Monoclonal proliferation of B-cells with two integration sites of bovine leukemia virus proviral DNA in cattle with enzootic bovine leukosis.

The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.

Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.

Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.

Challenges in Managing Treatment-Resistant Mpox Complicated by Severe Superinfection.

Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir. Poor response to antiviral therapy was likely due to his underlying immunocompromised state; however, strain resistance cannot be ruled out given that the patient had started but not completed a 14-day course of tecovirimat 8 months prior, at the time of initial mpox diagnosis. Patients with mpox who are immunocompromised may require extended and additional treatment beyond the standard 14 days of tecovirimat, such as cidofovir, brincidofovir, or intravenous vaccina immune globulin.

Is it in their eyes? Correlation between microorganisms isolated from bronchial aspirates and conjunctival swabs in a Pediatric Intensive Care Unit / ¿Está en sus ojos? Correlación entre microorganismos aislados de aspirados bronquiales e hisopos conjuntivales en una Unidad de Cuidados Intensivos Pediátricos

Objectives. Our observational, retrospective study aimed to determine the correlation between bacteria isolated from bronchial aspirates of pediatric ICU patients (PICU) with respiratory infections and those obtained from conjunctival swabs of the same patients exhibiting clinical conjunctivitis. Material and methods. Throughout the period from 2015 to 2022, we reviewed all clinically significant bronchial aspirates (≥105 CFU/mL) and positive conjunctival swabs obtained from PICU patients. These records were retrieved from the microbiology database, cross-referencing the data to identify patients who tested positive for both during the same clinical episode. Results. The median age of the patients was 5 months (interquartile range: 1-7). Among the cohort, twenty-one patients exhibited positivity in both bronchial aspirate and conjunctival swab samples, showcasing a microbial match in 85.71% of cases (18 out of 21). The most frequently isolated microorganisms were Haemophilus influenzae (55.6%), followed by Pseudomonas aeruginosa (14.3%), Klebsiella aerogenes (9.5%), and Escherichia coli, Stenotrophomonas maltophilia, and Enterobacter cloacae, each accounting for 4.8% of the isolates. Conclusions. Our study demonstrates a strong concordance between the isolated microorganisms from both samples in patients presenting clear symptoms of clinical conjunctivitis. These findings provide a basis for future prospective studies that may leverage conjunctival swabs as a predictive tool for identifying microorganisms involved in respiratory infections. (AU)

Objetivos. Nuestro estudio observacional y retrospectivo tuvo como objetivo determinar la correlación entre las bacterias aisladas de aspirados bronquiales de pacientes de UCI pediátrica (UCIP) con infecciones respiratorias y las obtenidas de hisopos conjuntivales de los mismos pacientes que presentaban conjuntivitis clínica. Material y métodos. A lo largo del periodo comprendido entre 2015 y 2022, se revisaron todos los aspirados bronquiales clínicamente significativos (≥105 UFC/mL) y los hisopos conjuntivalespositivos obtenidos de pacientes de UCIP. Estos registros se recuperaron de la base de datos de microbiología, cruzando los datos para identificar a los pacientes que dieron positivo en ambos durante el mismo episodio clínico. Resultados. La mediana de edad de los pacientes fue de 5 meses (rango intercuartílico: 1-7). Entre la cohorte, veintiún pacientes presentaron positividad tanto en las muestras de aspirado bronquial como en las de hisopo conjuntival, mostrando una coincidencia microbiana en el 85,71% de los casos (18 de 21). Los microorganismos más frecuentemente aislados fueron Haemophilus influenzae (55,6%), seguido de Pseudomonas aeruginosa (14,3%), Klebsiella aerogenes (9,5%) y Escherichia coli, Stenotrophomonas maltophiliay Enterobacter cloacae, cada uno de los cuales representó el 4,8% de los aislamientos. Conclusiones. Nuestro estudio demuestra una fuerte concordancia entre los microorganismos aislados de ambas muestras en pacientes que presentan síntomas claros de conjuntivitis clínica. Estos hallazgos proporcionan una base para futuros estudios prospectivos que podrían aprovechar los hisopos conjuntivales como herramienta predictiva para identificar microorganismos implicados en infecciones respiratorias. (AU)

High HIV diversity, recombination, and superinfection revealed in a large outbreak among persons who inject drugs in Kentucky and Ohio, USA.

We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02_AG-like and CRF02_AG/B, an eighteen-member CRF02_AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread.

