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NPJ Biofilms and Microbiomes Mar 2024In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host.... (Review)
Review
In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host. The capsules, polymers that bacteria secrete near their cell wall, participates in numerous bacterial life processes and plays a crucial role in resisting host immune attacks and adapting to their niche. Here, we discuss the relationship between capsules and bacterial virulence, summarizing the molecular mechanisms of capsular regulation and pathogenesis to provide new insights into the research on the pathogenesis of pathogenic bacteria.
Topics: Bacterial Capsules; Virulence; Bacteria
PubMed: 38480745
DOI: 10.1038/s41522-024-00497-6 -
PLoS Pathogens Aug 2023Mycobacterium abscessus causes severe disease in patients with cystic fibrosis. Little is known in M. abscessus about the roles of small regulatory RNAs (sRNA) in gene...
Mycobacterium abscessus causes severe disease in patients with cystic fibrosis. Little is known in M. abscessus about the roles of small regulatory RNAs (sRNA) in gene regulation. We show that the sRNA B11 controls gene expression and virulence-associated phenotypes in this pathogen. B11 deletion from the smooth strain ATCC_19977 produced a rough strain, increased pro-inflammatory signaling and virulence in multiple infection models, and increased resistance to antibiotics. Examination of clinical isolate cohorts identified isolates with B11 mutations or reduced expression. We used RNAseq and proteomics to investigate the effects of B11 on gene expression and test the impact of mutations found in clinical isolates. Over 200 genes were differentially expressed in the deletion mutant. Strains with the clinical B11 mutations showed expression trends similar to the deletion mutant, suggesting partial loss of function. Among genes upregulated in the B11 mutant, there was a strong enrichment for genes with B11-complementary sequences in their predicted ribosome binding sites (RBS), consistent with B11 functioning as a negative regulator that represses translation via base-pairing to RBSs. Comparing the proteomes similarly revealed that upregulated proteins were strongly enriched for B11-complementary sequences. Intriguingly, genes upregulated in the absence of B11 included components of the ESX-4 secretion system, critical for M. abscessus virulence. Many of these genes had B11-complementary sequences at their RBSs, which we show is sufficient to mediate repression by B11 through direct binding. Altogether, our data show that B11 acts as a direct negative regulator and mediates (likely indirect) positive regulation with pleiotropic effects on gene expression and clinically important phenotypes in M. abscessus. The presence of hypomorphic B11 mutations in clinical strains is consistent with the idea that lower B11 activity may be advantageous for M. abscessus in some clinical contexts. This is the first report on an sRNA role in M. abscessus.
Topics: Mycobacterium abscessus; Virulence; Anti-Bacterial Agents; RNA, Small Untranslated
PubMed: 37603560
DOI: 10.1371/journal.ppat.1011575 -
BMC Plant Biology Feb 2024Pine wilt disease (PWD) is a devastating forest disease caused by the pinewood nematode (PWN), Bursaphelenchus xylophilus, a migratory endoparasite that infects several... (Review)
Review
Pine wilt disease (PWD) is a devastating forest disease caused by the pinewood nematode (PWN), Bursaphelenchus xylophilus, a migratory endoparasite that infects several coniferous species. During the last 20 years, advances have been made for understanding the molecular bases of PWN-host trees interactions. Major advances emerged from transcriptomic and genomic studies, which revealed some unique features related to PWN pathogenicity and constituted fundamental data that allowed the development of postgenomic studies. Here we review the proteomic approaches that were applied to study PWD and integrated the current knowledge on the molecular basis of the PWN pathogenicity. Proteomics has been useful for understanding cellular activities and protein functions involved in PWN-host trees interactions, shedding light into the mechanisms associated with PWN pathogenicity and being promising tools to better clarify host trees PWN resistance/susceptibility.
Topics: Animals; Proteomics; Virulence; Pinus; Plant Diseases; Tylenchida
PubMed: 38331735
DOI: 10.1186/s12870-024-04771-9 -
Virulence Dec 2023Nipah virus (NiV) is a high-risk pathogen which can cause fatal infections in humans. The Indian isolate from the 2018 outbreak in the Kerala state of India...
