ABSTRACT Since the outbreak of coronavirus disease 2019 (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously mutated and evolved, causing several waves of infection. Predicting the evolutionary and epidemiological dynamics of SARS-CoV-2 remains a challenge. This study combines the epidemic data of different variants of SARS-CoV-2 in South Africa to predict their evolutionary and epidemiological dynamics. Based on the susceptible-infectious-recovered-susceptible (SIRS) transmission dynamics, we consider the transmission rate as an evolutionary trait and the disease-deduced mortality and recovery rates as trade-off functions of the trait. Using the adaptive dynamics method, combined with the epidemic data of the five most recent variants in South Africa, we find that South Africa will be continuously invaded and infected by the new mutant strain with a higher transmission rate. In addition, we find that changing the recovery rate by enhancing treatment, for example, will alter the trade-off function and thereby affect the evolutionary dynamics of SARS-CoV-2, which may evolve into a continuously stable strategy. This study is the first to use evolutionary dynamics theory to predict the future evolutionary and epidemiological dynamics of SARS-CoV-2, which is helpful for the government to predict the epidemic dynamics of COVID-19 and to take effective measures in advance, and it is proposed that advancing treatment time and improving treatment efficiency will contribute to disease control.

ABSTRACT Pathogens frequently produce proteins to evade or inhibit host immune responses. One such protein is lymphostatin from attaching and effacing Escherichia coli (also known as lymphocyte inhibitory factor A; LifA), which influences intestinal colonization and inhibits mitogen- and antigen-activated proliferation of T lymphocytes and pro-inflammatory cytokine synthesis. Here, we report the cloning, purification and characterization of a LifA homologue from Chlamydia pecorum. The predicted 382 KDa protein (CPE2_0552) exhibited 36% identity and 55% similarity over 3171 amino acids to lymphostatin from enteropathogenic E. coli strain E2348/69. CPE2_0552 shares glycosyltransferase and cysteine protease motifs required for lymphostatin activity, including similarity in the tertiary structure of these domains predicted by AlphaFold 3. Purified CPE2_0552 did not share the L-shaped globular structure of lymphostatin when analyzed by transmission electron microscopy. CPE2_0552 inhibited concanavalin A-stimulated proliferation of bovine T cells in a concentration-dependent manner, with an inhibitory dose 50 (ID50) of 812 pg/mL. This was 38-fold higher than the ID50 of E. coli E2348/69 lymphostatin tested in parallel on T cells from the same donors (21 pg/mL), but was similar to another LifA homologue from E. coli O157:H7 (ToxB). Moreover, CPE2_0552 inhibited the secretion of interferon gamma (IFNγ), a key cytokine that influences the outcome of Chlamydia infections. At the concentrations at which CPE2_0552 inhibited T lymphocyte proliferation and IFNγ secretion, negligible cytotoxicity was observed after 72 h of stimulation. Our study indicates that E. coli lymphostatin belongs to a wider family of lymphocyte-inhibitory molecules that exist in distantly related bacterial pathogens.

ABSTRACT This study investigated the role of protein disulphide isomerase A4 (PDIA4) in the pathogenesis of coronavirus disease 2019 (COVID-19), focusing on its relationship with disease severity and potential as a biomarker. We analysed a cohort of adult COVID-19 patients with varying disease severity, grouped by vaccination status. Serum levels of PDIA4 and cytokines (interleukin [IL]-6, interferon gamma inducible protein-10 [IP-10], IL-16, monocyte chemoattractant protein‐1 [MCP-1], and platelet-derived growth factor-BB [PDGF-BB]) were measured using enzyme-linked immunosorbent assay and compared among patients with different disease severities. Statistical analyses were performed to assess the correlation between PDIA4 levels, disease severity, and inflammatory markers. Unvaccinated COVID-19 patients with pneumonia had significantly higher PDIA4 levels than those without pneumonia (517.94 ± 264 vs. 284.86 ± 2.24; p = 0.0022). Although unvaccinated patients requiring oxygen support exhibited higher PDIA4 levels than those not requiring oxygen (519.30 ± 269.67 vs. 420.89 ± 240.49; p = 0.4825), the difference was not statistically significant. No significant difference was observed in the PDIA4 levels between unvaccinated patients with and without respiratory failure. Levels of PDIA4 were positively correlated with the levels of IL-16, MCP-1, IP-10, and IL-6 (correlation coefficients: 0.28–0.62), although this correlation was weaker or absent in vaccinated patients. Our findings suggest that PDIA4 is associated with COVID-19 severity and may serve as a potential biomarker of disease progression. Further studies are needed to elucidate the mechanisms by which PDIA4 influences the immune response and assess its potential for therapeutic exploration in COVID-19.