Downregulation of endogenous nectin1 in human keratinocytes by herpes simplex virus 1 glycoprotein D excludes superinfection but does not affect NK cell function.

Many viruses downregulate their cognate receptors, facilitating virus replication and pathogenesis via processes that are not yet fully understood. In the case of herpes simplex virus 1 (HSV1), the receptor binding protein glycoprotein D (gD) has been implicated in downregulation of its receptor nectin1, but current understanding of the process is limited. Some studies suggest that gD on the incoming virion is sufficient to achieve nectin1 downregulation, but the virus-encoded E3 ubiquitin ligase ICP0 has also been implicated. Here we have used the physiologically relevant nTERT human keratinocyte cell type - which we have previously shown to express readily detectable levels of endogenous nectin1 - to conduct a detailed investigation of nectin1 expression during HSV1 infection. In these cells, nectin1, but not nectin2 or the transferrin receptor, disappeared from the cell surface in a process that required virus protein synthesis rather than incoming virus, but did not involve virus-induced host shutoff. Furthermore, gD was not only required but was sufficient for nectin1 depletion, indicating that no other virus proteins are essential. NK cells were shown to be activated in the presence of keratinocytes, a process that was greatly inhibited in cells infected with wild-type virus. However, degranulation of NK cells was also inhibited in ΔgD-infected cells, indicating that blocking of NK cell activation was independent of gD downregulation of nectin1. By contrast, a superinfection time-course revealed that the ability of HSV1 infection to block subsequent infection of a GFP-expressing HSV1 was dependent on gD and occurred in line with the timing of nectin1 downregulation. Thus, the role of gD-dependent nectin1 impairment during HSV infection is important for virus infection, but not immune evasion, which is achieved by other mechanisms.

The host transcriptional response to superinfection by influenza A virus and Streptococcus pneumoniae.

Secondary bacterial challenges during influenza virus infection "superinfection") cause excessive mortality and hospitalization. Here, we present a longitudinal study of bulk gene expression changes in murine lungs during superinfection, with an initial influenza A virus infection and a subsequent Streptococcus pneumoniae infection. In addition to the well-characterized impairment of the host response, we identified superinfection-specific alterations in the global transcriptional program that are linked to the host's ability to resist the pathogens. Particularly, whereas superinfected mice manifested an excessive rapid induction of the resistance-to-infection program, there was a substantial tissue-level rewiring of this program: upon superinfection, interferon-regulated genes were switched from positive to negative correlations with the host's resistance state, whereas genes of fatty acid metabolism switched from negative to positive correlations with resistance states. Thus, the transcriptional resistance state in superinfection is reprogrammed toward repressed interferon signaling and induced fatty acid metabolism. Our findings suggest new insights into a tissue-level remodeling of the host defense upon superinfection, providing promising targets for future therapeutic interventions. IMPORTANCE: Secondary bacterial infections are the most frequent complications during influenza A virus (IAV) pandemic outbreaks, contributing to excessive morbidity and mortality in the human population. Most IAV-related deaths are attributed to Streptococcus pneumoniae (SP) infections, which usually begin within the first week of IAV infection in the respiratory tracts. Here, we focused on longitudinal transcriptional responses during a superinfection model consisting of an SP infection that follows an initial IAV infection, comparing superinfection to an IAV-only infection, an SP-only infection, and control treatments. Our longitudinal data allowed a fine analysis of gene expression changes during superinfection. For instance, we found that superinfected mice exhibited rapid gene expression induction or reduction within the first 12 h after encountering the second pathogen. Cell proliferation and immune response activation processes were upregulated, while endothelial processes, vasculogenesis, and angiogenesis were downregulated, providing promising targets for future therapeutic interventions. We further analyzed the longitudinal transcriptional responses in the context of a previously defined spectrum of the host's resistance state, revealing superinfection-specific reprogramming of resistance states, such as reprogramming of fatty acid metabolism and interferon signaling. The reprogrammed functions are compelling new targets for switching the pathogenic superinfection state into a single-infection state.

A dynamic nomogram to predict invasive fungal super-infection during healthcare-associated bacterial infection in intensive care unit patients: an ambispective cohort study in China.

