-
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 -
Microbiology Spectrum Aug 2022Acinetobacter baumannii, one of the most successful bacteria causing severe nosocomial infection, was identified as a top-priority pathogen by the WHO. Thus, genetic...
Acinetobacter baumannii, one of the most successful bacteria causing severe nosocomial infection, was identified as a top-priority pathogen by the WHO. Thus, genetic manipulations to clarify the potential targets for fighting A. baumannii resistance and virulence are vital. Polyphosphate (polyP) kinase (PPK) is conserved in nearly all bacteria and is responsible for polyP formation, which is associated with bacterial pathogenicity and antibiotic resistance. In this study, -deficient (Δ::Apr), -complemented (Δ::Apr/PJL02-), and wild-type strains of A. baumannii ATCC 17978 were used to determine the influence of PPK1 on A. baumannii virulence and persistence mainly by polyP quantification, surface motility, biofilm formation, and bacterial persistence assays. Our work found that PPK1 is indispensable for polyP formation and that the motility of the PPK1-deficient strain was significantly impaired due to the lack of a pilus-like structure typically present compared with the complemented and wild-type strains. The deficiency of PPK1 also inhibited the biofilm formation of A. baumannii and decreased bacterial persistence under stimuli of high-concentration ampicillin (Amp) treatment, HO stress, heat shock, and starvation stress. Furthermore, -deficient bacterium-infected mice showed a significantly reduced bacterial load and a decreased inflammatory response. However, complementation with PPK1 effectively rescued the impaired virulence and persistence of -deficient A. baumannii. In addition, metabonomic analysis revealed that PPK1 was associated with glycerophospholipid metabolism and fatty acid biosynthesis. Taken together, our results suggest that targeting PPK1 to control A. baumannii pathogenicity and persistence is a feasible strategy to fight this pathogen. A. baumannii was identified as a top-priority pathogen by the WHO due to its antibiotic resistance. Meanwhile, the pathogenicity of A. baumannii mediated by several vital virulence factors also cannot be ignored. Here, the role of PPK1 in A. baumannii was also explored. We found that the motility ability and biofilm formation of a PPK1-deficient strain were significantly impaired. Furthermore, PPK1 was essential for its persistence maintenance to resist stimuli of high-concentration Amp treatment, HO stress, heat shock, and starvation stress. Metabonomic analysis revealed that PPK1 was associated with glycerophospholipid metabolism and fatty acid biosynthesis. In addition, -deficient bacterium-infected mice showed significantly reduced bacterial loads and a decreased inflammatory responses . Together, our results suggest that PPK1 is vital for A. baumannii pathogenicity and persistence.
Topics: Acinetobacter baumannii; Adenosine Monophosphate; Animals; Biofilms; Fatty Acids; Glycerophospholipids; Hydrogen Peroxide; Mice; Phosphotransferases (Phosphate Group Acceptor); Virulence
PubMed: 35867473
DOI: 10.1128/spectrum.01230-22 -
Frontiers in Cellular and Infection... 2021The mammalian gut microbial community, known as the gut microbiota, comprises trillions of bacteria, which co-evolved with the host and has an important role in a... (Review)
Review
The mammalian gut microbial community, known as the gut microbiota, comprises trillions of bacteria, which co-evolved with the host and has an important role in a variety of host functions that include nutrient acquisition, metabolism, and immunity development, and more importantly, it plays a critical role in the protection of the host from enteric infections associated with exogenous pathogens or indigenous pathobiont outgrowth that may result from healthy gut microbial community disruption. Microbiota evolves complex mechanisms to restrain pathogen growth, which included nutrient competition, competitive metabolic interactions, niche exclusion, and induction of host immune response, which are collectively termed colonization resistance. On the other hand, pathogens have also developed counterstrategies to expand their population and enhance their virulence to cope with the gut microbiota colonization resistance and cause infection. This review summarizes the available literature on the complex relationship occurring between the intestinal microbiota and enteric pathogens, describing how the gut microbiota can mediate colonization resistance against bacterial enteric infections and how bacterial enteropathogens can overcome this resistance as well as how the understanding of this complex interaction can inform future therapies against infectious diseases.
Topics: Animals; Bacteria; Bacterial Infections; Gastrointestinal Microbiome; Virulence
PubMed: 35004340
DOI: 10.3389/fcimb.2021.716299 -
Trends in Microbiology May 2020Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into... (Review)
Review
Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into the regulatory network of the cell and are often controlled by pre-existing transcription factors. In this review, we highlight recent advances that have been made in characterizing this regulatory flexibility in prominent members of the Enterobacteriaceae. We focus on the direct global interactions between transcription factors and their target genes in pathogenic Escherichia coli and Salmonella revealed using chromatin immunoprecipitation coupled with next-generation sequencing. Furthermore, the implications and advantages of such regulatory adaptations in benefiting distinct pathogenic lifestyles are discussed.
