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Proceedings of the National Academy of... Apr 2022Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the...
Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the application of machine learning (ML) to whole-genome sequences (WGSs) has facilitated pathogen identification. However, relying solely on genetic information to identify emerging or new pathogens is fundamentally constrained, especially if novel virulence factors exist. In addition, even WGSs with ML pipelines are unable to discern phenotypes associated with cryptic genetic loci linked to virulence. Here, we set out to determine if ML using phenotypic hallmarks of pathogenesis could assess potential pathogenic threat without using any sequence-based analysis. This approach successfully classified potential pathogenetic threat associated with previously machine-observed and unobserved bacteria with 99% and 85% accuracy, respectively. This work establishes a phenotype-based pipeline for potential pathogenic threat assessment, which we term PathEngine, and offers strategies for the identification of bacterial pathogens.
Topics: Bacteria; Genome, Bacterial; Machine Learning; Phenotype; Virulence; Virulence Factors; Whole Genome Sequencing
PubMed: 35363569
DOI: 10.1073/pnas.2112886119 -
Advances in Experimental Medicine and... 2020Calcium (Ca) is a universal signaling ion, whose major informational role shaped the evolution of signaling pathways, enabling cellular communications and responsiveness... (Review)
Review
Calcium (Ca) is a universal signaling ion, whose major informational role shaped the evolution of signaling pathways, enabling cellular communications and responsiveness to both the intracellular and extracellular environments. Elaborate Ca regulatory networks have been well characterized in eukaryotic cells, where Ca regulates a number of essential cellular processes, ranging from cell division, transport and motility, to apoptosis and pathogenesis. However, in bacteria, the knowledge on Ca signaling is still fragmentary. This is complicated by the large variability of environments that bacteria inhabit with diverse levels of Ca. Yet another complication arises when bacterial pathogens invade a host and become exposed to different levels of Ca that (1) are tightly regulated by the host, (2) control host defenses including immune responses to bacterial infections, and (3) become impaired during diseases. The invading pathogens evolved to recognize and respond to the host Ca, triggering the molecular mechanisms of adhesion, biofilm formation, host cellular damage, and host-defense resistance, processes enabling the development of persistent infections. In this review, we discuss: (1) Ca as a determinant of a host environment for invading bacterial pathogens, (2) the role of Ca in regulating main events of host colonization and bacterial virulence, and (3) the molecular mechanisms of Ca signaling in bacterial pathogens.
Topics: Bacteria; Bacterial Infections; Calcium; Host Microbial Interactions; Humans; Virulence
PubMed: 31646536
DOI: 10.1007/978-3-030-12457-1_33 -
Molecular Genetics and Genomics : MGG Nov 2022The current pandemic (COVID-19) has made evident the need to approach pathogenicity from a deeper and more systematic perspective that might lead to methodologies to...
The current pandemic (COVID-19) has made evident the need to approach pathogenicity from a deeper and more systematic perspective that might lead to methodologies to quickly predict new strains of microbes that could be pathogenic to humans. Here we propose as a solution a general and principled definition of pathogenicity that can be practically implemented in operational ways in a framework for characterizing and assessing the (degree of) potential pathogenicity of a microbe to a given host (e.g., a human individual) just based on DNA biomarkers, and to the point of predicting its impact on a host a priori to a meaningful degree of accuracy. The definition is based on basic biochemistry, the Gibbs free Energy of duplex formation between oligonucleotides and some deep structural properties of DNA revealed by an approximation with certain properties. We propose two operational tests based on the nearest neighbor (NN) model of the Gibbs Energy and an approximating metric (the h-distance.) Quality assessments demonstrate that these tests predict pathogenicity with an accuracy of over 80%, and sensitivity and specificity over 90%. Other tests obtained by training machine learning models on deep features extracted from DNA sequences yield scores of 90% for accuracy, 100% for sensitivity and 80% for specificity. These results hint towards the possibility of an operational, objective, and general conceptual framework for prior identification of pathogens and their impact without the cost of death or sickness in a host (e.g., humans.) Consequently, a reasonable prediction of possible pathogens might pave the way to eventually transform the way we handle and prepare for future pandemic events and mitigate the adverse impact on human health, while reducing the number of clinical trials to obtain similar results.
