MicrobiologyBytes

The first publications exploring the interface between sexually transmitted infections (STIs) and the Internet appeared in the 26 July 2000 issue of the Journal of the American Medical Association. In one article, Klausner et al. described a cluster of early syphilis cases among men having sex with men (MSM) who had met each other online. In the second article in the same issue, McFarlane et al. reported on a survey among clients of the Denver HIV counseling and testing program, showing that among MSM visiting the site, 25% had sex with at least one partner first met on the Internet. Together, these articles suggested that the Internet was emerging as a new risk environment for STIs and HIV. Since the publication of these articles, numerous studies have been conducted and published that have further investigated the role of the Internet, both as an STI/HIV risk “venue” as well as a potential place for the delivery of STI/HIV prevention services.

In recent years, the Internet and its users have undergone a fundamental transformation. Originally, the Internet was designed to allow access of information provided by the publisher of a given website. Although websites have become very sophisticated in how this information is presented and while the information given can be tailored to the individual user, the information stream is predominantly unidirectional from the website to the user, and the content of the site is determined by its owner. Examples include sites that aim to convey general information about businesses or organizations, for example, the website of the Centers for Disease Control and Prevention, or allow for minimal manipulation of personalized information, such as online banking or bill payment. In Internet terms, this use of the Internet is referred to as Web 1.0. By contrast, Web 2.0 comprises Internet applications in which the information stream is more or less reversed. Here, the content of a website is mostly driven by the users of the site. This information can take multiple forms, including a variety of uploaded file formats (text, graphics, audio, video), blogs (web-logs), vlogs (video logs), chats, etc. Social networking sites, including YouTube, MySpace, and FaceBook are among the prime examples of the Web 2.0 applications that have revolutionized Internet use in the last decade.

In this article, the authors discuss the implications of the shift from Web 1.0 to Web 2.0 technology on sexual health from three perspectives: the Internet as an STI risk environment, the Internet as a venue for STI prevention, and, finally, the Internet as a tool for STI service and prevention providers. The growth of the Internet as a communication medium has had far-reaching consequences for STI/HIV prevention ranging from a venue for partner recruitment with potential risk as well as prevention benefits, to the use of the Internet as a place to deliver STI/HIV prevention services in a variety of more or less interactive formats, and finally as a tool for the development of a prevention work force. However, while the Internet has great potential as an important STI/HIV prevention medium, it appears that the greatest potential is yet untapped and that the providers of these services are considerably lagging behind their target audience in the creative and innovative uses of the new medium.

Web 2.0 and beyond: risks for sexually transmitted infections and opportunities for prevention. Curr Opin Infect Dis. 2009 22(1): 67-71
The continued growth of the Internet as a communication medium has had major implications for the transmission and prevention of sexually transmitted infections (STIs). The purpose of this review is to describe recent developments in this rapidly changing environment. The interface between the Internet and STIs is described from three perspectives: the Internet as a risk environment, that is, a place where prospective, potentially STI-infected, sex partners can be recruited; the Internet as a venue where public health prevention interventions aimed at STIs and HIV prevention can be placed; and the Internet as an increasingly important work environment for all STI prevention disciplines. The review highlights recent developments and identifies potential avenues for future research and program development. The increasing interactivity of the Internet, known as ‘Web 2.0′, especially the user-driven social networking sites that allow users to share near limitless amounts of personal information with their peers in the network, is compounding the potential of the Internet as an environment for both STI risk and prevention.

Related:

• Health Risk Behaviors on MySpace
• You’ve Got Mail

Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV infects and kills a type of immune system cell called CD4+ T lymphocytes. These cells are needed to maintain a vigorous immune response, so people infected with HIV eventually become susceptible to other infections and develop full blown AIDS. However, early during HIV infection, other parts of the immune system attempt to fight off the virus. Soon after infection, immune system cells called B lymphocytes begin to produce HIV-specific antibodies (proteins that recognize viral molecules called antigens). The first antibodies to HIV usually appear two to seven weeks after infection; from about 12 weeks after infection, antibodies are made that can kill the specific HIV type responsible for the infection (neutralizing antibodies).

