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Nucleic Acids Research Jan 2015Pathogenicity is a complex multifactorial process confounded by the concerted activity of genetic regions associated with virulence and/or resistance determinants....
Pathogenicity is a complex multifactorial process confounded by the concerted activity of genetic regions associated with virulence and/or resistance determinants. Pathogenicity islands (PAIs) and resistance islands (REIs) are key to the evolution of pathogens and appear to play complimentary roles in the process of bacterial infection. While PAIs promote disease development, REIs give a fitness advantage to the host against multiple antimicrobial agents. The Pathogenicity Island Database (PAIDB, http://www.paidb.re.kr) has been the only database dedicated to providing comprehensive information on all reported PAIs and candidate PAIs in prokaryotic genomes. In this study, we present PAIDB v2.0, whose functionality is extended to incorporate REIs. PAIDB v2.0 contains 223 types of PAIs with 1331 accessions, and 88 types of REIs with 108 accessions. With an improved detection scheme, 2673 prokaryotic genomes were analyzed to locate candidate PAIs and REIs. With additional quantitative and qualitative advancements in database content and detection accuracy, PAIDB will continue to facilitate pathogenomic studies of both pathogenic and non-pathogenic organisms.
Topics: Databases, Nucleic Acid; Drug Resistance, Microbial; Genome, Microbial; Genomic Islands; Internet; Virulence
PubMed: 25336619
DOI: 10.1093/nar/gku985 -
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 -
Microbiology and Molecular Biology... Jun 1997Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their... (Review)
Review
Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics.
Topics: Bacteria; Bacterial Adhesion; Bacterial Infections; Bacterial Toxins; Gene Expression Regulation, Bacterial; Phagocytes; Virulence
PubMed: 9184008
DOI: 10.1128/mmbr.61.2.136-169.1997 -
Genes Jul 2021RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to... (Review)
Review
RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.
Topics: Bacteria; Host Adaptation; Host-Pathogen Interactions; RNA Processing, Post-Transcriptional; RNA, Bacterial; Virulence
PubMed: 34440299
DOI: 10.3390/genes12081125 -
Biomolecules Jun 2021Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small... (Review)
Review
Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections. In the current review, strategies to design vaccines against selected pathogens are presented and connected to the biology of the system. The examples are given for , , , , and other human pathogens, and discussed in terms of effectiveness and long-term protection.
Topics: Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Secretion Systems; Bacterial Vaccines; Humans; Virulence
PubMed: 34203937
DOI: 10.3390/biom11060892 -
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 -
Frontiers in Cellular and Infection... 2022is a zoonotic pathogen that can cause fatal disease in patients who are immunocompromised. At present, the epidemiology and pathogenic mechanisms of infection are not...
is a zoonotic pathogen that can cause fatal disease in patients who are immunocompromised. At present, the epidemiology and pathogenic mechanisms of infection are not clear. This study characterized the genomes of 53 strains from different sources. Pan-genome analysis showed that all strains contained 11481 pan genes, including 3690 core genes and 602 ~ 1079 accessory genes. Functional annotation of pan genome focused on the genes related to basic lifestyle, such as the storage and expression of metabolic and genetic information. Phylogenetic analysis based on pan-genome showed that the strains were clustered into six clades, which was not directly related to the isolation location and host source. Also, a total of 84 virulence genes were predicted in 53 strains. These virulence factors can be divided into 20 categories related to substance metabolism, secreted protein and immune escape. Meanwhile, six antibiotic resistance genes ( and ) were detected, and all strains carried related to rifamycin resistance. In addition, 28 plasmids were found in the 53 strains, belonging to Type-A (n = 14), Type-B (n = 8) and Type-N (n = 6), respectively. The genetic structures of the same type of plasmid were highly similar. In conclusion, strains show different genomic characteristics, virulence-related genes, potential drug resistance and virulence plasmid structures, which may be conducive to the evolution of its pathogenesis.
Topics: Humans; Phylogeny; Plasmids; Rhodococcus equi; Rifamycins; Virulence
PubMed: 35252029
DOI: 10.3389/fcimb.2022.807610 -
The ISME Journal Aug 2016Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and... (Review)
Review
Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and natural ecosystems. Most pathogens are likely to host parasites of their own, that is, hyperparasites, but how nested chains of parasites impact on disease dynamics is grossly neglected in the ecological and evolutionary literature. In this minireview we argue that the diversity and dynamics of micro-hyperparasites are an important component of natural host-pathogen systems. We use the current literature from a handful of key systems to show that observed patterns of pathogen virulence and disease dynamics may well be influenced by hyperparasites. Exploring these factors will shed light on many aspects of microbial ecology and disease biology, including resistance-virulence evolution, apparent competition, epidemiology and ecosystem stability. Considering the importance of hyperparasites in natural populations will have applied consequences for the field of biological control and therapeutic science, where hyperparastism is employed as a control mechanism but not necessarily ecologically understood.
Topics: Animals; Biological Evolution; Ecology; Ecosystem; Host-Pathogen Interactions; Humans; Parasites; Virulence
PubMed: 26784356
DOI: 10.1038/ismej.2015.247 -
BMC Veterinary Research Jul 2022Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida...
BACKGROUND
Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida serogroups A and D, and the knowledge about the serogroup F is limited. In the present study, a P. multocida serogroup F isolate designated s4 was recovered from the lungs of rabbits died of respiratory disease in Fujian, in the southeast of China. The pathogenicity and genomic features of the s4 were then determined.
RESULTS
The serotype and sequence type of s4 were F:L3 and ST12, respectively. The s4 was pathogenic for rabbits, but it was a low virulent strain comparing to the previously reported highly pathogenic P. multocida serogroup F strains J-4103, C21724H3km7, P-4218 and HN07. The whole genome of the s4 was then sequenced to understand the genomic basis for pathogenicity. Particularly, a large-sized fragment of approximate 275 kb in length was truncated from the chromosome to form a plasmid. Moreover, the in-frame deletion of natC and N-terminal redundance of gatF would resulted in the production of a mutant L3 outer core structure that was distinct from those of the other P. multocida strains belonging to the lipopolysaccharide genotype L3. We deduced that these features detected in the genome of s4 might impair the pathogenicity of the bacterium.
CONCLUSIONS
This study evaluated the pathogenicity and determined the genomic features of the rabbit sourced P. multocida serogroup F isolate s4, the observations and findings would helpful for the understanding of the pathogenicity variability and genetic diversity of P. multocida.
Topics: Animals; Genomics; Pasteurella Infections; Pasteurella multocida; Rabbits; Serogroup; Virulence
PubMed: 35869529
DOI: 10.1186/s12917-022-03381-7 -
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