Bacteriophage最新文献

Staphylococcal pathogenicity islands (SaPIs) are ∼15 kb chromosomally located mobile elements that parasitize "helper" phages which provide a de-repressor protein plus virion and lysis proteins which enable the release of infectious SaPI particles in very high titers. All SaPIs interfere with the reproduction of their helper phages, using 3 different mechanisms. The logic of SaPI reproduction requires that these interference mechanisms do not totally block phage production, as this would be lethal for them as well as for the phage. The discovery of 2 SaPI2 proteins that totally block phage 80 by interfering with late phage transcription was inconsistent with this principle and led to the discovery of a third protein that binds to one of the interference proteins and modulates its activity, thus preventing complete inhibition of the phage. These systems permit the SaPIs to engage in horizontal transfer of unlinked chromosomal genes as well as their own.

A specialized complex, the tail, is the most common strategy employed by bacterial viruses to deliver their genome without disrupting cell integrity. T7 has a short, non-contractile tail formed by a tubular structure surrounded by fibers. Recent studies showed that incubation of the virus with Escherichia coli lipopolysaccharides (LPS) resulted in complete delivery of the viral genome, demonstrating for the first time that LPS are the T7 receptor. Further screening of the bacterial envelope for proteinaceous compounds that affect T7 ejection showed that porins OmpA and OmpF affect viral particle adsorption and infection kinetics, suggesting that these proteins play a role in the first steps of virus-host interaction. Comparison of the structures before and after ejection showed the conformational changes needed in the tail for genome delivery. Structural similarities between T7 and other viruses belonging to the Podoviridae family suggests that they could also follow a similar DNA ejection mechanism.

Antagonistic coevolution between bacteria and phages (reciprocal selection for resistance and infectivity) has been demonstrated in a wide range of natural ecosystems, as well as experimental populations of microbes, yet exploiting knowledge of coevolution for the prophylactic and therapeutic use of phages is under-explored. In this addendum to our recent paper we discuss how real-time coevolution studies using experimental populations of bacteria and phages can provide novel insight into the changes in bacterial phenotypes that result from resistance evolution against coevolving phages, and how this may ultimately improve our understanding of phage therapy and ability to design effective treatments.

It is generally agreed that a bacteriophage-associated phenomenon was first unambiguously observed one-hundred years ago with the findings of Twort in 1915. This was independently followed by complementary observations by d'Hérelle in 1917. D'Hérelle's appreciation of the bacteriophage phenomenon appears to have directly led to the development of phages as antibacterial agents within a variety of contexts, including medical and agricultural. Phage use to combat nuisance bacteria appears to be especially useful where targets are sufficiently problematic, suitably bactericidal phages exist, and alternative approaches are lacking in effectiveness, availability, safety, or cost effectiveness, etc. Phage development as antibacterial agents has been strongest particularly when antibiotics have been less available or useful, e.g., such as in the treatment of chronic infections by antibiotic-resistant bacteria. One relatively under-explored or at least not highly reported use of phages as therapeutic agents has been to combat bacterial infections of the lungs and associated tissues. These infections are diverse in terms of their etiologies, manifestations, and also in terms of potential strategies of phage delivery. Here I review the literature considering the phage therapy of pulmonary and pulmonary-related infections, with emphasis on reports of clinical treatment along with experimental treatment of pulmonary infections using animal models.

Lambda and P22 are members of 2 families of tailed phages and have limited genomic relationships. Both form hybrids with many phages. P22 appears as a hybrid of mixed ancestry. Despite their similarities, lambda and P22 and their relatives form 2 distinct lineages and must be classified separately.

A key event in the lifecycle of a temperate bacteriophage is the choice between lysis and lysogeny upon infection of a susceptible host cell. In a recent paper, we showed that a prolonged period exists after the decision to lysogenize, during which bacteriophage λ can abandon the initial decision, and instead develop lytically, as a response to the accumulation of the late lytic regulatory protein Q. Here, we present evidence that expression of Q does not induce replication of λ DNA, suggesting that the DNA to be packaged into the resulting phage progeny was already present at the time of the initial decision to lysogenize. We summarize our findings in a working model of the key determinants of the duration of the post-decision period during which it is possible for the infected cell to switch from the lysogeny decision to successful lytic development.