Climate change is predicted to increase the risk of the emergence or re-emergence of infectious diseases. Most, if not all, studies that have explored the possibility of diseases spreading into naive populations have only considered incidence as a measure of disease burden. We argue that, for many diseases, disease severity will be greater in previously unexposed populations than in populations where the disease has been endemic. There have been many examples throughout history of diseases becoming more lethal as they spread into new populations. A classic example of this is the impact on North Americans after the arrival of Europeans. A more recent example is the emergence of Zikaviruses in South America. There are a range of possible explanations for this phenomenon, including the age at first exposure, immunity, and host genetic factors. We need to plan not only for an increase in the incidence of a range of infectious diseases, but also for an increase in the disease burden.

ABSTRACT High-risk lineages of Pseudomonas aeruginosa pose a serious threat to public health, causing severe infections with high mortality rates and limited treatment options. The emergence and rapid spread of the high-risk lineage ST463 in China have further exacerbated this issue. However, the basis of its success in China remains unidentified. In this study, we analyzed a comprehensive dataset of ST463 strains from 2000 to 2023 using whole genome sequencing to unravel the epidemiological characteristics, evolutionary trajectory, and antibiotic resistance profiles. Our findings suggest that ST463 likely originated from a single introduction from North America in 2007, followed by widespread domestic dissemination. Since its introduction, the lineage has undergone significant genomic changes, including the acquisition of three unique regions that enhanced its metabolism and adaptability. Frequent recombination events, along with the burden of bacteriophages, antibiotic resistance genes, and the spread of c1-type (bla KPC-2) plasmid-carrying strains, have played crucial roles in its expansion in China. Mutation analysis reveals adaptive responses to antibiotics and selective pressures on key virulence factors, indicating that ST463 is evolving toward a more pathogenic lifestyle.

ABSTRACT Currently, the Omicron variant of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate globally. In our multiplex respiratory pathogen detection, we identified numerous instances of co-infection with Echovirus (ECHO) among Coronavirus Disease 2019 (COVID-19) patients, which exacerbated the clinical symptoms of these patients. Such co-infections are likely to impact the subsequent medical treatment. To date, there are no reports on the pathogenic mechanisms related to COVID-19 co-infected with ECHO. Therefore, this study employed the TM Widely-Targeted metabolomics approach to analyze the serum metabolomes of COVID-19 patients with single SARS-CoV-2 infection (COVID-19), COVID-19 patients co-infected with ECHO (COVID-19 + ECHO), and healthy individuals (Control) recruited from routine physical examinations during the same period. Concurrent clinical laboratory tests were performed on the patients to reveal the differences in metabolomic characteristics between the COVID-19 patients and the COVID-19 + ECHO patients, as well as to explore potential metabolic pathways that may exacerbate disease progression. Our findings indicate that both clinical examination indicators and the pathways enriched by differential metabolites confirm that patients with dual infection exhibit higher inflammatory and immune responses compared to those with single COVID-19 infections. This difference is likely reflected through abnormalities in the glycerophospholipid metabolic pathway, with the metabolite Sn-Glycero-3-Phosphocholine playing a crucial role in this process. Finally, we established a diagnostic model based on logistic regression using five differential metabolites, which accurately differentiates between the dual infection population and the single COVID-19 infection population (AUC = 0.828).