Topics: Humans; Virulence; COVID-19; Oligonucleotides; DNA; Biomarkers
PubMed: 36125534
DOI: 10.1007/s00438-022-01951-w -
PeerJ 2022Obligate fungal pathogens (ascomycetes and basidiomycetes) and oomycetes are known to cause diseases in cereal crop plants. They feed on living cells and most of them... (Review)
Review
Obligate fungal pathogens (ascomycetes and basidiomycetes) and oomycetes are known to cause diseases in cereal crop plants. They feed on living cells and most of them have learned to bypass the host immune machinery. This paper discusses some of the factors that are associated with pathogenicity drawing examples from ascomycetes, basidiomycetes and oomycetes, with respect to their manifestation in crop plants. The comparisons have revealed a striking similarity in the three groups suggesting convergent pathways that have arisen from three lineages independently leading to an obligate lifestyle. This review has been written with the intent, that new information on adaptation strategies of biotrophs, modifications in pathogenicity strategies and population dynamics will improve current strategies for breeding with stable resistance.
Topics: Virulence; Plant Breeding; Oomycetes; Adaptation, Physiological; Ascomycota
PubMed: 36042858
DOI: 10.7717/peerj.13794 -
Microbes and Infection 2018Growing knowledge of the complexity of the host-pathogen interactions during the course of an infection revealed an amazing variability of bacterial pathogens within the... (Review)
Review
Growing knowledge of the complexity of the host-pathogen interactions during the course of an infection revealed an amazing variability of bacterial pathogens within the same host tissue site. This heterogeneity in bacterial populations is either the result of a different bacterial response to a slightly divergent tissue microenvironment or is caused by a genetic circuit in which small endogenous fluctuations in a small number of transcription factors drive gene expression in combination with a positive feedback loop. As a result host-pathogen encounters can have different outcomes in individual cells, which enables bet-hedging and/or a co-operative behavior that enhance bacterial fitness and virulence, drive different host responses and promote resistance of small subpopulations to antibiotic treatment. This has a strong impact on the progression and control of the infection, which must be considered for the development of successful antimicrobial therapies.
Topics: Adaptation, Physiological; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Genetic Fitness; Host-Pathogen Interactions; Phenotype; Virulence
PubMed: 29409898
DOI: 10.1016/j.micinf.2018.01.008 -
FEMS Microbiology Reviews Sep 2017Bacterial virulence is highly dynamic and context-dependent. For this reason, it is challenging to predict how molecular changes affect the growth of a pathogen in a... (Review)
Review
Bacterial virulence is highly dynamic and context-dependent. For this reason, it is challenging to predict how molecular changes affect the growth of a pathogen in a host and its spread in host population. Two schools of thought have taken quite different directions to decipher the underlying principles of bacterial virulence. While molecular infection biology is focusing on the basic mechanisms of the pathogen-host interaction, evolution biology takes virulence as one of several parameters affecting pathogen spread in a host population. We review both approaches and discuss how they can complement each other in order to obtain a comprehensive understanding of bacterial virulence, its emergence, maintenance and evolution.