Nipah virus (NiV) is a high-risk pathogen which can cause fatal infections in humans. The Indian isolate from the 2018 outbreak in the Kerala state of India showed ~ 4% nucleotide and amino acid difference in comparison to the Bangladesh strains of NiV and the substitutions observed were mostly not present in the region of any functional significance except for the phosphoprotein gene. The differential expression of viral genes was observed following infection in Vero (ATCC® CCL-81™) and BHK-21 cells. Intraperitoneal infection in the 10-12-week-old, Syrian hamster model induced dose dependant multisystemic disease characterized by prominent vascular lesions in lungs, brain, kidney and extra vascular lesions in brain and lungs. Congestion, haemorrhages, inflammatory cell infiltration, thrombosis and rarely endothelial syncitial cell formation were seen in the blood vessels. Intranasal infection resulted in respiratory tract infection characterised by pneumonia. The model showed disease characteristics resembling the human NiV infection except that of myocarditis similar to that reported by NiV-Malaysia and NiV-Bangladesh isolates in hamster model. The variation observed in the genome of the Indian isolate at the amino acid levels should be explored further for any functional significance.
Topics: Cricetinae; Animals; Humans; Nipah Virus; Virulence; Henipavirus Infections; Mesocricetus; Genomics; Gene Expression Profiling
PubMed: 37312405
DOI: 10.1080/21505594.2023.2224642 -
Canadian Journal of Microbiology Jun 2024have a uniquely complex developmental life cycle that involves the coordination of morphological differentiation with the production of numerous bioactive specialized... (Review)
Review
have a uniquely complex developmental life cycle that involves the coordination of morphological differentiation with the production of numerous bioactive specialized metabolites. The majority of spp. are soil-dwelling saprophytes, while plant pathogenicity is a rare attribute among members of this genus Phytopathogenic are responsible for economically important diseases such as common scab, which affects potato and other root crops. Following the acquisition of genes encoding virulence factors, pathogens are expected to have specifically adapted their regulatory pathways to enable transition from a primarily saprophytic to a pathogenic lifestyle. Investigations of the regulation of pathogenesis have primarily focused on and the principal pathogenicity determinant thaxtomin A. The coordination of growth and thaxtomin A production in this species is controlled in a hierarchical manner by cluster-situated regulators, pleiotropic regulators, signalling and plant-derived molecules, and nutrients. Although the majority of phytopathogenic produce thaxtomins, many also produce additional virulence factors, and there are scab-causing pathogens that do not produce thaxtomins. The development of effective control strategies for common scab and other plant diseases requires a more in-depth understanding of the genetic and environmental factors that modulate the plant pathogenic lifestyle of these organisms.
Topics: Streptomyces; Plant Diseases; Virulence; Virulence Factors; Gene Expression Regulation, Bacterial; Bacterial Proteins; Plants; Solanum tuberosum; Indoles; Piperazines
PubMed: 38190652
DOI: 10.1139/cjm-2023-0171 -
Science Advances Sep 2023Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in...
Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5-infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity.
Topics: Animals; Mice; Virulence; COVID-19; SARS-CoV-2; Antiviral Agents; Mice, Transgenic
PubMed: 37738347
DOI: 10.1126/sciadv.adj1736 -
BMC Microbiology Aug 2023Vascular system is affected by diseases that can seriously damage plant health by inducing browning and death of branches. This study aimed to identify and analyze the...
BACKGROUND
Vascular system is affected by diseases that can seriously damage plant health by inducing browning and death of branches. This study aimed to identify and analyze the pathogenicity of Fusarium spp. isolates obtained from diseased peach branches in several peach-producing areas of China.
RESULTS
We obtained and confirmed nine Fusarium isolates based on morphological and molecular characteristics. Phylogenetic relationships using a combination of rDNA-internal transcribed spacer (ITS), elongation factor (EF)-1α, and mitochondrial small subunit (mtSSU) gene sequences were analyzed. GJH-Z1, GJH-6, and GJH-1 were identified as F. avenaceum; HYR-Z3, and ZLZT-6 as F. concentricum, HH-2020-G2, and HYTZ-4 as F. solani, GG-2020-1 as F. asiaticum, SYGZ-1 as F. equiseti. Through acupuncture comparison, the pathogenicity of F. equiseti (SYGZ-1) was highest amongst nine strains. Meanwhile, F. concentricum (HYR-Z3 and ZLZT-6), and F. solaini (HYTZ-4) had a higher level of pathogenicity as revealed by impregnation.
CONCLUSIONS
Our study shed light on the findings that Fusarium spp. can inflict vascular bundle browning of peach plants. Our results will extend the understanding of pathogenic diseases in China's peach industry.
