Reactivation of hepatitis B virus infection - an important aspect of multifaceted problem.

In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the problem of occult hepatitis B virus (HBV) infection, that is a result of previous hepatitis B (PHB) and a source for reactivation of HBV. The prevalence of PHB is underestimated due to the lack of population testing programs. However, this condition not only complicate anticancer treatment, but may be responsible for the development of other diseases, like cancer or autoimmune disorders. Here we unveil possible mechanisms responsible for realization of these processes and suggest practical approaches for diagnosis and treatment.

HELICOBACTER PYLORI AND GALLBLADDER PATHOLOGIES: IS THERE A CAUSE-AND-EFFECT RELATIONSHIP?

The relationship between Helicobacter pylori infection and gallbladder diseases, particularly cholecystitis and gallbladder polyps, remains unclear. This study aimed to investigate the presence of H. pylori in gallbladder tissues and its potential role in gallbladder pathologies, as well as to examine the expression of chemokines CXCL2 and CXCL5 in these conditions. MATERIAL AND METHODS: A total of 137 laparoscopically excised gallbladders were analysed through histological examination, PCR for H. pylori-specific DNA, and quantitative real-time PCR for CXCL2 and CXCL5 gene expression. The study cohort included patients with acute calculous cholecystitis, chronic calculous cholecystitis, and gallbladder polyps. RESULTS: H. pylori was detected in 30.7% of cases by histological methods and 42.3% by PCR. Elevated expression of CXCL2 and CXCL5 was observed in 62% and 57.7% of cases, respectively, with a higher prevalence in acute cholecystitis compared to chronic conditions. However, no statistically significant association was found between H. pylori presence and the forms of cholecystitis, as well as between H. pylori presence and chemokine expression in gallbladder. CONCLUSIONS: The study did not establish a direct link between the presence of H. pylori infection and forms of gallbladder pathologies. The findings suggest that other factors other than H. pylori may contribute to the upregulation of CXCL2 and CXCL5 in gallbladder diseases. Further research is needed to elucidate the complex interactions between H. pylori, chemokines, and gallbladder pathologies.

Tuber pathogenicity of Macrophomina phaseolina strain 3 a isolated from rotten cassava tuber from farm lands in Osogbo, Osun State, Nigeria, its virulence genes and ADMET properties.

BACKGROUND: Macrophomina phaseolina is a pathogen that causes an opportunistic disease that spreads by soil and seeds and affects more than 500 different plant species, like fruits, trees, and row crops. Mycotoxins, such as phaseolinic acid, and phaseolinone, are produced by M. phaseolina isolates in previous investigations; however, the production of these mycotoxins seems to vary depending on the host and the region. METHODS AND RESULTS: In this study, Macrophomina phaseolina strain 3 A was isolated from rotten cassava tuber and identified using the analysis of the sequences of the internal transcribed spacer region. The isolate was inoculated on a fresh healthy cassava tuber at 25 °C and tuber-rotting potential was monitored for 4 weeks. Virulence genes MPH_06603, MPH_06955, and MPH_01521 were determined with designed primers, and secondary metabolites were characterized by FTIR and GCMS. The rotten tuber effect was observed from the 2nd week of the experiment with severe tuber rot and weight reduction. The PCR showed the presence of MPH_06603 virulence gene. The GCMS showed N-Methylpivalamide (115.0 m/z), Butane, 1,4-dimethoxy- (119.0 m/z), and 5-Hydroxymethylfurfural (126.0 m/z) were the predominant metabolites produced by the pathogen. The compounds in the metabolites inhibit CYP3A4 enzymes, cause eye irritation, and Human Ether-a-go-go-related gene inhibition. CONCLUSION: This study revealed that M. phaseolina was responsible for the cassava tuber rot which leads to a lower yield of farm produce. The metabolites produced are toxic and unsafe for human consumption. It is suggested that farmers should destroy any cassava affected by this pathogen to prevent its toxic effects on humans and animals.

Comprehensive blueprint of Salmonella genomic plasticity identifies hotspots for pathogenicity genes.