Topics: Bacteria; Biological Evolution; Host-Pathogen Interactions; Virulence
PubMed: 28531298
DOI: 10.1093/femsre/fux023 -
Microbiology Spectrum Apr 2018Temperature variation is one of the multiple parameters a microbial pathogen encounters when it invades a warm-blooded host. To survive and thrive at host body... (Review)
Review
Temperature variation is one of the multiple parameters a microbial pathogen encounters when it invades a warm-blooded host. To survive and thrive at host body temperature, human pathogens have developed various strategies to sense and respond to their ambient temperature. An instantaneous response is mounted by RNA thermometers (RNATs), which are integral sensory structures in mRNAs that modulate translation efficiency. At low temperatures outside the host, the folded RNA blocks access of the ribosome to the translation initiation region. The temperature shift upon entering the host destabilizes the RNA structure and thus permits ribosome binding. This reversible zipper-like mechanism of RNATs is ideally suited to fine-tune virulence gene expression when the pathogen enters or exits the body of its host. This review summarizes our present knowledge on virulence-related RNATs and discusses recent developments in the field.
Topics: Bacteria; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; Immune Evasion; Iron; Nucleic Acid Conformation; Quorum Sensing; RNA, Bacterial; RNA, Messenger; Temperature; Virulence
PubMed: 29623874
DOI: 10.1128/microbiolspec.RWR-0012-2017 -
Frontiers in Cellular and Infection... 2019During infection, bacterial pathogens successfully sense, respond and adapt to a myriad of harsh environments presented by the mammalian host. This exquisite level of... (Review)
Review
During infection, bacterial pathogens successfully sense, respond and adapt to a myriad of harsh environments presented by the mammalian host. This exquisite level of adaptation requires a robust modulation of their physiological and metabolic features. Additionally, virulence determinants, which include host invasion, colonization and survival despite the host's immune responses and antimicrobial therapy, must be optimally orchestrated by the pathogen at all times during infection. This can only be achieved by tight coordination of gene expression. A large body of evidence implicate the prolific roles played by bacterial regulatory RNAs in mediating gene expression both at the transcriptional and post-transcriptional levels. This review describes mechanistic and regulatory aspects of bacterial regulatory RNAs and highlights how these molecules increase virulence efficiency in human pathogens. As illustrative examples, , the uropathogenic strain of , and have been selected.
Topics: Animals; Bacterial Infections; Bacterial Physiological Phenomena; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; RNA, Bacterial; Species Specificity; Virulence; Virulence Factors
PubMed: 31649894
DOI: 10.3389/fcimb.2019.00337 -
Current Opinion in Insect Science Aug 2016Bees are important pollinators of plants in both agricultural and non-agricultural landscapes. Recent losses of both managed and wild bee species have negative impacts... (Review)
Review
Bees are important pollinators of plants in both agricultural and non-agricultural landscapes. Recent losses of both managed and wild bee species have negative impacts on crop production and ecosystem diversity. Therefore, in order to mitigate bee losses, it is important to identify the factors most responsible. Multiple factors including pathogens, agrochemical exposure, lack of quality forage, and reduced habitat affect bee health. Pathogen prevalence is one factor that has been associated with colony losses. Numerous pathogens infect bees including fungi, protists, bacteria, and viruses, the majority of which are RNA viruses including several that infect multiple bee species. RNA viruses readily infect bees, yet there is limited understanding of their impacts on bee health, particularly in the context of other stressors. Herein we review the influence environmental factors have on the replication and pathogenicity of bee viruses and identify research areas that require further investigation.
Topics: Agriculture; Animals; Bees; Ecosystem; Virulence; Virus Physiological Phenomena; Virus Replication
PubMed: 27720045
DOI: 10.1016/j.cois.2016.04.009 -
Microbiology Spectrum Jun 2016Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit... (Review)
Review
Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit successful colonization are surprisingly varied and highlight remarkable metabolic flexibility. The constraints and immune pressures of distinct niches within the human body set the stage for understanding the mechanisms by which bacteria acquire critical nutrients. In this article we discuss how different bacterial pathogens carry out carbon and energy metabolism in the host and how they obtain or use key nutrients for replication and immune evasion.
Topics: Animals; Bacteria; Carbon; Energy Metabolism; Host-Pathogen Interactions; Humans; Immune Evasion; Metabolic Networks and Pathways; Virulence
PubMed: 27337445
DOI: 10.1128/microbiolspec.VMBF-0027-2015