Objectives: Invasive fungal super-infection (IFSI) is an added diagnostic and therapeutic dilemma. We aimed to develop and assess a nomogram of IFSI in patients with healthcare-associated bacterial infection (HABI). Methods: An ambispective cohort study was conducted in ICU patients with HABI from a tertiary hospital of China. Predictors of IFSI were selected by both the least absolute shrinkage and selection operator (LASSO) method and the two-way stepwise method. The predictive performance of two models built by logistic regression was internal-validated and compared. Then external validity was assessed and a web-based nomogram was deployed. Results: Between Jan 1, 2019 and June 30, 2023, 12,305 patients with HABI were screened in 14 ICUs, of whom 372 (3.0%) developed IFSI. Among the fungal strains causing IFSI, the most common was C.albicans (34.7%) with a decreasing proportion, followed by C.tropicalis (30.9%), A.fumigatus (13.9%) and C.glabrata (10.1%) with increasing proportions year by year. Compared with LASSO-model that included five predictors (combination of priority antimicrobials, immunosuppressant, MDRO, aCCI and S.aureus), the discriminability of stepwise-model was improved by 6.8% after adding two more predictors of COVID-19 and microbiological test before antibiotics use (P<0.01).And the stepwise-model showed similar discriminability in the derivation (the area under curve, AUC=0.87) and external validation cohorts (AUC=0.84, P=0.46). No significant gaps existed between the proportion of actual diagnosed IFSI and the frequency of IFSI predicted by both two models in derivation cohort and by stepwise-model in external validation cohort (P=0.16, 0.30 and 0.35, respectively). Conclusion: The incidence of IFSI in ICU patients with HABI appeared to be a temporal rising, and our externally validated nomogram will facilitate the development of targeted and timely prevention and control measures based on specific risks of IFSI.

Japanese encephalitis virus inhibits superinfection of Zika virus in cells by the NS2B protein.

Superinfection exclusion (SIE) is a phenomenon in which a preexisting infection prevents a secondary infection. SIE has been described for several flaviviruses, such as West Nile virus vs Nhumirim virus and Dengue virus vs yellow fever virus. Zika virus (ZIKV) is an emerging flavivirus posing threats to human health. The SIE between ZIKV and Japanese encephalitis virus (JEV) is investigated in this study. Our results demonstrate for the first time that JEV inhibits ZIKV infection in both mammalian and mosquito cells, whether co-infects or subsequently infects after ZIKV. The exclusion effect happens at the stage of ZIKV RNA replication. Further studies show that the expression of JEV NS2B protein is sufficient to inhibit the replication of ZIKV, and the outer membrane region of NS2B (46-103 aa) is responsible for this SIE. JEV infection and NS2B expression also inhibit the infection of the vesicular stomatitis virus. In summary, our study characterized a SIE caused by JEV NS2B. This may have potential applications in the prevention and treatment of ZIKV or other RNA viruses.IMPORTANCEThe reemerged Zika virus (ZIKV) has caused severe symptoms in humans and poses a continuous threat to public health. New vaccines or antiviral agents need to be developed to cope with possible future pandemics. In this study, we found that infection of Japanese encephalitis virus (JEV) or expression of NS2B protein well inhibited the replication of ZIKV. It is worth noting that both the P3 strain and vaccine strain SA14-14-2 of JEV exhibited significant inhibitory effects on ZIKV. Additionally, the JEV NS2B protein also had an inhibitory effect on vesicular stomatitis virus infection, suggesting that it may be a broad-spectrum antiviral factor. These findings provide a new way of thinking about the prevention and treatment of ZIKV.

Establishment of a superinfection exclusion method for pestivirus titration using a recombinant reporter pestiviruses.

Pestiviruses are classified into two biotypes based on their cytopathogenicity. As the majority of pestivirus field isolates are noncytopathogenic, their titration requires alternative methods rather than direct observation of cytopathogenic effects, such as immunostaining using specific antibodies or interference with cytopathogenic strains. However, these methods require microscopic observation to assess virus growth, which is time- and labor-intensive, especially when handling several samples. In this study, we developed a novel luciferase-based pestivirus titration method using the superinfection exclusion phenomenon with recombinant reporter pestiviruses that possessed an 11-amino-acid subunit derived from NanoLuc luciferase (HiBiT). In this method, swine kidney cells were inoculated with classical swine fever virus (CSFV) and superinfected with the reporter CSFV vGPE-/HiBiT 5 days postinoculation. Virus titer was determined based on virus growth measured in luminescence using the culture fluid 3 days after superinfection; the resultant virus titer was comparable to that obtained by immunoperoxidase staining. Furthermore, this method has proven to be applicable for the titration of border disease virus (BDV) by superinfection with both the homologous reporter BDV and heterologous reporter CSFV, suggesting that this novel virus titration method is a simple technique for automated virus detection based on the luciferase system.

