects by binding to specific adrenergic and dopaminergic receptors; catecholamine binding can be prevented using an antagonist specific to the catecholamine receptor [8]. Interestingly, antagonists of mammalian adrenergic and dopaminergic receptors can also block catecholamine effects in bacteria [64]. Addition of specific a- (but not b-) adrenergic receptor antagonists blocked bacterial growth responses to noradrenaline and adrenaline but did not affect growth stimulation by dopamine [64]. Conversely, dopaminergic receptor antagonists could block growth responses to dopamine but not to either adrenaline or noradrenaline [64]. This suggests that bacterial response systems exist for catecholamine recognition that possess a degree of specificity similar to that demonstrated for catecholamine receptors in animals. In terms of a bacterial catecholamine receptor, there is so far no genomic evidence for the existence of adrenergic or dopaminergic receptors in bacterial 690 Unauthenticated Download Date | 9/22/17 4:26 AM F. Sharaff, P. Freestone species. However, Clarke et al. [65] used in vitro constructs to show that noradrenaline and adrenaline were recognised by the E. coli O157:H7 two-component regulator sensor kinase QseC, leading to the proposal that this could be a bacterial receptor for these catecholamines. However, mutation of the QseC genes in Salmonella [66] did not affect bacterial responsiveness to the catecholamines adrenaline, noradrenaline and dopamine, suggesting that a different response system for the initial recognition of catecholamines may exist in this particular species. How might sensing the stress hormone levels of their host advantage a microbe? The sensitivity of gut bacteria to catecholamines may provide insight into the answer. The abundance of noradrenaline- and dopaminecontaining nerve terminals within the enteric nervous system [8] suggests a microbe inhabiting the intestinal tract is likely to come into contact with catecholamines. Stress in animals, such as being chased by a predator, will increase systemic catecholamine levels as part of the ‘fight and flight’ response [2,8]; work from Bailey et al. [47], Lyte and Bailey [49] and Pullinger et al. [50] has showed that host stress directly affects the gut microflora. Perhaps this is because enteric microbes have evolved mechanisms to sense changes in fitness of their host by monitoring its stress hormone levels? Increasing concentrations of catecholamines may signal to the bacteria that their host is less fit, and that it is time to relocate to a new home. This the bacteria do by increasing their numbers and expression of virulence factors needed for host colonisation. If the old, stressed host is not eaten after its predator chase, the capacity of the catecholamine-stimulated bacteria to cause diarrhoea and vomiting increases their chances of gaining release into the environment, and finding a new and maybe fitter host. 7. Future directions This mini-review has shown that a dialogue is continually taking place between the microflora and their host, and that hormones are the language by which this inter-kingdom communication is occurring [1-6]. In terms of practical applications of Microbial Endocrinology, it can help provide a more holistic understanding of the impacts of stress hormone release on infection susceptibility [2]. It has relevance to human health, for example in terms of appreciating stress hormone and related drug involvement in biomaterials-related infections of acutely ill patients [21,30]. Since evidence is accumulating that stress experienced by farmed livestock can increase enteric pathogen carriage and shedding, viewing animal welfare through the lens of Microbial Endocrinology could lead to improvements in animal husbandry techniques that reduce stress and consequently improve the microbiological safety of meat products [5]. In conclusion, though this review has concentrated on microbial interactions with stress-associated hormones, given the wide variety of chemical effectors that microbes inhabiting a mammalian host will encounter, Microbial Endocrinology as a field is likely to continue to evolve for many years to come. References [1] Lyte M., Microbial