MicrobiologyBytes

“Rather than destroying HIV, a proposed treatment would embrace its infectious abilities, sending the virus into competition with a harmless, stripped-down version of itself. Dubbed therapeutic interfering particles, or TIPs, these engineered viral scraps would ride with HIV as it spreads from person to person. By out-competing HIV for cellular resources, the TIPs might slow its progression and lower infection rates. “A virus can’t replicate without a host, and similarly TIPs can’t replicate without HIV. It would piggyback on the virus,” said biophysicist and virologist Leor Weinberger of the University of California, San Diego, who modeled the epidemiology of TIPs in a study March 17 in PLoS Computational Biology. “It’s basically a virus of a virus.” Approximately 33 million people now carry HIV, or human immunodeficiency virus, which infects immune system cells that defend against disease. The virus gradually destroys them, taking away the body’s ability to protect itself. Without treatment, HIV infection leads to AIDS in about 10 years. Death follows soon after as common diseases overcome the body.”

via Piggyback Virus Could Curb HIV Pandemic | Wired.com

Source:
Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies. (2011) PLoS Comput Biol 7(3): e1002015. doi:10.1371/journal.pcbi.1002015

Bacteriophages are the most numerous biological entities in the biosphere, with an estimated 10³¹ particles. The global population is highly dynamic with an estimated 10²³ phage infections per second, and has likely been evolving for perhaps two to four billion years. Not surprisingly, this has given rise to a genetically highly diverse population. Most bacteriophages do not extend their host range beyond a single bacterial genus, and host specificity likely offers a substantial impediment to the free exchange of genetic material between phages of different bacterial hosts. Consequently, it is unusual to find extensive nucleotide sequence similarity among phages of different hosts; such phages often share few if any genes identifiable through amino acid sequence comparisons.

Remarkably, phages capable of infecting a single bacterial species can also be highly diverse, as are for example the genetically distinct DNA phages of Escherichia coli, such as φX174, M13, lambda, T1, T4, T5, and T7. This is further exemplified with the mycobacteriophages – viruses infecting mycobacterial hosts – of which sixty-two genomes of phages known to infect Mycobacterium smegmatis mc2155 have been sequenced. All of these are dsDNA tailed phages, restricted to two morphotypes, the Siphoviridae and the Myoviridae.

This paper describes the isolation and characterization of new mycobacteriophages by student microbiologists, a valuble contribution to our understanding of these organisms.

Expanding the Diversity of Mycobacteriophages: Insights into Genome Architecture and Evolution. (2011) PLoS ONE 6(1): e16329. doi:10.1371/journal.pone.0016329
Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

Bacteria constantly encounter numerous enemies in microbial communities. For example, ubiquitous bacteriophages, i.e. parasitic viruses that replicate within bacterial cells, can effectively constrain bacterial survival in nature. A wide array of laboratory experiments has shown that bacteriophages can drive rapid bacterial evolution by imposing strong selection for phage-resistant bacteria. Furthermore, phage-resistance has been shown to correlate negatively with some other bacterial life-history traits, such as growth efficiency and motility, which both are important traits for bacterial pathogenicity. Motility, for example, helps pathogens colonise suitable niches within the host, while growth efficiency can determine how fast bacteria can exploit their hosts. If phage-resistance leads to trade-off with bacterial virulence factors phages could potentially select for lowered bacterial pathogenicity in environmental reservoirs.

This study investigates how parasitic phages and thermal environment affect the evolution of bacterial pathogenicity traits in vitro, and how these changes correlate with bacterial virulence in vivo.

High Temperature and Bacteriophages Can Indirectly Select for Bacterial Pathogenicity in Environmental Reservoirs. (2011) PLoS ONE 6(3): e17651. doi:10.1371/journal.pone.0017651
The coincidental evolution hypothesis predicts that traits connected to bacterial pathogenicity could be indirectly selected outside the host as a correlated response to abiotic environmental conditions or different biotic species interactions. To investigate this, an opportunistic bacterial pathogen, Serratia marcescens, was cultured in the absence and presence of the lytic bacteriophage PPV (Podoviridae) at 25°C and 37°C for four weeks (N = 5). At the end, we measured changes in bacterial phage-resistance and potential virulence traits, and determined the pathogenicity of all bacterial selection lines in the Parasemia plantaginis insect model in vivo. Selection at 37°C increased bacterial motility and pathogenicity but only in the absence of phages. Exposure to phages increased the phage-resistance of bacteria, and this was costly in terms of decreased maximum population size in the absence of phages. However, this small-magnitude growth cost was not greater with bacteria that had evolved in high temperature regime, and no trade-off was found between phage-resistance and growth rate. As a result, phages constrained the evolution of a temperature-mediated increase in bacterial pathogenicity presumably by preferably infecting the highly motile and virulent bacteria. In more general perspective, our results suggest that the traits connected to bacterial pathogenicity could be indirectly selected as a correlated response by abiotic and biotic factors in environmental reservoirs.