Understanding the dynamic evolution of Salmonella is vital for effective bacterial infection management. This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of Salmonella lineages. Through comprehensive genomic analysis of 12,244 Salmonella spp. genomes covering 2 species, 6 subspecies, and 46 serovars, we uncover distinct integration patterns of pathogenicity-related gene clusters into RGP, challenging traditional views of gene distribution. These RGP exhibit distinct preferences for specific genomic spots, and the presence or absence of such spots across Salmonella lineages profoundly shapes strain pathogenicity. RGP preferences are guided by conserved flanking genes surrounding integration spots, implicating their involvement in regulatory networks and functional synergies with integrated gene clusters. Additionally, we emphasise the multifaceted contributions of plasmids and prophages to the pathogenicity of diverse Salmonella lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of Salmonella. This unique insight identifies genomic spots in nonpathogenic lineages that hold the potential for harbouring pathogenicity genes, providing a foundation for predicting future adaptations and developing targeted strategies against emerging human pathogenic strains.

Epitranscriptomic m5C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection.

While the significance of N6-methyladenosine (m6A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m5C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m5C is more abundant than m6A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m5C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m5C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m5C-MeRIP-seq identified the NSUN2-dependent m5C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m5C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m5C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m5C methylation to SARS-CoV-2 RNA.

A time series transcriptome profiling of host cell responses to Newcastle disease virus infection.

Newcastle disease virus (NDV), an avian paramyxovirus, causes major economic losses in the poultry industry worldwide. NDV strains are classified as avirulent, moderately virulent, or virulent according to the severity of the disease they cause. In order to gain a deeper understanding of the molecular mechanisms of virus-host interactions, we conducted Illumina HiSeq-based RNA-Seq analysis on chicken embryo fibroblast (DF1) cells during the first 24 hours of infection with NDV strain Komarov. Comparative analysis of uninfected DF1 cells versus NDV-infected DF1 cells at 6, 12, and 24 h postinfection identified 462, 459, and 410 differentially expressed genes, respectively. The findings revealed an increase in the expression of genes linked to the MAPK signalling pathway in the initial stages of NDV infection. This overexpression potentially aids viral multiplication while hindering pathogen detection and subsequent immune responses from the host. Our findings provide initial insights into the early responses of DF1 cells to NDV infection.

Introduction.

The coronavirus disease 2019 (COVID-19) pandemic emerged just months after the publication of the first ever textbook devoted to cytokine storm syndromes (CSSs). The severe disease caused by COVID-19 and the intersection between immune responses and their pathologies played out before the world in media reports, in scientific publications, and through the personal narratives of millions of people's experiences. An entirely new immune-mediated disease, multisystem inflammatory disease in children (MISC), was described. Cytokines played a role in all of these areas, bringing the idea of a cytokine storm squarely to the front and center of the public eye. At the same time, science continued to progress in the lab and in the clinic, thus illuminating our understanding of CSSs both old and new since the publication of the first edition of this book. It was clear that a new edition was needed to keep up with these changes.

Infectious Triggers of Cytokine Storm Syndromes: Herpes Virus Family (Non-EBV).

The herpesviruses are the most common infectious agents associated with both primary and secondary cytokine storm syndromes (CSS). While Epstein-Barr Virus (EBV) is most frequently reported in association with CSS, cytomegalovirus (CMV) and many other herpesviruses (e.g., herpes simplex virus, varicella zoster virus, and human herpesviruses 6 and 8) are clearly associated with CSS in children and adults. Immunocompromised hosts, whether due to primary immunodeficiency or secondary immune compromise (e.g., solid organ or stem cell transplantation), appear to be at particularly increased risk of herpesvirus-associated CSS. In this chapter, the association of the non-EBV herpesviruses with CSS will be discussed, including predisposing factors and treatment considerations.

COVID-19-Related Multi-systemic Inflammatory Syndrome in Children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in children. This syndrome manifests about a month after the initial viral infection and is characterized by fever, multiorgan dysfunction, and systemic inflammation. This chapter will review the emergence, epidemiology, clinical characteristics, diagnosis, pathophysiology, immunomodulatory treatment, prognosis, outcomes, and prevention of MIS-C. While the pathophysiology of MIS-C remains to be defined, it is a post-infection, hyperinflammatory syndrome of childhood with elevated inflammatory cytokines.