endocrinology and infectious disease in the 21st century, Trends in Micro., 2004, 12, 14–20 [2] Freestone P.P., Sandrini S.M., Haigh R.D., Lyte M., Microbial endocrinology: how stress influences susceptibility to infection, Trends in Micro., 2008, 16, 55-64 [3] Freestone P.P.E., Lyte M., Microbial endocrinology: experimental design issues in the study of interkingdom signalling in infectious disease, Adv. Appl. Micro., 2009, 64, 75-105 [4] Lyte M., Freestone P.P.E., Microbial Endocrinology comes of age, Microbe, 2009, 4, 169-175 [5] Freestone P.P.E, Lyte M. Stress and microbial endocrinology: prospects for ruminant nutrition, Animal 2010,4, 1248-1257 [6] Lyte M., Freestone P.P.E., Microbial Endocrinology: inter-kingdom signalling in health and infectious disease, Springer Publishers, 2010, ISBN, 978-14419-5575-3 [7] Reiche E.M., Nunes S.O., Morimoto H.K., Stress, depression, the immune system, and cancer, Lancet Oncology, 2004, 5, 617-625 [8] Furness J.B., The Enteric Nervous System, Blackwell Pub, 2006, Malden, MA [9] Freestone P.P.E, Lyte M., Haigh R.D., Williams P.H., Stimulation of bacterial growth by heat-stable norepinephrine-induced autoinducers, FEMS Micro. Letts., 1999, 172, 53-60 [10] Alverdy J., Holbrook C., Rocha F., Seiden L., Wu R.L., Musch M., et al., Gut-derived sepsis occurs when the right pathogen with the right virulence 691 Unauthenticated Download Date | 9/22/17 4:26 AM Microbial Endocrinology [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa, Ann. Surg., 2000, 232, 480-489 Anderson M., Armstrong S.K., The Bordetella Bfe system: Growth and transcriptional response to siderophores, catechols, and neuroendocrine catecholamines, J. Bact., 2006, 188, 5731-5740 Bansal T., Englert D, Lee J., Hegde M., Wood T.K., Jayaraman A., Differential effects of epinephrine, norepinephrine, and indole on Escherichia coli O157:H7 chemotaxis, colonization and gene expression, Infect. Immun., 2007, 75, 4597-4607 Chen C., Brown D.R., Xie Y., Green B.T., Lyte M., Catecholamines modulate Escherichia coli O157:H7 adherence to murine cecal mucosa, Shock, 2003, 20, 183-188 Cogan T.A., Thomas A.O., Rees L.E., Taylor A.H., Jepson M.A., Williams P.H., et al., Norepinephrine increases the pathogenic potential of Campylobacter jejuni, Gut, 2007, 56, 1060-1065 Coulanges V., Andre P., Vidon D.J., Effect of siderophores, catecholamines, and catechol compounds on Listeria spp. growth in ironcomplexed medium, Biochem. Biophys. Res. Commun., 1997, 249, 526-530 Doherty N.C., Tobias A., Watson S., Atherton J.C., The effect of the human gut-signalling hormone, norepinephrine, on the growth of the gastric pathogen Helicobacter pylori, Helicobacter, 2009, 14, 223-30 Dowd S.E., Escherichia coli O157:H7 gene expression in the presence of catecholamine norepinephrine, FEMS Micro.Letts., 2007, 273, 214-223 Freestone P.P.E., Williams P.H., Haigh R.D., Maggs A.F., Neal C.P., Lyte, M., Growth stimulation of intestinal commensal Escherichia coli by catecholamines: a possible contributory factor in trauma-induced sepsis, Shock, 2002, 18, 465-470 Kinney K.S., Austin C.E., Morton D.S., Sonnenfeld, G., Catecholamine enhancement of Aeromonas hydrophila growth, Micro. Pathogen., 1999, 26, 85-91 Lacoste A., Jalabert F., Malham S.K., Cueff A., Poulet, S.A., Stress and stress-induced neuroendocrine changes increase the susceptibility of juvenile oysters (Crassostrea gigas) to Vibrio splendidus, Appl. Environ. Micro. 2001, 67, 2304-2309 Lyte M., Freestone P.P., Neal C.P., Olson B.A., Haigh R.D., Bayston R., et al., Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes, Lancet, 2003, 361, 130-135 [22] Nakano M., Takahashi A., Sakai Y., Nakaya Y., Modulation of pathogenicity with norepinephrine related to the type III secretion system of Vibrio parahaemolyticus, J. Inf. Dis. 2007, 195, 1353–1360 [23] Neal C.P., Freestone P.P., Maggs A.F., Haigh R.D., Williams P.H., Lyte M., Catecholamine inotropes as growth factors for Staphylococcus epidermidis and other coagulase-negative staphylococci, FEMS Micro. Letts., 2001, 194, 163–169 [24] O’Donnell P.M., Aviles H., Lyte M., Sonnenfeld, G., Enhancement of in vitro growth of pathogenic bacteria by norepinephrine: importance of inoculum