Transcription Analysis of Streptococcus thermophilus Phages in the Lysogenic State

AbstractThe transcription of prophage genes was studied in two lysogenic Streptococcus thermophilus cells by Northern blot and primer-extension experiments. In the lysogen containing the cos-site phage Sfi21 only two gene regions of the prophage were transcribed. Within the lysogeny module an 1.6-kb-long mRNA started at the promoter of the phage repressor gene and covered also the next two genes, including a superinfection exclusion (sie) gene. A second, quantitatively more prominent 1-kb-long transcript was initiated at the promoter of the sie gene. Another prophage transcript of 1.6-kb length covered a group of genes without database matches that were located between the lysin gene and the right attachment site. The rest of the prophage genome was transcriptionally silent. A very similar transcription pattern was observed for a S. thermophilus lysogen containing the pac-site phage O1205 as a prophage. Prophages from pathogenic streptococci encode virulence genes downstream of the lysin gene. We speculate that temperate phages from lactic streptococci also encode nonessential phage genes (“lysogenic conversion genes”) in this region that increase the ecological fitness of the lysogen to further their own evolutionary success. A comparative genome analysis revealed that many temperate phages from low GC content Gram-positive bacteria encode a variable number of genes in that region and none was linked to known phage-related function. Prophages from pathogenic streptococci encode toxin genes in this region. In accordance with theoretical predictions on prophage–host genome interactions a prophage remnant was detected in S. thermophilus that had lost most of the prophage DNA while transcribed prophage genes were spared from the deletion process

Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

<p>Abstract</p> <p>Background</p> <p>Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti – rotavirus antibodies in a mouse model of rotavirus diarrhea.</p> <p>Results</p> <p>Of the six probiotic bacteria tested, <it>Lactobacillus rhamnosus </it>strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines.</p> <p>Conclusion</p> <p>The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.</p

Widespread distribution of a group I Intron and Its three deletion derivatives in the Lysin Gene of Streptococcus thermophilus Bacteriophages.

Of 62 Streptococcus thermophilus bacteriophages isolated from various ecological settings, half contain a lysingene interrupted by a group IA2 intron. Phage mRNA splicing was demonstrated. Five phages possess a variantform of the intron resulting from three distinct deletion events located in the intron-harbored open readingframe (orf 253). The predicted orf 253 gene sequence showed a significantly lower GC content than thesurrounding intron and lysin gene sequences, and the predicted protein shared a motif with endonucleasesfound in phages from both gram-positive and gram-negative bacteria. A comparison of the phage lysin genesrevealed a clear division between intron-containing and intron-free alleles, leading to the establishment of a14-bp consensus sequence associated with intron possession. The conserved intron was not found elsewhere inthe phage or S. thermophilus bacterial genomes. Folding of the intron RNA revealed secondary structureelements shared with other phage introns: first, a 38-bp insertion between regions P3 and P4 that can be foldedinto two stem-loop structures (shared with introns from Bacillus phage SPO1 and relatives); second, aconserved P7.2 region (shared with all phage introns); third, the location of the stop codon from orf 253 in theP8 stem (shared with coliphage T4 and Bacillus phage SPO1 introns); fourth, orf 253, which has sequencesimilarity with the H-N-H motif of putative endonuclease genes found in introns from Lactococcus, Lactobacillus,and Bacillus phages

Hurdles for Phage Therapy (PT) to Become a Reality

Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since bacteriophages are frequently bacterial host species-specific and can often also infect antibiotic-resistant bacterial cells, they could represent ideal antimicrobials for fighting the antibiotic resistance crisis. The medical use of bacteriophages has become known as phage therapy. It is widely used in Russia, where phage cocktails are sold in pharmacies as an over-the-counter drug. However, no phage product has been registered for medical purposes outside of the former Soviet Union. The current Special Issue of Viruses contains a collection of papers from opinion leaders in the field who explore hurdles to the introduction of phage therapy in western countries. The articles cover diverse topics ranging from patent to regulatory issues, the targeting of suitable bacterial infections, and the selection and characterization of safe and efficient phage cocktails. Phage resistance is discussed, and gaps in our knowledge of phage–bacterium interactions in the mammalian body are revealed, while other articles explore the use of phages in food production and processing

Non‐A to E hepatitis in children: Detecting a novel viral epidemic during the COVID‐19 pandemic