A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection.

Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against S. pneumoniae serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4+ T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.

Bacterial Community- and Hospital-Acquired Pneumonia in Patients with Critical COVID-19-A Prospective Monocentric Cohort Study.

The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and Staphylococcus aureus. Notably, no strains of Streptococcus pneumoniae were detected, and only a single strain each of Haemophilus influenzae and Moraxella catarrhalis was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).

Is it in their eyes? Correlation between microorganisms isolated from bronchial aspirates and conjunctival swabs in a Pediatric Intensive Care Unit.

OBJECTIVE: Our observational, retrospective study aimed to determine the correlation between bacteria isolated from bronchial aspirates of pediatric ICU patients (PICU) with respiratory infections and those obtained from conjunctival swabs of the same patients exhibiting clinical conjunctivitis. METHODS: Throughout the period from 2015 to 2022, we reviewed all clinically significant bronchial aspirates (≥105 CFU/mL) and positive conjunctival swabs obtained from PICU patients. These records were retrieved from the microbiology database, cross-referencing the data to identify patients who tested positive for both during the same clinical episode. RESULTS: The median age of the patients was 5 months (interquartile range: 1-7). Among the cohort, twenty-one patients exhibited positivity in both bronchial aspirate and conjunctival swab samples, showcasing a microbial match in 85.71% of cases (18 out of 21). The most frequently isolated microorganisms were Haemophilus influenzae (55.6%), followed by Pseudomonas aeruginosa (14.3%), Klebsiella aerogenes (9.5%), and Escherichia coli, Stenotrophomonas maltophilia, and Enterobacter cloacae, each accounting for 4.8% of the isolates. CONCLUSIONS: Our study demonstrates a strong concordance between the isolated microorganisms from both samples in patients presenting clear symptoms of clinical conjunctivitis. These findings provide a basis for future prospective studies that may leverage conjunctival swabs as a predictive tool for identifying microorganisms involved in respiratory infections.

High-Grade Infection after Branched Endovascular Aortic Repair in Patient with Recent COVID-19 Hospitalization.

In the context of the COVID-19 pandemic, the global healthcare landscape has undergone significant transformations, particularly impacting the management of complex medical conditions such as aortic aneurysms. This study focuses on a 76-year-old female patient with a history of extensive cardiovascular surgeries, including aortic valve replacement, Bentall operation, and Frozen Elephant Trunk procedure, who presented with a type II thoracoabdominal aortic aneurysm post-COVID-19 recovery. A comprehensive frailty assessment using the Modified Frailty Index and a two-phase endovascular approach for aneurysm treatment, considering the patient's frailty and complex medical history was performed. Upon successful aneurysm management, the patient's postoperative course was complicated by COVID-19 reinfection and Enterococcus faecalis superinfection, highlighting the increased risk of bacterial superinfections and the challenges posed by antimicrobial resistance in COVID-19 patients. The study underscores the necessity of vigilant postoperative surveillance and a multidisciplinary approach in managing such complex cases, highlighting the importance of personalized care strategies, integrating cardiovascular and infectious disease management, and adapting healthcare practices to the unique challenges of the pandemic. This case contributes to the evolution of knowledge on managing aortic aneurysms in the COVID-19 era, advocating for patient-centric treatment approaches and continuous research into long-term patient outcomes.

Bacteriophage P22 SieA-mediated superinfection exclusion.

Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. Salmonella phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the c2 (repressor), gtrABC, sieA, and sieB genes. Here we report that the P22-encoded SieA protein is necessary and sufficient for exclusion by the SieA system and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants that overcome the SieA block were isolated, and they have amino acid changes in the C-terminal regions of the gene 16 and 20 encoded ejection proteins. Three different single-amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in phage target specificity. Our data strongly suggest a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.IMPORTANCEThe ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called "superinfection exclusion." A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.

Community-acquired and hospital-acquired bacterial co-infections in patients hospitalized with Covid-19 or influenza: a retrospective cohort study.

