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Trends in Microbiology Jan 2016Fungal pathogens pose serious threats to human, plant, and ecosystem health. Improved diagnostics and antifungal strategies are therefore urgently required. Here, we... (Review)
Review
Fungal pathogens pose serious threats to human, plant, and ecosystem health. Improved diagnostics and antifungal strategies are therefore urgently required. Here, we review recent developments in online bioinformatic tools and associated interactive data archives, which enable sophisticated comparative genomics and functional analysis of fungal pathogens in silico. Additionally, we highlight cutting-edge experimental techniques, including conditional expression systems, recyclable markers, RNA interference, genome editing, compound screens, infection models, and robotic automation, which are promising to revolutionize the study of both human and plant pathogenic fungi. These novel techniques will allow vital knowledge gaps to be addressed with regard to the evolution of virulence, host-pathogen interactions and antifungal drug therapies in both the clinic and agriculture. This, in turn, will enable delivery of improved diagnosis and durable disease-control strategies.
Topics: Computational Biology; Fungi; Gene Expression Regulation, Fungal; Genome, Fungal; Genomics; Host-Pathogen Interactions; Humans; Mycoses; Plant Diseases; Virulence
PubMed: 26549580
DOI: 10.1016/j.tim.2015.09.008 -
Frontiers in Cellular and Infection... 2018Iron is an absolute requirement for both the host and most pathogens alike and is needed for normal cellular growth. The acquisition of iron by biological systems is... (Review)
Review
Iron is an absolute requirement for both the host and most pathogens alike and is needed for normal cellular growth. The acquisition of iron by biological systems is regulated to circumvent toxicity of iron overload, as well as the growth deficits imposed by iron deficiency. In addition, hosts, such as humans, need to limit the availability of iron to pathogens. However, opportunistic pathogens such as are able to adapt to extremes of iron availability, such as the iron replete environment of the gastrointestinal tract and iron deficiency during systemic infection. has developed a complex and effective regulatory circuit for iron acquisition and storage to circumvent iron limitation within the human host. As can form complex interactions with both commensal and pathogenic co-inhabitants, it can be speculated that iron may play an important role in these interactions. In this review, we highlight host iron regulation as well as regulation of iron homeostasis in . In addition, the review argues for the need for further research into the role of iron in polymicrobial interactions. Lastly, the role of iron in treatment of infection is discussed.
Topics: Candida albicans; Candidiasis; Gastrointestinal Tract; Gene Expression Regulation, Fungal; Homeostasis; Host-Pathogen Interactions; Humans; Immunity; Iron; Microbial Interactions; Symbiosis; Virulence
PubMed: 29922600
DOI: 10.3389/fcimb.2018.00185 -
Proceedings of the National Academy of... Nov 2023The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can...
The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of is yet to be fully realized.
Topics: Animals; Humans; Swine; Streptococcal Infections; Farms; Swine Diseases; Virulence; Streptococcus suis; Livestock
PubMed: 37963246
DOI: 10.1073/pnas.2307773120 -
Parasite Immunology Feb 2023We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune... (Review)
Review
We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune defences to clear infecting fungal cells versus the success of the fungus in mounting compensatory adaptive responses. As each seeks to gain advantage during these skirmishes, the interactions between host and fungal pathogen are complex and dynamic. Nevertheless, simply compromising the physiological robustness of fungal pathogens reduces their ability to evade antifungal immunity, their virulence, and their tolerance against antifungal therapy. In this article I argue that this physiological robustness is based on a 'Resilience Network' which mechanistically links and controls fungal growth, metabolism, stress resistance and drug tolerance. The elasticity of this network probably underlies the phenotypic variability of fungal isolates and the heterogeneity of individual cells within clonal populations. Consequently, I suggest that the definition of the fungal Resilience Network represents an important goal for the future which offers the clear potential to reveal drug targets that compromise drug tolerance and synergise with current antifungal therapies.
Topics: Antifungal Agents; Virulence; Host-Pathogen Interactions
PubMed: 35962618
DOI: 10.1111/pim.12946 -
Fungal Genetics and Biology : FG & B Sep 2014Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with... (Review)
Review
Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. As a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. In this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. These include pathogens of both animals and plants; Ashbya gossypii, Aspergillus fumigatus, Candida albicans, Fusarium oxysporum, Magnaporthe oryzae, Ustilago maydis and Zymoseptoria tritici. We present key insights into the virulence mechanisms deployed by each species and a comparative overview of key insights obtained from genomic analysis. We then consider current trends and future challenges associated with the study of fungal pathogenicity.
Topics: Chromosomes, Fungal; Fungi; Genome, Fungal; Mitogen-Activated Protein Kinase Kinases; Secondary Metabolism; Virulence
PubMed: 25011008
DOI: 10.1016/j.fgb.2014.06.011 -
Current Opinion in Microbiology Jun 2022Bacteria live in complex communities with multiple species and strains competing with each other. Victories and defeats within these microbial wars are largely ignored... (Review)
Review
Bacteria live in complex communities with multiple species and strains competing with each other. Victories and defeats within these microbial wars are largely ignored unless they have a noticeable impact on the environment or the host, for example when a disease causing strain emerges as a winner. Evolutionary theory typically explains pathogen emergence as a trade-off between virulence and transmissibility. However, for opportunistic pathogens the secondary infection niche is often a dead end, as the host is either killed or cured, so a trade-off can not develop. In this context it is difficult to explain the maintenance of virulence genes in the population as they would be costly. Here, current literature is synthesized to address this apparent conundrum. The potential for adaptations to one niche to provide a benefit in another is described for some pathogenic species and this paradigm is extended to include genetic diversity and competition among individual strains. Finally, considering assemblages of strains in fluctuating immune environments with complex micro-niche structure, a scenario is presented in which commensal organisms can be primed for invasive disease should the opportunity arise.