density and role of transferrin, Appl. Environ. Micro., 2006, 72, 5097-5099 [25] O’Neal M.J., Schafer E.R., Madsen M.L. Minion F.C., Global transcriptional analysis of Mycoplasma hyponeumoniae following exposure to norepinephrine, Microbiology, 2008, 154, 2581-2588. [26] Roberts, A., Matthews, J., Socransky, S,. Freestone, P., Williams, P., and Chapple, I., Stress and the periodontal diseases: effects of catecholamines on the growth of periodontal bacteria in vitro, Oral Micro. Immun., 2002, 17, 296-303 [27] Roberts A., Matthews J., Socransky S., Freestone P., Williams P., Chapple I., Stress and the periodontal diseases: growth responses of periodontal bacteria to Escherichia coli stress-associated autoinducer and exogenous Fe, Oral Micro. Immun., 2005, 20, 147-153 [28] Scheckelhoff M.R., Telford S.R., Wesley M., Hu L.T., Borrelia burgdorferi intercepts host hormonal signals to regulate expression of outer surface protein A, Proc. Natl. Acad. Sci. USA., 2007, 104, 7247-7252 [29] Lucero M.T., Squires A., Catecholamine concentrations in rat nasal mucus are modulated by trigeminal stimulation of the nasal cavity, Brain Research, 1998, 807, 234–236 [30] Freestone P.P.E., Haigh R.D., Lyte M. Catecholamine inotrope resuscitation of antibioticdamaged staphylococci and its blockade by specific receptor antagonists, J. Infect. Dis., 2008, 197, 2044–1052 [31] Ratledge C, Dover LG., Iron metabolism in pathogenic bacteria, Ann. Rev. Micro., 2000, 54, 881-941 [32] Krewulak K.D., Vogel H.J., Structural biology of bacterial iron uptake, Biochim. Biophys. Acta., 2008, 1778, 1781-1804 [33] Freestone P.P., Lyte M., Neal C.P., Maggs A.F., Haigh R.D., Williams P.H., The mammalian neuroendocrine hormone norepinephrine supplies iron for bacterial growth in the presence 692 Unauthenticated Download Date | 9/22/17 4:26 AM F. Sharaff, P. Freestone [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] of transferrin or lactoferrin, J. Bact., 2000, 182, 6091-6098 Sandrini S.M., Shergill R., Woodward J., Muralikuttan R., Haigh R.D., Lyte M., et al., Elucidation of the mechanism by which catecholamine stress hormones liberate iron from the innate immune defense proteins transferrin and lactoferrin, J. Bact., 2010, 192, 587-594 Freestone P.P., Haigh R.D., Williams P.H., Lyte M., Involvement of enterobactin in norepinephrinemediated iron supply from transferrin to enterohaemorrhagic Escherichia coli, FEMS Micro. Letts., 2003, 222, 39-43 Williams P.H., Rabsch W., Methner U., Voigt W., Tschäpe H., Reissbrodt R., Catecholate receptor proteins in Salmonella enterica: role in virulence and implications for vaccine development, Vaccine, 2006, 24, 840-3844 Lyte M., Frank C.D., Green, B.T., Production of an autoinducer of growth by norepinephrine cultured Escherichia coli O157:H7, FEMS Micro. Letts., 1996, 139, 155-159 Lyte M., Arulanandam B.P. Frank C.D., Production of Shiga-like toxins by Escherichia coli O157:H7 can be influenced by the neuroendocrine hormone norepinephrine, J. Lab. Clin. Med., 1996, 128, 392-398 Tarr P.I., Neill M.A., Escherichia coli O157:H7, Gastroenterol. Clin. North Am., 2001. 30, 735-751 Hendrickson B.A., Guo J., Laughlin R., Chen Y. Alverdy J.C., Increased type 1 fimbrial expression among commensal Escherichia coli isolates in the murine cecum following catabolic stress, Infect. Immun., 1999, 67, 745-753 Vlisidou I., Lyte M., Van Diemen P.M., Hawes P., Monaghan P., Wallis T.S., et al., The neuroendocrine stress hormone norepinephrine augments Escherichia coli O157:H7-induced enteritis and adherence in a bovine ligated ileal loop model of infection, Infect. Immun. 