ABSTRACT The Alongshan virus (ALSV), classified within the Flaviviridae family and belonging to the Jingmenvirus group, is a segmented RNA virus that was first identified in China in 2017. Since then, it has been reported in several Eurasian countries. Although no confirmed fatal cases have been documented, the potential public health risks associated with ALSV are significant and warrant serious attention. The emergence of ALSV has not only broadened the array of tick-borne diseases but has also enriched the research landscape surrounding segmented flaviviruses. Despite these advancements, our understanding of ALSV is still nascent, and its complex infection pathways remain largely unexplored. This review seeks to offer an in-depth examination of ALSV, addressing its biological properties, molecular features, epidemiological data, clinical presentations, and diagnostic methodologies. Our objective is to promote progress in the formulation of preventive, diagnostic, and therapeutic measures for this emerging segmented flavivirus.

ABSTRACT HCO3 – is involved in pH homoeostasis and plays a multifaceted role in human health. HCO3 – has been recognized for its antimicrobial properties and is pivotal in bacterial antibiotic susceptibility. Notably, the interconversion between CO2 and HCO3 –, facilitated by the enzyme carbonic anhydrase (CA), is crucial in tissues infected by pathogens. Studies have highlighted the antimicrobial potency of CA inhibitors, emphasizing the importance of this enzyme in this area. The potential of HCO3 – as an antibiotic adjuvant is evident; its ability to increase virulence in pathogens such as Enterococcus faecalis and Mycobacterium tuberculosis requires meticulous scrutiny. HCO3 – modulates bacterial behaviours in diverse manners: it promotes Escherichia coli O157:H7 colonization in the human gut by altering specific gene expression and, with Pseudomonas aeruginosa, amplifies the effect of tobramycin on planktonic cells while promoting biofilm formation. These multifaceted effects necessitate profound mechanistic exploration before HCO3 – can be considered a promising clinical adjuvant.

ABSTRACT Honey bees are important pollinators in both agriculture and ecosystems, and their health is essential for sustainable human development. Although only two bacteria, Paenibacillus larvae and Melissococcus plutonius, have been identified as bacterial pathogens in honey bee brood for over 100 years, we found three additional Paenibacillus strains (Paenibacillus sp. J27TS7, Paenibacillus azoreducens J34TS1, and Paenibacillus melissococcoides J46TS7) in honey that harmed honey bee brood development. In particular, Paenibacillus sp. J27TS7 was highly virulent in bee larvae (the median lethal dose [LD50] = 12.7 spores/larva) and was comparable to P. larvae (LD50 = 2.3–11.5 spores/larva). Paenibacillus azoreducens J34TS1 showed the second-highest virulence (LD50 = 45.9 spores/larva), and P. melissococcoides J46TS7 was the least virulent (LD50 = 469.0 spores/larva). However, P. melissococcoides was most frequently detected in Japanese honey among the three species, with the highest concentration being 1.8 × 106 spores/mL honey, suggesting its wide distribution in Japanese apiaries. The novel pathogenic Paenibacillus species were categorized into the fast killer (Paenibacillus sp. J27TS7), medium-fast killer (P. melissococcoides), and slow killer (P. azoreducens) like P. larvae strains in terms of the time to kill infected brood; however, histopathological and genome analyses indicated that their pathogenic mechanisms were different from those of P. larvae strains. Moreover, P. melissococcoides showed differences in virulence depending on the lineage of the strain. These findings represent the first discovery of honey bee brood pathogens in more than 100 years and indicate the need to look beyond known pathogens for a comprehensive understanding of honey bee diseases.

ABSTRACT The host restricted pathogens are competently dependent on their respective host for nutritional requirements. The bacterial metabolic pathways are surprisingly varied and remarkably flexible that in turn help them to successfully overcome competition and colonise their host. The metabolic adaptation plays pivotal role in bacterial pathogenesis. The understanding of host-pathogen metabolic crosstalk needs to be prioritized to decipher host-pathogen interactions. The review focuses on various aspects of host pathogen interactions that majorly involves adaptation of bacterial metabolism to counteract immune mechanisms by rectifying metabolic cues that provides pathogen the idea of different anatomical sites and the local physiology of the host. The key set of metabolites that are recognized as centre of competition between host and its pathogens are also briefly discussed. The factors that control the timely expression of virulence of bacterial pathogens is poorly understood. The perspective presented herein will facilitate us with a broader view of molecular mechanisms that modulates the expression of virulence factors in bacterial pathogens. The knowledge of crosslinked metabolic pathways of bacteria and their host will serve to develop novel potential therapeutics.