Unfortunately, by this time, it is too late for the antibody (‘‘humoral’’) immune response to clear HIV from the body. Indeed, the humoral immune response to HIV is very slow; for most viruses, neutralizing antibodies appear within days of infection. To help them design an effective HIV vaccine, scientists need to understand how the virus delays humoral responses to HIV infection (and how it later causes the production of HIVspecific antibodies to decline). Little is known, however, about the early effects of HIV infection on B lymphocytes. These cells are born and mature in the bone marrow. ‘‘Naive’’ B lymphocytes, each of which carries an antigen-specific receptor (a protein that binds to a specific antigen), then enter the blood and circulate around the body, passing through the ‘‘peripheral lymphoid organs’’. Exposure to antigens in these organs, which include lymph nodes and gut-associated lymphoid tissues, activates the subset of B lymphocytes that recognize the specific antigens that are present. Finally, with the help of activated T lymphocytes, the activated B lymphocytes proliferate and change (differentiate) into antibody-secreting cells and memory B lymphocytes (which respond more quickly to antigen than naive B lymphocytes). In this study, the researchers investigate the effects of early HIV-1 infection on B lymphocytes in blood and in gut-associated lymphoid tissues.

Although the depletion of gut-associated CD4+ T lymphocytes in early HIV-1 infection is well known, these new results demonstrate the effects of early HIV-1 infection on gut-associated and circulating B lymphocytes. The results of this study are limited by the methods used to analyze the antibodies induced by HIV infection and by only taking tissue samples from one region of the gut. Nevertheless, the findings of polyclonal B-cell activation and damage to gut-associated lymphoid follicles soon after HIV-1 infection may have implications for HIV-1 vaccine design. Specifically, these findings suggest that an effective HIV-1 vaccine will need to ensure that significant levels of neutralizing antibodies are present in people before HIV-1 infection and that other protective immune defenses are fully primed so that, in the event of HIV-1 infection, the virus can be dealt with effectively before it disables any part of the immune system.

Polyclonal B Cell Differentiation and Loss of Gastrointestinal Tract Germinal Centers in the Earliest Stages of HIV-1 Infection. PLoS Med 6(7): e1000107. doi:10.1371/journal.pmed.1000107
The antibody response to HIV-1 does not appear in the plasma until approximately 2–5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1–specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4+ T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells. In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT) B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI) included not only HIV-1–specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1–induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer’s patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis. Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1–induced antibody responses and the delay in plasma antibody responses to HIV-1.

Related:

• Antibodies against persistent viruses
• Re-awakening old genes to help in the fight against viruses
• HIV is evolving rapidly to escape the immune system

A recent article in New Scientist entitled Why microbes are smarter than you thought looks at six behaviours that seem remarkably intelligent for single celled organisms. Single-celled organisms don’t have nervous systems, let alone brains, but they could be viewed as “biological computers” with internal machinery that can process and respond to information.

On MicrobiologyBytes I’ve often discussed bacterial communication – the ways in which bacteria talk to each other using chemical signals. If Bacillus subtilis cells are growing in a nutrient-poor area, they release chemicals into their surroundings which tell their neighbours “There’s not much food here, so clear off or we’ll both starve.” In response to these chemical messages, the other bacteria move away, changing the shape of the colony.

Many single-celled organisms can work out how many other bacteria of their own species are in their vicinity – something known as “quorum sensing“. Each individual bacterium releases a small amount of a chemical into the surrounding medium. If there are lots of other bacteria around, all releasing the same chemical, levels can reach a critical point and trigger a change in behaviour of the whole population. This “voting system” can be used to decide when to launch an attack on a host. Once they have grown to sufficient numbers to overwhelm the immune system, they collectively launch an assault on the body. Jamming these signals might provide us with a way to fight back.