In 2011 the World Health Organization (WHO) plans to announce its recommendation regarding the final destruction of all known remaining smallpox virus stockpiles. Smallpox, an ancient human scourge of unparalleled destructive importance throughout most of recorded human history, is believed to have emerged in the Middle East some 6,000–10,000 years ago from either camelpox or the gerbil-specific taterapox. It holds a status as one of the great killers in all human history, having produced the horrific deaths of up to 500 million persons in just the 20th century alone. At first glance, the answer to this conundrum – whether or not smallpox should be forever relegated to the autoclave of extinction – might seem an easy one. Beaten back by the Jenner vaccine first proposed in 1796, smallpox was finally declared eradicated in 1980, in one of the most profound public health achievements in human history. Since that time, WHO has made it generally known that they would like to see the elimination of all remaining variola stockpiles and made the United States and Russia the repository for all remaining stocks. At the 60th Annual World Health Assembly in 2007, the organization postponed the final decision for any recommended destruction deadline until their next meeting in 2011.

Should Remaining Stockpiles of Smallpox Virus (Variola) Be Destroyed? Emerging Infectious Diseases 17(4) April 2011

Vaccines play a fundamental role in modern medicine and the introduction of Edward Jenner’s smallpox vaccine in 1798 marked an important turning point in the battle against infectious disease (Jenner, 1798). With the notable exceptions of smallpox and rabies, many of the early advances made in vaccinology during the 18th and 19th centuries were focused primarily on bacterial pathogens. These initial studies reflect the tools that were developed by early microbiologists to grow and study important pathogenic bacteria as well as some of the challenges faced by virologists prior to the advent of modern tissue culture technologies. During the 20th century, new viral vaccines against yellow fever, influenza, polio, measles, mumps, rubella, and others emerged. There are now 14 vaccines licensed in the USA that are directed against viral pathogens.

Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology. (2011) 411(2): 206-215
Vaccines play a vital role in protecting the host against infectious disease. The most effective licensed vaccines elicit long-term antigen-specific antibody responses by plasma cells in addition to the development of persisting T cell and B cell memory. The relative contributions of these different immune cell subsets are context-dependent and vary depending on the attributes of the vaccine (i.e., live/attenuated, inactivated, and subunit) as well as the biology of the pathogen in question. For relatively simple vaccines against bacterial antigens (e.g., tetanus toxin) or invariant viruses, the immunological correlates of protection are well-characterized. For more complex vaccines against viruses, especially those that mutate or cause latent infections, it is more difficult to define the specific correlates of immunity. This often requires observational/natural history studies, clinical trials, or experimental evaluation in relevant animal models in order for immunological correlates to be determined or extrapolated. In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease.

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• How do you make a vaccine against Ebola virus?
• Dengue virus infection activates the unfolded protein response
• HIV vaccines – bad news, good news

A previously unrecognized severe febrile illness in China has been traced to a novel bunyavirus, possibly transmitted by ticks. Characterized by severe fever and thrombocytopenia, the illness had an initial case fatality rate of 30%. Since June 2009, investigators have documented the presence of the virus in 171 patients from six regions in central and northeastern China, and the infection proved fatal in 12% of cases. The virus invaded multiple cells, but primarily thrombocytes and leukocytes. Multi-organ failure developed rapidly, as reflected by elevated liver enzymes, creatine kinase, and lactate dehydrogenase. A causal relationship between the virus and the illness has yet to be established. However, epidemiologic, clinical, and laboratory data strongly implicate the virus in the febrile illness, the researchers reported online in the New England Journal of Medicine.

via Medical News: New Viral Illness in China Linked to Ticks

Source:

Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China. NEJM March 16 2011 doi: 10.1056/NEJMoa1010095

Iron is a vital nutrient for virtually all forms of life. The requirement for iron is based on its role in cellular processes ranging from energy generation and DNA replication to oxygen transport and protection against oxidative stress. Bacterial pathogens are not exempt from this iron requirement, as these organisms must acquire iron within their vertebrate hosts in order to replicate and cause disease. This paper describes how they do that.