Topics: Chromatin Immunoprecipitation; Escherichia coli; Escherichia coli Infections; Gene Expression Regulation, Bacterial; High-Throughput Nucleotide Sequencing; Salmonella; Salmonella Infections; Transcription Factors; Transcription, Genetic; Virulence
PubMed: 32298614
DOI: 10.1016/j.tim.2020.01.002 -
International Journal of Molecular... Feb 2023The growth-defense trade-off in plants is a phenomenon whereby plants must balance the allocation of their resources between developmental growth and defense against... (Review)
Review
The growth-defense trade-off in plants is a phenomenon whereby plants must balance the allocation of their resources between developmental growth and defense against attack by pests and pathogens. Consequently, there are a series of points where growth signaling can negatively regulate defenses and where defense signaling can inhibit growth. Light perception by various photoreceptors has a major role in the control of growth and thus many points where it can influence defense. Plant pathogens secrete effector proteins to manipulate defense signaling in their hosts. Evidence is emerging that some of these effectors target light signaling pathways. Several effectors from different kingdoms of life have converged on key chloroplast processes to take advantage of regulatory crosstalk. Moreover, plant pathogens also perceive and react to light in complex ways to regulate their own growth, development, and virulence. Recent work has shown that varying light wavelengths may provide a novel way of controlling or preventing disease outbreaks in plants.
Topics: Plants; Light Signal Transduction; Signal Transduction; Virulence; Chloroplasts; Plant Diseases; Plant Immunity
PubMed: 36835216
DOI: 10.3390/ijms24043803 -
PeerJ 2022Pathogen accumulation after introduction is unavoidable for exotic plants over a long period of time. Therefore, it is important to understand whether plant invasion...
Pathogen accumulation after introduction is unavoidable for exotic plants over a long period of time. Therefore, it is important to understand whether plant invasion promotes novel pathogen emergence and increases the risk of pathogen movement among agricultural, horticultural, and wild native plants. In this study, we used multiple gene analysis to characterize the species composition of 104 isolates of obtained from the invasive plant and native plants from Yunnan, Hubei, Guizhou, Sichuan, and Guangxi in China. Phylogenetically, these strains were from (88.5%), (10.6%) and (0.9%). There was a high amount of sharing between strains associated with and with local plants. Pathogenicity tests indicated that most of these strains are generalists; the isolates with a wider host range were more virulent to the plant. Woody plants were more resistant to these strains than herbaceous plants and vines. However, the invasive plant was highly sensitive to these strains. Our data are valuable for understanding how invasion impacts the species composition of the native plant and whether invasion causes potential disease risks in invaded ecosystems.
Topics: Ageratina; Alternaria; Ecosystem; Introduced Species; Virulence; China; Plants
PubMed: 35251785
DOI: 10.7717/peerj.13012 -
Journal of Virology Jul 2023Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript,...
Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript, we report the generation of a reverse genetics system C(RGS) for the highly virulent US PEDV strain Minnesota (PEDV-MN; GenBank accession number KF468752), which was based on the assembly and cloning of synthetic DNA, using vaccinia virus as a cloning vector. Viral rescue was only possible following the substitution of 2 nucleotides within the 5'UTR and 2 additional nucleotides within the spike gene, based on the sequence of the cell culture-adapted strains. Besides displaying a highly pathogenic phenotype in newborn piglets, in comparison with the parental virus, the rescued recombinant PEDV-MN was used to confirm that the PEDV spike gene has an important role in PEDV virulence and that the impact of an intact PEDV ORF3 on viral pathogenicity is modest. Moreover, a chimeric virus with a TGEV spike gene in the PEDV backbone generated with RGS was able to replicate efficiently and could be readily transmitted between piglets. Although this chimeric virus did not cause severe disease upon the initial infection of piglets, there was evidence of increasing pathogenicity upon transmission to contact piglets. The RGS described in this study constitutes a powerful tool with which to study PEDV pathogenesis and can be used to generate vaccines against porcine enteric coronaviruses. PEDV is a swine pathogen that is responsible for significant animal and economic losses worldwide. Highly pathogenic variants can lead to a mortality rate of up to 100% in newborn piglets. The generation of a reverse genetics system for a highly virulent PEDV strain originating from the United States is an important step in phenotypically characterizing PEDV. The synthetic PEDV mirrored the authentic isolate and displayed a highly pathogenic phenotype in newborn piglets. With this system, it was possible to characterize potential viral virulence factors. Our data revealed that an accessory gene (ORF3) has a limited impact on pathogenicity. However, as it is also now known for many coronaviruses, the PEDV spike gene is one of the main determinants of pathogenicity. Finally, we show that the spike gene of another porcine coronavirus, namely, TGEV, can be accommodated in the PEDV genome background, suggesting that similar viruses can emerge in the field via recombination.
Topics: Animals; United States; Swine; Virulence; Porcine epidemic diarrhea virus; Spike Glycoprotein, Coronavirus; Swine Diseases; Reverse Genetics; Coronavirus Infections; Nucleotides; Diarrhea
PubMed: 37358450
DOI: 10.1128/jvi.01964-22 -
Microbiology Spectrum Feb 2023Verticillium dahliae Kleb is a typical soilborne pathogen that can cause vascular wilt disease on more than 400 plants. Functional analysis of genes related to the...