Ecology and evolution of avian influenza viruses.

Four types of influenza virus have been identified in nature: influenza A, B, and C viruses are capable of infecting humans, and influenzas A and B cause annual epidemics (seasonal flu) in humans; however, influenza D is currently known to infect only pigs and cattle. The influenza A viruses (IAVs) are of greatest importance to humans, causing widespread significant morbidity and mortality, and have been responsible for at least five pandemics documented since the beginning of the 20th century (Table 1). The H1N1 and H3N2 IAVs continue to circulate in humans as seasonal influenza. In addition to humans, IAVs have a wide range of host animal species in nature, especially wild aquatic birds, the reservoir hosts of IAVs. The IAVs isolated from or adapted to an avian host are named avian influenza viruses (AIVs), and are of great concern owing to their involvement in the genesis of pandemic and outbreak strains. Moreover, the majority of AIVs persist in wild birds and domestic poultry, and novel variants continue to emerge in birds and other hosts, posing non-negligible threats to host ecology and public health.

Data analysis evidence beyond correlation of a possible causal impact of weather on the COVID-19 spread, mediated by human mobility.

Previous correlative and modeling approaches indicate influences of environmental factors on COVID-19 spread through atmospheric conditions' impact on virus survival and transmission or host susceptibility. However, causal connections from environmental factors to the pandemic, mediated by human mobility, received less attention. We use the technique of Convergent Cross Mapping to identify the causal connections, beyond correlation at the country level, between pairs of variables associated with weather conditions, human mobility, and the number of COVID-19 cases for 32 European states. Here, we present data-based evidence that the relatively reduced number of cases registered in Northern Europe is related to the causal impact of precipitation on people's decision to spend more time at home and that the relatively large number of cases observed in Southern Europe is linked to people's choice to spend time outdoors during warm days. We also emphasize the channels of the significant impact of the pandemic on human mobility. The weather-human mobility connections inferred here are relevant not only for COVID-19 spread but also for any other virus transmitted through human interactions. These results may help authorities and public health experts contain possible future waves of the COVID-19 pandemic or limit the threats of similar human-to-human transmitted viruses.

Novel insights on microbiome dynamics during a gill disease outbreak in farmed rainbow trout (Oncorhynchus mykiss).

The generic term "Gill disease" refers to a wide range of disorders that affect the gills and severely impact salmonid aquaculture systems worldwide. In rainbow trout freshwater aquaculture, various etiological agents causing gill diseases have been described, particularly Flavobacterium and Amoeba species, but research studies suggest a more complex and multifactorial aetiology. Here, a cohort of rainbow trout affected by gill disease is monitored both through standard laboratory techniques and 16S rRNA Next-Generation Sequencing (NGS) analysis during a natural disease outbreak and subsequent antibiotic treatment with Oxytetracycline. NGS results show a clear clustering of the samples between pre- and post-treatment based on the microbial community of the gills. Interestingly, the three main pathogenic bacteria species in rainbow trout (Yersinia ruckeri, Flavobacterium psychrophilum, and Flavobacterium branchiophilum) appear to be weak descriptors of the diversity between pre-treatment and post-treatment groups. In this study, the dynamics of the gill microbiome during the outbreak and subsequent treatment are far more complex than previously reported in the literature, and environmental factors seem of the utmost importance in determining gill disease. These findings present a potential novel perspective on the diagnosis and management of gill diseases, showing the limitations of conventional laboratory methodologies in elucidating the complexity of this disease in rainbow trout. To the authors' knowledge, this work is the first to describe the microbiome of rainbow trout gills during a natural outbreak and subsequent antibiotic treatment. The results of this study suggest that NGS can play a critical role in the analysis and comprehension of gill pathology. Using NGS in future research is highly recommended to gain deeper insights into such diseases correlating gill's microbiome with other possible cofactors and establish strong prevention guidelines.