Topics: Fusarium; Prunus persica; Phylogeny; Virulence; China
PubMed: 37550608
DOI: 10.1186/s12866-023-02958-y -
Current Opinion in Microbiology Jun 2024Bacterial pathogens can infect a wide range of hosts and pose a threat to public and animal health as well as to agriculture. The emergence of antibiotic-resistant... (Review)
Review
Bacterial pathogens can infect a wide range of hosts and pose a threat to public and animal health as well as to agriculture. The emergence of antibiotic-resistant strains has increased this risk by making the treatment of bacterial infections even more challenging. Pathogenic bacteria thrive in various ecological niches, but they can also be specifically targeted and killed by bacteriophages (phages). Lytic phages are now investigated and even used, in some cases, as alternatives or complements to antibiotics for preventing or treating bacterial infections (phage therapy). As such, it is key to identify factors responsible for phage specificity and efficiency. Here, we review recent advances in virulence-associated factors that are targeted by phages. We highlight components of the bacterial cell surface, effector systems, and motility structures exploited by phages and the effects of phages on cell aggregation and communication. We also look at the fitness trade-off of phage resistance.
Topics: Bacteriophages; Virulence Factors; Bacteria; Phage Therapy; Bacterial Infections; Animals; Humans; Virulence
PubMed: 38569419
DOI: 10.1016/j.mib.2024.102471 -
Virulence Dec 2023Clade 2.3.4.4 H5N6 avian influenza virus (AIV) has been predominant in poultry in China, and the circulating haemagglutinin (HA) gene has changed from clade 2.3.4.4h to...
Clade 2.3.4.4 H5N6 avian influenza virus (AIV) has been predominant in poultry in China, and the circulating haemagglutinin (HA) gene has changed from clade 2.3.4.4h to clade 2.3.4.4b in recent years. In 2021, we isolated four H5N6 viruses from ducks during the routine surveillance of AIV in China. The whole-genome sequencing results demonstrated that the four isolates all belonged to the currently prevalent clade 2.3.4.4b but had different internal gene constellations, which could be divided into G1 and G2 genotypes. Specifically, G1 possessed H9-like PB2 and PB1 genes on the H5-like genetic backbone while G2 owned an H3-like PB1 gene and the H5-like remaining internal genes. By determining the characteristics of H5N6 viruses, including growth performance on different cells, plaque-formation ability, virus attachment ability, and pathogenicity and transmission in different animal models, we found that G1 strains were more conducive to replication in mammalian cells (MDCK and A549) and BALB/c mice than G2 strains. However, G2 strains were more advantageously replicated in avian cells (CEF and DF-1) and slightly more transmissible in waterfowls (mallards) than G1 strains. This study enriched the epidemiological data of H5 subtype AIV to further understand its dynamic evolution, and laid the foundation for further research on the mechanism of low pathogenic AIV internal genes in generating novel H5 subtype reassortants.
Topics: Animals; Mice; Virulence; China; Ducks; Genotype; Influenza A virus; Mice, Inbred BALB C; Mammals
PubMed: 37635408
DOI: 10.1080/21505594.2023.2250065 -
Molecular Plant Pathology Sep 2023Phospholipase C (PLC) generates various second messenger molecules and mediates phospholipid hydrolysis. In recent years, the important roles of plant and fungal PLC in... (Review)
Review
Phospholipase C (PLC) generates various second messenger molecules and mediates phospholipid hydrolysis. In recent years, the important roles of plant and fungal PLC in disease resistance and pathogenicity, respectively, have been determined. However, the roles of PLC in plants and fungi are unintegrated and relevant literature is disorganized. This makes it difficult for researchers to implement PLC-based strategies to improve disease resistance in plants. In this comprehensive review, we summarize the structure, classification, and phylogeny of the PLCs involved in plant biotic stress resistance and fungal pathogenicity. PLCs can be divided into two groups, nonspecific PLC (NPC) and phosphatidylinositol-specific PLC (PI-PLC), which present marked differences in phylogenetic evolution. The products of PLC genes in fungi play significant roles in physiological activity and pathogenesis, whereas those encoded by plant PLC genes mediate the immune response to fungi. This review provides a perspective for the future control of plant fungal diseases.
Topics: Type C Phospholipases; Plant Proteins; Disease Resistance; Phylogeny; Virulence; Plants; Stress, Physiological
PubMed: 37119461
DOI: 10.1111/mpp.13343