Verticillium dahliae Kleb is a typical soilborne pathogen that can cause vascular wilt disease on more than 400 plants. Functional analysis of genes related to the growth and virulence is crucial to revealing the molecular mechanism of the pathogenicity of V. dahliae. Glycosidase hydrolases can hydrolyze the glycosidic bond, and some can cause host plant immune response to V. dahliae. Here, we reported a functional validation of VdGAL4 as an α-galactosidase that belongs to glycoside hydrolase family 27. VdGAL4 could cause plant cell death, and its signal peptide plays an important role in cellular immune response. VdGAL4-triggered cell death depends on BAK1 and SOBIR1 in Nicotiana benthamiana. In V. dahliae, the function of in mycelial growth, conidia, microsclerotium, and pathogenicity was studied by constructing deletion and complementation mutants. Results showed that the deletion of reduced the conidial yield and conidial germination rate of V. dahliae and changed the microscopic morphology of conidia; the mycelia were arranged more disorderly and were unable to produce microsclerotium. The deletion mutants exhibited reduced utilization of different carbon sources, such as raffinose and sucrose. The deletion mutants were also more sensitive to abiotic stress agents of SDS, sorbitol, low-temperature stress of 16°C, and high-temperature stress of 45°C. In addition, the deletion mutants lost the ability to penetrate cellophane and its mycelium were disorderly arranged. Remarkably, deletion mutants exhibited reduced pathogenicity of V. dahliae. These results showed that played a critical role in the pathogenicity of V. dahliae by regulating mycelial growth, conidial morphology, and the formation of microsclerotium. This study showed that α-galactosidase of V. dahliae could activate plant immune response and plays an important role in conidial morphology and yield, formation of microsclerotia, and mycelial penetration. deletion mutants significantly reduced the pathogenicity of V. dahliae. These findings deepened the understanding of pathogenic virulence factors and how the mechanism of pathogenic fungi infected the host, which may help to seek new strategies for effective control of plant diseases caused by pathogenic fungi.
Topics: Virulence; alpha-Galactosidase; Verticillium; Virulence Factors; Ascomycota; Plants; Plant Diseases; Fungal Proteins
PubMed: 36475739
DOI: 10.1128/spectrum.03515-22 -
Virulence Dec 2021is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional...
is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional ability to adapt to stress conditions encountered in different environments, resulting in a ubiquitous distribution. Because some food preservation methods and disinfection protocols in food-processing environments cannot efficiently prevent contaminations, constitutes a threat to human health and a challenge to food safety. In the host, colonizes the gastrointestinal tract, crosses the intestinal barrier, and disseminates through the blood to target organs. In immunocompromised individuals, the elderly, and pregnant women, the pathogen can cross the blood-brain and placental barriers, leading to neurolisteriosis and materno-fetal listeriosis. Molecular and cell biology studies of infection have proven to be a versatile pathogen that deploys unique strategies to invade different cell types, survive and move inside the eukaryotic host cell, and spread from cell to cell. Here, we present the multifaceted life cycle from a comprehensive perspective. We discuss genetic features of pathogenic species, analyze factors involved in food contamination, and review bacterial strategies to tolerate stresses encountered both during food processing and along the host's gastrointestinal tract. Then we dissect host-pathogen interactions underlying listerial pathogenesis in mammals from a cell biology and systemic point of view. Finally, we summarize the epidemiology, pathophysiology, and clinical features of listeriosis in humans and animals. This work aims to gather information from different fields crucial for a comprehensive understanding of the pathogenesis of
Topics: Adaptation, Physiological; Aged; Animals; Female; Humans; Listeria monocytogenes; Listeriosis; Mammals; Placenta; Pregnancy; Virulence
PubMed: 34612177
DOI: 10.1080/21505594.2021.1975526 -
Gene May 2024Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted...
Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted effector that induces necrotic lesions in plants. It interacts with host receptor-like kinases and inhibits their kinase activity. FsNis1 contains the Nis1 structure and triggered a pathogen-associated molecular pattern-triggered immune response in Nicotiana benthamiana, as reflected by causing reactive oxygen species production, callose accumulation, and the upregulated expression of defense response genes. Knockout of this gene in F. sacchari revealed a significant reduction in its pathogenicity, whereas the pathogenicity of the complementary mutant recovered to the wild-type levels, making this gene an important virulence factor for F. sacchari. In addition, the signal peptide of FsNis1 was required for the induction of cell death and PTI response in N. benthamiana. Thus, FsNis1 may not only be a key virulence factor for F. sacchari but may also induce defense responses in plants. These findings provide new insights into the function of Nis1 in host-pathogen interactions.
Topics: Fusarium; Plant Immunity; Virulence; Virulence Factors; Plant Diseases
PubMed: 38342252
DOI: 10.1016/j.gene.2024.148260