The Battle for Iron between Bacterial Pathogens and Their Vertebrate Hosts. (2010) PLoS Pathog 6(8): e1000949. doi:10.1371/journal.ppat.1000949

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• How bacteria capture iron from heme
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During the past three decades, research using the transforming proteins of small DNA tumor viruses such as human adenoviruses (HAdvs), SV40 and human papillomaviruses (HPVs) has illuminated crucial cellular pathways that control proliferation and oncogenic transformation of mammalian cells. Owing to their small genome size, these viruses are heavily dependent on the host cell machineries to express their genes and replicate their DNA. Because these viruses generally replicate in terminally differentiated quiescent target cells, the viral genes expressed during the early phase of the virus life cycle subvert the host cell cycle, inducing transient proliferation of the infected cells to generate a permissive S-phase state to facilitate viral replication. In non-permissive cells, these viruses express only their early genes, which induce cell proliferation, resulting in abortive infection. A fraction of the infected cells recover, and assume oncogenic properties as a result of continued expression of a subset of viral early genes, referred to as ‘transforming genes’. Transduction of subgenomic DNA fragments containing the transforming genes also achieves transformation of the target cells in significant numbers. Defined viral mutants and transduction of isolated genes have been widely used for molecular genetic analysis of viral transforming genes.

Researchers have used biochemical approaches to identify cellular proteins associated with viral proteins to elucidate the mechanisms through which the transforming proteins of small DNA tumor viruses subvert the cell cycle and elicit oncogenic cell transformation. This approach revealed the interaction of viral transforming proteins with tumor-suppressor proteins such as p53 and the retinoblastoma (pRb) protein. The transforming proteins of HAdvs, SV40 and HPVs share common mechanisms of cell transformation, because they target the same cell-cycle regulatory proteins, such as p53 and the pRb family proteins. This paper discusses the role of adenovirus E1A protein in transformation.

Opposing oncogenic activities of small DNA tumor virus transforming proteins. Trends Microbiol. Feb 15 2011 doi: 10.1016/j.tim.2011.01.003
The E1A gene of species C human adenovirus is an intensely investigated model viral oncogene that immortalizes primary cells and mediates oncogenic cell transformation in cooperation with other viral or cellular oncogenes. Investigations using E1A proteins have illuminated important paradigms in cell proliferation and about the functions of cellular proteins such as the retinoblastoma protein. Studies with E1A have led to the unexpected discovery that E1A also suppresses cell transformation and oncogenesis. Here, I review our current understanding of the transforming and tumor-suppressive functions of E1A, and how E1A studies led to the discovery of a related tumor-suppressive function in benign human papillomaviruses. The potential role of these opposing functions in viral replication in epithelial cells is also discussed.

Related:

• MicroRNA regulation of tumor-killing viruses
• Hepatitis B and C Viruses and Hepatocellular Carcinoma
• Vaccines To Prevent Infections by Oncoviruses

Biologists debated for more than 200 years about which organisms should be counted as fungi. In less than 5 years, DNA sequencing provided a multitude of new characters for analysis and identified about 10 phyla as members of the monophyletic kingdom Fungi. Mycologists benefited from early developments applied directly to fungi. The “universal primers,” so popular in the early 1990s for the polymerase chain reaction (PCR), actually were designed for fungi. Use of the PCR was a monumental advance for those who studied minute, often unculturable, organisms.

Fungi interact with all major groups of organisms. By their descent from an ancestor shared with animals about a billion years ago plus or minus 500 million years, the fungi constitute a major eukaryotic lineage equal in numbers to animals and exceeding plants. But how many fungal species are there?

The Fungi: 1, 2, 3 … 5.1 million species? American Journal of Botany, March 2 2011 doi: 10.3732/ajb.1000298
Premise of the study: Fungi are major decomposers in certain ecosystems and essential associates of many organisms. They provide enzymes and drugs and serve as experimental organisms. In 1991, a landmark paper estimated that there are 1.5 million fungi on the Earth. Because only 70000 fungi had been described at that time, the estimate has been the impetus to search for previously unknown fungi. Fungal habitats include soil, water, and organisms that may harbor large numbers of understudied fungi, estimated to outnumber plants by at least 6 to 1. More recent estimates based on high-throughput sequencing methods suggest that as many as 5.1 million fungal species exist.
Methods: Technological advances make it possible to apply molecular methods to develop a stable classification and to discover and identify fungal taxa.
Key results: Molecular methods have dramatically increased our knowledge of Fungi in less than 20 years, revealing a monophyletic kingdom and increased diversity among early-diverging lineages. Mycologists are making significant advances in species discovery, but many fungi remain to be discovered.
Conclusions: Fungi are essential to the survival of many groups of organisms with which they form associations. They also attract attention as predators of invertebrate animals, pathogens of potatoes and rice and humans and bats, killers of frogs and crayfish, producers of secondary metabolites to lower cholesterol, and subjects of prize-winning research. Molecular tools in use and under development can be used to discover the world’s unknown fungi in less than 1000 years predicted at current new species acquisition rates.

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