Bacterial Opsonization Changes Adhesion Interactions between Endothelial Cells and Neutrophils in a Model of Experimental Septicemia.

The influence of non-opsonized and opsonized S. aureus 2879M and E. coli 321 strains on the total strength of interaction between the endothelial cell and neutrophil during the docking process was studied using in vitro model of experimental septicemia. We observed a decrease in the force and work of adhesion between receptors of neutrophils and endothelial cells under the influence of non-opsonized strains and further decrease in the affinity of single interactions between cells under the influence of opsonized S. aureus, which was compensated by an increase in the number of contacts, as well as an increase in the force of adhesion under the influence of opsonized E. coli compared to non-opsonized bacteria, which remained below the control level, while adhesion work reaches the control level. Thus, opsonization of S. aureus aggravates the "immunological uncoupling" between neutrophils and endothelial cells, while opsonization of E. coli reduces the pathological effect compared to non-opsonized bacteria.

Impact of Experimental Tuberculosis on Fertility of Female BALB/c Mice.

The study revealed no effects of pregnancy and childbirth on the course of tuberculosis in female BALB/c mice after aerosol infection with Mycobacterium tuberculosis. However, we demonstrated a negative effect of tuberculosis infection on the fertility of infected females, which manifested in a longer period from mating to pregnancy and in a smaller litter size. Impaired reproductive function in response to the effect of the systemic infectious process was accompanied by the development of immunosuppression confirmed by an immunological test (delayed-type hypersensitivity to tuberculin) and the formation of genital tract dysbiosis during pregnancy and postpartum period.

Kosakonia oryziphila NP19 bacterium acts as a plant growth promoter and biopesticide to suppress blast disease in KDML105 rice.

This study demonstrates that root-associated Kosakonia oryziphila NP19, isolated from rice roots, is a promising plant growth-promoting bioagent and biopesticide for combating rice blast caused by Pyricularia oryzae. In vitro experiments were conducted on fresh leaves of Khao Dawk Mali 105 (KDML105) jasmine rice seedlings. The results showed that NP19 effectively inhibited the germination of P. oryzae fungal conidia. Fungal infection was suppressed across three different treatment conditions: rice colonized with NP19 and inoculated by fungal conidia, a mix of NP19 and fungal conidia concurrently inoculated on the leaves, and fungal conidia inoculation first followed by NP19 inoculation after 30 h. Additionally, NP19 reduced fungal mycelial growth by 9.9-53.4%. In pot experiments, NP19 enhanced the activities of peroxidase (POD) and superoxide dismutase (SOD) by 6.1-63.0% and 3.0-67.7%, respectively, indicating a boost in the plant's defense mechanisms. Compared to the uncolonized control, the NP19-colonized rice had 0.3-24.7% more pigment contents, 4.1% more filled grains per panicle, 26.3% greater filled grain yield, 34.4% higher harvest index, and 10.1% more content of the aroma compound 2-acetyl-1-pyrroline (2AP); for rice colonized with NP19 and infected with P. oryzae, these increases were 0.2-49.2%, 4.6%, 9.1%, 54.4%, and 7.5%, respectively. In field experiments, blast-infected rice that was colonized and/or inoculated with NP19 treatments had 15.1-27.2% more filled grains per panicle, 103.6-119.8% greater filled grain yield, and 18.0-35.8% higher 2AP content. A higher SOD activity (6.9-29.5%) was also observed in the above-mentioned rice than in the blast-infected rice that was not colonized and inoculated with NP19. Following blast infection, NP19 applied to leaves decreased blast lesion progression. Therefore, K. oryziphila NP19 was demonstrated to be a potential candidate for use as a plant growth-promoting bioagent and biopesticide for suppressing rice blast.

Anti-virulence potential of iclaprim, a novel folic acid synthesis inhibitor, against Staphylococcus aureus.

Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. KEY POINTS: • Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm • Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation • In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival.

Genomic diversity, antibiotic resistance, and virulence in South African Enterococcus faecalis and Enterococcus lactis isolates.