2004, 72, 5446-5451 Green B.T., Lyte M., Chen C., Xie Y., Casey M.A., Kulkarni-Narla A., et al., Adrenergic modulation of Escherichia coli O157:H7 adherence to the colonic mucosa, Am. J. Phys. – Gastrointest. Liver Physiol., 2004, 287, G1238-G1246 Toscano M.J, Stabel T.J., Bearson S.M,. Bearson B.L., Lay Jr D.C., Cultivation of Salmonella enterica serovar Typhimurium in a norepinephrinecontaining medium alters in vivo tissue prevalence in swine, J. Exp. Animal Sci., 2007, 43, 329–338 Methner U., Rabsch W., Reissbrodt R., Williams P.H., Effect of norepinephrine on colonisation [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] and systemic spread of Salmonella enterica in infected animals: Role of catecholate siderophore precursors and degradation products, Int. J. Med. Microbiol., 2008, 298, 429-39 Mishra S.K, Segal E., Gunter E., Kurup V.P., Mishra J., Murali P.S., et al., Stress, immunity and mycotic diseases, J. Med.Vet. Mycol., 1994, 32, 379-406 Schreiber K.L., Brown, D.R., Adrenocorticotrophic hormone modulates Escherichia coli O157:H7 adherence to porcine colonic mucosa, Stress, 2005, 8, 185-19. Bailey M.T., Engler H., Sheridan J.F., Stress induces the translocation of cutaneous and gastrointestinal microflora to secondary lymphoid organs of C57BL/6 mice, J.Neuroimmunol., 2006, 171, 29-37 Bailey M.T., Dowd S.E., Parry N.M., Galley J.D., Schauer D.B., Lyte, M., Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium, Infect. Immun., 2010, 78, 1509-1519 Lyte M., Bailey M.T., Neuroendocrine-bacterial interactions in a neurotoxin-induced model of trauma, J. Surg. Res., 1997, 70, 195-201 Pullinger G.D., van Diemen P.M., Carnell S.C., Davies H., Lyte M., Stevens M.P., 6-hydroxydopaminemediated release of norepinephrine increases faecal excretion of Salmonella enterica serovar Typhimurium in pigs, Vet. Res., 2010, 41, 68 Kendall M., Rasko D., Sperandio V., Global effects of the cell-to-cell signalling molecules autoinducer-2, autoinducer-3, and epinephrine in a luxS mutant of enterohemorrhagic Escherichia coli, Infect. Immun., 2007, 75, 4875-4884 Peterson G., Kumar A., Gart E., Narayanan S., Catecholamines increase conjugative gene transfer between enteric bacteria, Microb Pathog., 2011, 51, 1-8 Woods D.E., Jones A.L., Hill P.J., Interaction of insulin with Pseudomonas pseudomallei, Infect. Immun., 1993, 61, 4045-4050 Weiss M., Ingbar S.H., Winblad S. Kasper D.L., Demonstration of a saturable binding site for thyrotropin in Yersinia enterocolitica, Science, 1983, 219, 1331-1333 Zaborina O., Lepine F., Xiao G., Valuckaite V., Chen Y., Li T., et al., Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa, PLoS Pathog., 2007, 3, e35. Das M., Datta A., Steroid binding protein(s) in yeasts, Biochem. Int., 1985, 11, 171–176, Sonnex C., Influence of ovarian hormones on urogenital infection, Sex. Transm. Infect., 1998, 74, 11-19 693 Unauthenticated Download Date | 9/22/17 4:26 AM Microbial Endocrinology [58] Madani N.D., Malloy P.J., Rodriguez-Pombo P., Krishnan A.V., Feldman, D., Candida albicans estrogen-binding protein gene encodes an oxidoreductase that is inhibited by estradiol, Proc. Natl. Acad. Sci. USA,1994, 91, 922–926 [59] Roshchina V,V., Neurotransmitters in plant life, Plymouth Science Publishers, 2001 [60] Waalkes T.P., Sjoerdsma A., Creveling C.R., Weissbach H., Udenfriend S., Serotonin, norepinephrine, and related compounds in bananas, Science, 1958, 127, 648-650 [61] Rabey J.M., Vered Y., Shabtai H, Graff E, Korczyn A.D., Improvement of parkinsonian features correlate with high plasma levodopa values after broad bean (Vicia faba) consumption, J. Neuro. Neurosurg Psych., 1992, 55, 725-727 [62] Apaydin H., Broad bean (Vicia faba)––a natural source of L-DOPA––prolongs `on’ periods in patients with Parkinson’s disease who have `on–off’ fluctuations, Mov. Disord., 2000, 15, 164–166 [63] Tsavkelova E.A., Klimova S.Y., Cherdyntseva T.A., Netrusov, A.I., Hormones and hormone-like substances of microorganisms: a review, Appl. Biochem. Microbiol. (Russia), 2006, 42, 229–235 [64] Freestone P.P.E., Haigh R.D., Lyte, M., Blockade of catecholamine-induced growth by adrenergic and dopaminergic receptor antagonists in Escherichia coli O157: H7, Salmonella enterica and Yersinia enterocolitica, BMC Microbiology, 2007, 7, 8 (1-13). [65] Clarke M.B., Hughes D.T., Zhu C., Boedeker E. C., Sperandio V., The QseC sensor kinase: a bacterial adrenergic receptor, Proc. Natl. Acad. Sci. USA., 2006, 103, 10420-10425 [66] Pullinger G, Carnell SC, Farveen F, van Diemen P, Dziva F, Morgan E, Lyte, et al., Norepinephrine augments Salmonella-induced bovine enteritis in a manner associated with increased net replication but independent of the putative adrenergic sensor kinases QseC and QseE, Infect. Immun., 2010, 78, 372–380 694 Unauthenticated Download Date | 9/22/17 4:26 AM