Topics: Adaptation, Physiological; Host-Pathogen Interactions; Virulence
PubMed: 35168173
DOI: 10.1016/j.mib.2022.01.009 -
Cell Host & Microbe May 2016Protozoan parasites colonize numerous metazoan hosts and insect vectors through their life cycles, with the need to respond quickly and reversibly while encountering... (Review)
Review
Protozoan parasites colonize numerous metazoan hosts and insect vectors through their life cycles, with the need to respond quickly and reversibly while encountering diverse and often hostile ecological niches. To succeed, parasites must also persist within individuals until transmission between hosts is achieved. Several parasitic protozoa cause a huge burden of disease in humans and livestock, and here we focus on the parasites that cause malaria and African trypanosomiasis. Efforts to understand how these pathogens adapt to survive in varied host environments, cause disease, and transmit between hosts have revealed a wealth of epigenetic phenomena. Epigenetic switching mechanisms appear to be ideally suited for the regulation of clonal antigenic variation underlying successful parasitism. We review the molecular players and complex mechanistic layers that mediate the epigenetic regulation of virulence gene expression. Understanding epigenetic processes will aid the development of antiparasitic therapeutics.
Topics: Animals; Gene Expression Regulation; Humans; Parasites; Virulence
PubMed: 27173931
DOI: 10.1016/j.chom.2016.04.020 -
Biochemical Society Transactions Feb 2019Metal ions fulfil a plethora of essential roles within bacterial pathogens. In addition to acting as necessary cofactors for cellular proteins, making them indispensable... (Review)
Review
Metal ions fulfil a plethora of essential roles within bacterial pathogens. In addition to acting as necessary cofactors for cellular proteins, making them indispensable for both protein structure and function, they also fulfil roles in signalling and regulation of virulence. Consequently, the maintenance of cellular metal ion homeostasis is crucial for bacterial viability and pathogenicity. It is therefore unsurprising that components of the immune response target and exploit both the essentiality of metal ions and their potential toxicity toward invading bacteria. This review provides a brief overview of the transition metal ions iron, manganese, copper and zinc during infection. These essential metal ions are discussed in the context of host modulation of bioavailability, bacterial acquisition and efflux, metal-regulated virulence factor expression and the molecular mechanisms that contribute to loss of viability and/or virulence during host-imposed metal stress.
Topics: Bacteria; Host-Pathogen Interactions; Ions; Metals; Virulence
PubMed: 30626704
DOI: 10.1042/BST20180275 -
Current Pharmaceutical Biotechnology 2015Through many millennia of continuous evolution hosts and microorganisms have developed sophisticated and sometimes extremely complex mechanisms of coexisting through... (Review)
Review
Through many millennia of continuous evolution hosts and microorganisms have developed sophisticated and sometimes extremely complex mechanisms of coexisting through symbiosis and mutualism. It is now known that in humans, the population of commensal bacteria on or inside the body significantly outnumbers the host cells. Despite their numerical superiority, microorganisms have adjusted their physiological clocks to benefit themselves and at the same time their host through the maintenance of a healthy state. This very fine and multifaceted balance can be disrupted occasionally through the introduction of pathogens in the commensal bacterial population. The equilibrium is then perturbed to promote dysbiosis and the onset of disease. Through myriads of interactions within their host milieu, bacterial pathogens have developed mechanisms to sense bacterial or host-derived signalling molecules and adjust their physiology accordingly to favour their survival and propagation within their host. At the same time, the host has evolved systems to interfere with bacterial signalling in such a way as to support pathogen clearing and re-establishment of the balance. An example of a captivating interaction is the one involving the catecholamine hormones adrenaline and noradrenaline. This article will summarise the major findings involving host pathogen communication through bacterial or host-derived molecules and discuss ways to take advantage of our potential to interfere with this intricate signalling to profit the host and prolong a healthy life.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Hormones; Host-Pathogen Interactions; Humans; Quorum Sensing; Virulence
PubMed: 25420724
DOI: 10.2174/1389201015666141122205132 -
ACS Infectious Diseases Jan 2020Natural products from microorganisms are important small molecules that play roles in various biological processes like cellular growth, motility, nutrient acquisition,... (Review)
Review
Natural products from microorganisms are important small molecules that play roles in various biological processes like cellular growth, motility, nutrient acquisition, stress response, biofilm formation, and defense. It is hypothesized that pathogens exploit these molecules to regulate virulence and persistence during infections. Here, we present selected examples of signaling natural products from human pathogenic bacteria that use these metabolites to gain a competitive advantage. Targeting these signaling systems provides novel strategies to antimicrobial treatments.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Biological Products; Host Microbial Interactions; Humans; Secondary Metabolism; Signal Transduction; Virulence
PubMed: 31617342
DOI: 10.1021/acsinfecdis.9b00286