Microbial Pathogenesis

For a pathogenic microbe to cause disease in a susceptible host, it must gain access to that host first. The pathogenicity of a microbe is determined by the virulence factors alongside other innate mechanisms. Apart from the initiation of infection, these virulence factors also enable the pathogenic microorganism to survive in the new environment within the susceptible host. They also enable the pathogenic microorganism to invade the host, colonize, and evade the host defense mechanisms. These virulence factors include; invasins, capsules, siderophores, adhesins, enzymes, endotoxins, and exotoxins. Key words: Pathogenicity factors and Pathological effect on cells.

Categorizing sequences of concern by function to better assess mechanisms of microbial pathogenesis

To identify sequences with a role in microbial pathogenesis, we assessed the adequacy of their annotation by existing controlled vocabularies and sequence databases. Our goal was to regularize descriptions of microbial pathogenesis for improved integration with bioinformatic applications. Here we review the challenges of annotating sequences for pathogenic activity. We relate the categorization of more than 2750 sequences of pathogenic microbes through a controlled vocabulary called Functions of Sequences of Concern (FunSoCs). These allow for an ease of description by both humans and machines. We provide a subset of 220 fully annotated sequences in the supplementary material as examples. The use of this compact (∼30 terms) controlled vocabulary has potential benefits for research in microbial genomics, public health, biosecurity, biosurveillance, and the characterization of new and emerging pathogens.

Macrophages in Microbial Pathogenesis: Commonalities of Defense Evasion Mechanisms

Macrophages are key arsenals of the immune system against invaders. After compartmental isolation of a pathogen in phagosomes, the host immune response attempts to neutralize the pathogen. However, pathogens possess the ability to subvert these assaults and can also convert macrophages into their replicative niche. The multiple host defense evasion mechanisms employed by these pathogens like phagosome maturation arrest, molecular mimicry through secretory antigens, interference with host signaling, active radical neutralization, inhibition of phagosome acidification, alteration of programmed cell death and many other mechanisms. Macrophage biology as a part of the host-pathogen interaction has expanded rapidly in the past decade. The present review aims to shed some light upon the macrophage defense evasion strategies employed by infecting pathogens. We have also incorporated recent knowledge in the field of macrophage dynamics during infection and evolutionary perspectives of macrophage dynamics.

Functions of Sphingolipids in Pathogenesis During Host–Pathogen Interactions

Sphingolipids are a class of membrane lipids that serve as vital structural and signaling bioactive molecules in organisms ranging from yeast to animals. Recent studies have emphasized the importance of sphingolipids as signaling molecules in the development and pathogenicity of microbial pathogens including bacteria, fungi, and viruses. In particular, sphingolipids play key roles in regulating the delicate balance between microbes and hosts during microbial pathogenesis. Some pathogens, such as bacteria and viruses, harness host sphingolipids to promote development and infection, whereas sphingolipids from both the host and pathogen are involved in fungus–host interactions. Moreover, a regulatory role for sphingolipids has been described, but their effects on host physiology and metabolism remain to be elucidated. Here, we summarize the current state of knowledge about the roles of sphingolipids in pathogenesis and interactions with host factors, including how sphingolipids modify pathogen and host metabolism with a focus on pathogenesis regulators and relevant metabolic enzymes. In addition, we discuss emerging perspectives on targeting sphingolipids that function in host–microbe interactions as new therapeutic strategies for infectious diseases.

Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis

In eukaryotic organisms, transfer RNA (tRNA)-derived fragments have diverse biological functions. Considering the conserved sequences of tRNAs, it is not surprising that endogenous tRNA fragments in bacteria also play important regulatory roles. Recent studies have shown that microbes secrete extracellular vesicles (EVs) containing tRNA fragments and that the EVs deliver tRNA fragments to eukaryotic hosts where they regulate gene expression. Here, we review the literature describing microbial tRNA fragment biogenesis and how the fragments secreted in microbial EVs suppress the host immune response, thereby facilitating chronic infection. Also, we discuss knowledge gaps and research challenges for understanding the pathogenic roles of microbial tRNA fragments in regulating the host response to infection.

SeqScreen: Accurate and Sensitive Functional Screening of Pathogenic Sequences via Ensemble Learning

Modern benchtop DNA synthesis techniques and increased concern of emerging pathogens have elevated the importance of screening oligonucleotides for pathogens of concern. However, accurate and sensitive characterization of oligonucleotides is an open challenge for many of the current techniques and ontology-based tools. To address this gap, we have developed a novel software tool, SeqScreen, that can accurately and sensitively characterize short DNA sequences using a set of curated Functions of Sequences of Concern (FunSoCs), novel functional labels specific to microbial pathogenesis which describe the pathogenic potential of individual proteins. We show that our ensemble machine learning model after training on these curations can label sequences with FunSoCs via an imbalanced multi-class and multi-label classification task with high accuracy. In summary, SeqScreen represents a first step towards a novel paradigm of functionally informed pathogen characterization from genomic and metagenomic datasets. SeqScreen is open-source and freely available for download at: https://www.gitlab.com/treangenlab/seqscreen .

Microbial Pathogenesis and Pathophysiology of Alzheimer's Disease: A Systematic Assessment of Microorganisms' Implications in the Neurodegenerative Disease

Microbial infections have been linked to the pathogenesis and pathophysiology of Alzheimer's disease (AD) and other neurodegenerative diseases. The present study aimed to synthesise and assess global evidence of microbial pathogenesis and pathophysiology in AD (MPP-AD) and associated neurodegenerative conditions using integrated science mapping and content analytics to explore the associated research landscape. Relevant MPP-AD documents were retrieved from Web of Science and Scopus according to PRISMA principles and analysed for productivity/trend linked to authors/countries, thematic conceptual framework, and international collaborative networks. A total of 258 documents published from 136 sources to 39.42 average citations/document were obtained on MPP-AD. The co-authors per document were 7.6, and the collaboration index was 5.71. The annual research outputs increased tremendously in the last 6 years from 2014 to 2019, accounting for 66% compared with records in the early years from 1982 to 1990 (16%). The USA (n = 71, freq. = 30.34%), United Kingdom (n = 32, freq. = 13.68%) and China (n = 27, 11.54%) ranked in first three positions in term of country's productivity. Four major international collaboration clusters were found in MPP-AD research. The country collaboration network in MPP-AD was characteristic of sparse interaction and acquaintanceship (density = 0.11, diameter = 4). Overall, international collaboration is globally inadequate [centralisation statistics: degree (40.5%), closeness (4%), betweenness (23%), and eigenvector (76.7%)] against the robust authors' collaboration index of 5.71 in MPP-AD research. Furthermore, four conceptual thematic frameworks (CTF) namely, CTF#1, roles of microbial/microbiome infection and dysbiosis in cognitive dysfunctions; CTF#2, bacterial infection specific roles in dementia; CTF#3, the use of yeast as a model system for studying MPP-AD and remediation therapy; and CFT#4, flow cytometry elucidation of amyloid-beta and aggregation in Saccharomyces cerevisiae model. Finally, aetiology-based mechanisms of MPP-AD, namely, gut microbiota, bacterial infection, and viral infection, were comprehensively discussed. This study provides an overview of MPP-AD and serves as a stepping stone for future preparedness in MPP-AD-related research.