Abstract During the COVID‐19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non‐A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases worldwide, necessitating liver transplantation in 5% and causing death in 2% of patients. It took some effort to clarify the cause of the novel hepatitis epidemic. Researchers were confronted with a polymicrobial viral infection consisting of an adenovirus‐associated virus type 2 (AAV2) infection, co‐occurring with either human adenovirus type 41 (HAdV41) or herpesvirus infections; most prominently human herpesvirus type 6 (HHV‐6). AAV‐2, a small Dependovirus of the Parvovirus family, needs these helper viruses for its replication. AAV2 is used as a vector for liver‐targeting gene therapy but was not previously known to cause acute hepatitis. HAdV41 and HHV‐6 are mostly known to cause diarrhoea and febrile illnesses associated with skin rashes in children, respectively. Except for a few case reports of HHV‐6 hepatitis, HAdV and HHV‐6 are mostly known as major pathogens in immunosuppressed transplantation patients. A potential role of SARS‐CoV‐2 has also been discussed but the most popular hypothesis involves an indirect role of the COVID‐19 pandemic for this novel disease. Exposure to HHV‐6 infections occurs nearly quantitatively during the first year of life. Social distancing measures, followed by the lifting of these measures in 2022 might have caused a delayed exposure to multiple, normally benign childhood viral infections eliciting a dysregulated immune response with pathological effects for liver cells. In the fall of 2022, when these conditions were not longer met, case numbers dwindled. The hypothesis of an unequilibrated immune response instead of intrinsic cytopathic activity of the implicated viruses is further supported by the enrichment of a particular HLA allele in cases over controls

Viral infections at the animal–human interface—Learning lessons from the SARS‐CoV‐2 pandemic

Abstract This Lilliput explores the current epidemiological and virological arguments for a zoonotic origin of the COVID‐19 pandemic. While the role of bats, pangolins and racoon dogs as viral reservoirs has not yet been proven, a spill‐over of a coronavirus infection from animals into humans at the Huanan food market in Wuhan has a much greater plausibility than alternative hypotheses such as a laboratory virus escape, deliberate genetic engineering or introduction by cold chain food products. This Lilliput highlights the dynamic nature of the animal‐human interface for viral cross‐infections from humans into feral white tail deer or farmed minks (reverse zoonosis). Surveillance of viral infections at the animal‐human interface is an urgent task since live animal markets are not the only risks for future viral spill‐overs. Climate change will induce animal migration which leads to viral exchanges between animal species that have not met in the past. Environmental change and deforestation will also increase contact between animals and humans. Developing an early warning system for emerging viral infections becomes thus a societal necessity not only for human but also for animal and environmental health (One Health concept). Microbiologists have developed tools ranging from virome analysis in key suspects such as viral reservoirs (bats, wild game animals, bushmeat) and in humans exposed to wild animals, to wastewater analysis to detect known and unknown viruses circulating in the human population and sentinel studies in animal‐exposed patients with fever. Criteria need to be developed to assess the virulence and transmissibility of zoonotic viruses. An early virus warning system is costly and will need political lobbying. The accelerating number of viral infections with pandemic potential over the last decades should provide the public pressure to extend pandemic preparedness for the inclusion of early viral alert systems

Pandemic potential of poxviruses: From an ancient killer causing smallpox to the surge of monkeypox

Abstract Smallpox caused by the variola virus (VARV) was one of the greatest infectious killers of mankind. Historical records trace back smallpox for at least a millennium while phylogenetic analysis dated the ancestor of VARV circulating in the 20th century into the 19th century. The discrepancy was solved by the detection of distinct VARV sequences first in 17th‐century mummies and then in human skeletons dated to the 7th century. The historical records noted marked variability in VARV virulence which scientists tentatively associated with gene losses occurring when broad‐host poxviruses narrow their host range to a single host. VARV split from camel and gerbil poxviruses and had no animal reservoir, a prerequisite for its eradication led by WHO. The search for residual pockets of VARV led to the discovery of the monkeypox virus (MPXV); followed by the detection of endemic smallpox‐like monkeypox (mpox) disease in Africa. Mpox is caused by less virulent clade 2 MPXV in West Africa and more virulent clade 1 MPXV in Central Africa. Exported clade 2 mpox cases associated with the pet animal trade were observed in 2003 in the USA. In 2022 a world‐wide mpox epidemic infecting more than 80,000 people was noted, peaking in August 2022 although waning rapidly. The cases displayed particular epidemiological characteristics affecting nearly exclusively young men having sex with men (MSM). In contrast, mpox in Africa mostly affects children by non‐sexual transmission routes possibly from uncharacterized animal reservoirs. While African children show a classical smallpox picture, MSM mpox cases show few mostly anogenital lesions, low‐hospitalization rates and 140 fatal cases worldwide. MPXV strains from North America and Europe are closely related, derived from clade 2 African MPXV. Distinct transmission mechanisms are more likely causes for the epidemiological and clinical differences between endemic African cases and the 2022 epidemic cases than viral traits