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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 -
Antioxidants & Redox Signaling Feb 2018L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria, and some fungi. In contrast to other low-molecular-weight redox buffers, glutathione and... (Review)
Review
SIGNIFICANCE
L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria, and some fungi. In contrast to other low-molecular-weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological pH, which makes it resistant to autoxidation. Ergothioneine regulates microbial physiology and enables the survival of microbes under stressful conditions encountered in their natural environments. In particular, ergothioneine enables pathogenic microbes, such as Mycobacterium tuberculosis (Mtb), to withstand hostile environments within the host to establish infection. Recent Advances: Ergothioneine has been reported to maintain bioenergetic homeostasis in Mtb and protect Mtb against oxidative stresses, thereby enhancing the virulence of Mtb in a mouse model. Furthermore, ergothioneine augments the resistance of Mtb to current frontline anti-TB drugs. Recently, an opportunistic fungus, Aspergillus fumigatus, which infects immunocompromised individuals, has been found to produce ergothioneine, which is important in conidial health and germination, and contributes to the fungal resistance against redox stresses.
CRITICAL ISSUES
The molecular mechanisms of the functions of ergothioneine in microbial physiology and pathogenesis are poorly understood. It is currently not known if ergothioneine is used in detoxification or antioxidant enzymatic pathways. As ergothioneine is involved in bioenergetic and redox homeostasis and antibiotic susceptibility of Mtb, it is of utmost importance to advance our understanding of these mechanisms.
FUTURE DIRECTIONS
A clear understanding of the role of ergothioneine in microbes will advance our knowledge of how this thione enhances microbial virulence and resistance to the host's defense mechanisms to avoid complete eradication. Antioxid. Redox Signal. 28, 431-444.
Topics: Antioxidants; Ergothioneine; Homeostasis; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Oxidation-Reduction; Oxidative Stress; Virulence
PubMed: 28791878
DOI: 10.1089/ars.2017.7300 -
FEBS Letters Aug 2014A plethora of RNAs with regulatory functions has been discovered in many non-pathogenic and pathogenic bacteria. In Staphylococcus aureus, recent findings show that a... (Review)
Review
A plethora of RNAs with regulatory functions has been discovered in many non-pathogenic and pathogenic bacteria. In Staphylococcus aureus, recent findings show that a large variety of RNAs control target gene expression by diverse mechanisms and many of them are expressed in response to specific internal or external signals. These RNAs comprise trans-acting RNAs, which regulate gene expression through binding with mRNAs, and cis-acting regulatory regions of mRNAs. Some of them possess multiple functions and encode small but functional peptides. In this review, we will present several examples of RNAs regulating pathogenesis, antibiotic resistance, and host-pathogen interactions and will illustrate how regulatory proteins and RNAs form complex regulatory circuits to express the virulence factors in a dynamic manner.
Topics: Gene Expression Regulation, Bacterial; Quorum Sensing; RNA, Bacterial; Staphylococcus aureus; Transcription, Genetic; Virulence
PubMed: 24873876
DOI: 10.1016/j.febslet.2014.05.037 -
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 -
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 -
Journal of Molecular Biology Nov 2019Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course... (Review)
Review
Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course of an infection, subpopulations occur, which differ in certain virulence-relevant factors, stress adaptation functions or physiological and metabolic abilities. The mechanisms driving this heterogeneity are divergent reactions of the pathogens to differences in host tissue microenvironments. In addition, certain genetic regulatory circuits with positive feedback loops and stochastic differences in gene expression can generate endogenous fluctuations in regulatory components leading to bistable expression of virulence-associated functions. Here, we focus on the occurrence of phenotypic heterogeneity in populations of well-studied examples of pathogens, which enables cooperative, social behavior where a subpopulation of producers shares fitness- and/or virulence-relevant goods and traits with non-producers. We further highlight that this strategy allows preadaptation of a subgroup of cells to recurrent and thus predictable changes of the environment that they encounter during the different stages of the infection. The diversity within bacterial communities has a significant influence on the survival of the pathogens within their hosts and the progression of the disease.
Topics: Adaptation, Physiological; Bacteria; Bacterial Physiological Phenomena; Biological Variation, Population; Host-Pathogen Interactions; Microbiological Phenomena; Nitric Oxide; Oxidation-Reduction; Phenotype; Reactive Oxygen Species; Stress, Physiological; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 31260693
DOI: 10.1016/j.jmb.2019.06.024 -
Virulence Dec 2021Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking,... (Review)
Review
Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking, protein sorting, signal transduction, and bacterial infections. Both Gram-positive bacteria (.) and Gram-negative bacteria (, etc.) can hijack the various host-lipids and utilize them structurally as well as functionally to mount a successful infection. The pathogens can deploy with various arsenals to exploit host membrane lipids and lipid-associated receptors as an attachment for toxins' landing or facilitate their entry into the host cellular niche. Bacterial species like sp. can also modulate the host lipid metabolism to fetch its carbon source from the host. The sequential conversion of host membrane lipids into arachidonic acid and prostaglandin E2 due to increased activity of cPLA-2 and COX-2 upon bacterial infection creates immunosuppressive conditions and facilitates the intracellular growth and proliferation of bacteria. However, lipids' more debatable role is that they can also be a blessing in disguise. Certain host-lipids, especially sphingolipids, have been shown to play a crucial antibacterial role and help the host in combating the infections. This review shed light on the detailed role of host lipids in bacterial infections and the current understanding of the lipid in therapeutics. We have also discussed potential prospects and the need of the hour to help us cope in this race against deadly pathogens and their rapidly evolving stealthy virulence strategies.
Topics: Animals; Bacteria; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Host-Pathogen Interactions; Humans; Lipid Metabolism; Membrane Lipids; Mice; Signal Transduction; Virulence
PubMed: 33356849
DOI: 10.1080/21505594.2020.1869441 -
Molecular Biology of the Cell Dec 2015One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence...
One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.
Topics: Animals; Bacteria; Cell Biology; Host-Pathogen Interactions; Humans; Infections; Mice; Parasites; Signal Transduction; Virulence; Viruses
PubMed: 26628749
DOI: 10.1091/mbc.E15-03-0144