BACKGROUND: Bacterial co-infections are believed to be less frequent in patients with Covid-19 than influenza, but frequencies varied between studies. METHODS: This single-center retrospective, propensity score-matched analysis included adult patients with Covid-19 or influenza admitted to normal-care wards between 02/2014 and 12/2021. Covid-19 cases were propensity score matched to influenza cases at a 2:1 ratio. Community-acquired and hospital-acquired bacterial co-infections were defined as positive blood or respiratory cultures ≤ 48 h or > 48 h after hospital admission, respectively. The primary outcome was comparison of community-acquired and hospital-acquired bacterial infections between patients with Covid-19 and influenza in the propensity score-matched cohort. Secondary outcomes included frequency of early and late microbiological testing. RESULTS: A total of 1337 patients were included in the overall analysis, of which 360 patients with Covid-19 were matched to 180 patients with influenza. Early (≤ 48 h) microbiological sampling was performed in 138 (38.3%) patients with Covid-19 and 75 (41.7%) patients with influenza. Community-acquired bacterial co-infections were found in 14 (3.9%) of 360 patients with Covid-19 and 7 (3.9%) of 180 patients with influenza (OR 1.0, 95% CI 0.3-2.7). Late (> 48 h) microbiological sampling was performed in 129 (35.8%) patients with Covid-19 and 74 (41.1%) patients with influenza. Hospital-acquired bacterial co-infections were found in 40 (11.1%) of 360 patients with Covid-19 and 20 (11.1%) of 180 patients with influenza (OR 1.0, 95% CI 0.5-1.8). CONCLUSION: The rate of community-acquired and hospital-acquired bacterial co-infections was similar in hospitalized Covid-19 and influenza patients. These findings contrast previous literature reporting that bacterial co-infections are less common in Covid-19 than influenza.

A case of fatal monkeypox infection: necropsy and molecular findings, with some considerations related to clinical management.

OBJECTIVE: Human monkeypox (mpox) is usually self-limited infection; however, rising data show a worse outcome in patients with impaired immune status, particularly those co-infected with HIV [Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS et al. Mpox in people with advanced HIV infection: A global case series. Lancet. 2023; 401:939-49. DOI:https://doi.org/10.1016/S0140-6736(23)00273-8] [Govind A, Lazarte SM, Kitchell E, Chow JY, Estelle CD, Fixsen E et al. Severe mpox infections in people with uncontrolled human immunodeficiency virus (HIV). Clin Infect Dis. 2023; 76:1843-6. DOI:https://doi.org/10.1093/cid/ciad052]. METHODS: We report the clinical, pathological, and molecular study of a patient with mpox infection and a late HIV diagnosis, with fatal outcome. RESULTS: Necropsy revealed visceral spread of mpox. Mpox virus was sequenced twice during the admission, uncovering an emerging mutation near a genomic region where mutations associated with tecovirimat resistance have been documented. DISCUSSION: Monkeypox can manifest as an opportunistic infection in individuals with advanced HIV-associated immunosuppression.

Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

Immunobiotic Ligilactobacillus salivarius FFIG58 Confers Long-Term Protection against Streptococcus pneumoniae.

Previously, we isolated potentially probiotic Ligilactobacillus salivarius strains from the intestines of wakame-fed pigs. The strains were characterized based on their ability to modulate the innate immune responses triggered by the activation of Toll-like receptor (TLR)-3 or TLR4 signaling pathways in intestinal mucosa. In this work, we aimed to evaluate whether nasally administered L. salivarius strains are capable of modulating the innate immune response in the respiratory tract and conferring long-term protection against the respiratory pathogen Streptococcus pneumoniae. Infant mice (3-weeks-old) were nasally primed with L. salivarius strains and then stimulated with the TLR3 agonist poly(I:C). Five or thirty days after the last poly(I:C) administration mice were infected with pneumococci. Among the strains evaluated, L. salivarius FFIG58 had a remarkable ability to enhance the protection against the secondary pneumococcal infection by modulating the respiratory immune response. L. salivarius FFIG58 improved the ability of alveolar macrophages to produce interleukin (IL)-6, interferon (IFN)-γ, IFN-ß, tumor necrosis factor (TNF)-α, IL-27, chemokine C-C motif ligand 2 (CCL2), chemokine C-X-C motif ligand 2 (CXCL2), and CXCL10 in response to pneumococcal challenge. Furthermore, results showed that the nasal priming of infant mice with the FFIG58 strain protected the animals against secondary infection until 30 days after stimulation with poly(I:C), raising the possibility of using nasally administered immunobiotics to stimulate trained immunity in the respiratory tract.