This study presents the empirical findings of an in-depth genomic analysis of Enterococcus faecalis and Enterococcus lactis isolates from South Africa. It offers valuable insights into their genetic characteristics and their significant implications for public health. The study uncovers nuanced variations in the gene content of these isolates, despite their similar GC contents, providing a comprehensive view of the evolutionary diversity within the species. Genomic islands are identified, particularly in E. faecalis, emphasizing its propensity for horizontal gene transfer and genetic diversity, especially in terms of antibiotic resistance genes. Pangenome analysis reveals the existence of a core genome, accounting for a modest proportion of the total genes, with 2157 core genes, 1164 shell genes, and 4638 cloud genes out of 7959 genes in 52 South African E. faecalis genomes (2 from this study, 49 south Africa genomes downloaded from NCBI, and E. faecalis reference genome). Detecting large-scale genomic rearrangements, including chromosomal inversions, underscores the dynamic nature of bacterial genomes and their role in generating genetic diversity. The study uncovers an array of antibiotic resistance genes, with trimethoprim, tetracycline, glycopeptide, and multidrug resistance genes prevalent, raising concerns about the effectiveness of antibiotic treatment. Virulence gene profiling unveils a diverse repertoire of factors contributing to pathogenicity, encompassing adhesion, biofilm formation, stress resistance, and tissue damage. These empirical findings provide indispensable insights into these bacteria's genomic dynamics, antibiotic resistance mechanisms, and virulence potential, underlining the pressing need to address antibiotic resistance and implement robust control measures.

Salmonella Typhimurium exploits host polyamines for assembly of the type 3 secretion machinery.

Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.

Evolution of Phytophthora infestans on its potato host since the Irish potato famine.

Phytophthora infestans is a major oomycete plant pathogen, responsible for potato late blight, which led to the Irish Potato Famine from 1845-1852. Since then, potatoes resistant to this disease have been bred and deployed worldwide. Their resistance (R) genes recognize pathogen effectors responsible for virulence and then induce a plant response stopping disease progression. However, most deployed R genes are quickly overcome by the pathogen. We use targeted sequencing of effector and R genes on herbarium specimens to examine the joint evolution in both P. infestans and potato from 1845-1954. Currently relevant effectors are historically present in P. infestans, but with alternative alleles compared to modern reference genomes. The historic FAM-1 lineage has the virulent Avr1 allele and the ability to break the R1 resistance gene before breeders deployed it in potato. The FAM-1 lineage is diploid, but later, triploid US-1 lineages appear. We show that pathogen virulence genes and host resistance genes have undergone significant changes since the Famine, from both natural and artificial selection.

Characteristics and pathogenicity of Vibrio alginolyticus SWS causing high mortality in mud crab (Scylla serrata) aquaculture in Hong Kong.

Introduction: Vibrio alginolyticus is a Gram-negative, rod-shaped bacterium belonging to the family of Vibrionaceae, a common pathogen in aquaculture animals, However, studies on its impact on Scylla serrata (mud crabs) are limited. In this study, we isolated V. alginolyticus SWS from dead mud crab during a disease outbreak in a Hong Kong aquaculture farm, which caused up to 70% mortality during summer. Methods: Experimental infection and histopathology were used to investigate the pathogenicity of V. alginolyticus SWS in S. serrata and validate Koch's postulates. Comprehensive whole-genome analysis and phylogenetic analysis antimicrobial susceptibility testing, and biochemical characterization were also performed. Results: Our findings showed that V. alginolyticus SWS caused high mortality (75%) in S. serrata with infected individuals exhibiting inactivity, loss of appetite, decolored and darkened hepatopancreas, gills, and opaque muscle in the claw. Histopathological analysis revealed tissue damage and degeneration in the hepatopancreas, gills, and claw muscle suggesting direct and indirect impacts of V. alginolyticus SWS infection. Conclusions: This study provides a comprehensive characterization of V. alginolyticus SWS as an emerging pathogen in S. serrata aquaculture. Our findings underscore the importance of ongoing surveillance, early detection, and the development of targeted disease management strategies to mitigate the economic impact of vibriosis outbreaks in mud crab aquaculture.