Bacteria form communities known as biofilms, familiar as the thin layer of slime that coats the insides of water pipes, or surgical implants. Many different species live side by side in these “bacterial cities”, consuming each other’s wastes, cooperating to exploit food sources, and safeguarding one another from external threats such as antibiotics.

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Many microbes can accelerate the rate at which their genes mutate. This allows them to obtain new abilities that may be helpful when conditions get tough. Escherichia coli mutates more rapidly when under stress (Stress-induced mutagenesis in bacteria. Science. 2003 300(5624): 1404-9), and yeast can perform the same trick (Adaptive mutation in Saccharomyces cerevisiae. Crit Rev Biochem Mol Biol. 2007 42(4): 285-31).

Microbes are also pretty good at navigation. The single-celled algae Chlamydomonas swim towards light, but only if it is of a wavelength that they can use for photosynthesis. Some bacteria move according to the presence of chemicals in their environment – a behaviour called chemotaxis. Another group of bacteria align themselves to the Earth’s magnetic field, allowing them to head directly north or south, and more importantly, up or down for optimum photosynthesis.

When the amoeba Dictyostelium searches the surface of a Petri dish for food, it makes frequent turns. But it does not do so randomly. If it has just turned right, it is twice as likely to turn left as right on its next turn, and vice versa. It remembers which direction it last turned.

Remarkable though these behaviours are, we have probably only scratched the surface of what single-celled organisms can do. With so many still entirely unknown to science, there must be plenty more surprises in store.

Related:

• Quorum Sensing
• Biofilms
• It’s good to talk
• Communication, cooperation, competition and cheating – bacteria are just like us

Heme is ubiquitous, abundant, and vitally necessary as a cofactor in oxidoreduction and gas transport. Most microorganisms display a complete heme biosynthetic pathway, but are able to acquire the essential ferrous iron from exogenous heme. Free heme or heme arising from hemoproteins is internalized intact and subsequently degraded in the cytosol. Diverse mechanisms for heme uptake have been identified in bacteria. They involve extracellular hemoproteins (hemophores) that capture heme and deliver it to bacteria and cell surface receptors that bind heme, hemoproteins, and/or hemophores. Surface receptors of Gram-positive bacteria are cell-wall anchored proteins that scavenge heme and relay it to specific ABC transporters involved in heme internalization. The absence of these newly identified mechanisms from higher eukaryotic organisms makes them potential targets for new antibacterial drugs, especially since there is growing evidence that heme utilization systems are required for bacterial virulence.

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact. PNAS USA June 29, 2009, doi: 10.1073/pnas.0903842106
Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme.

Related:

• Iron Uptake and Virulence
• New drug targets for urinary tract bacterial infections
• Bacillus anthracis gets iron from hemoglobin
• Utilization of iron by Campylobacter jejuni
• Bacterial sensors of oxygen

New mass sequencing techniques are revealing that the diversity of viruses is much greater than ever imagined. In this article in Microbiology Today (pdf) Peter Simmonds shows that some recent “new” viruses are providing clues to how viruses evolve:

One of the immediate problems facing evolutionary studies of viruses is the evident fact that viruses are hugely diverse in size, appearance, even the nature of their genetic material (DNA or RNA). From this, it is reasonably clear that they are a not a single evolutionary group, and cannot be easily added as a single unit to the tree of life with its three main divisions (Bacteria, Archaea and Eukarya). By the same token, it seems likely that different virus groups (e.g. animal RNA viruses, retroviruses, large DNA viruses, bacteriophages) may indeed have entirely separate evolutionary origins. In this article I will describe two areas where recent discoveries have produced tantalizing new insights into the origin and ubiquity of some of these groups. Through the application of new, mass-sequencing techniques and scope for large-scale environmental sampling for virus genomic sequences, we may finally be able to understand the extent and complexity of the “virosphere” in which we live, and the extraordinary diversity of viruses that infect us.

Read more

Related:

• Evolutionary history and phylogeography of human viruses
• One virus particle can be enough to cause infection
• Coevolution with viruses drives bacterial mutations

Nontyphoidal Salmonellae are responsible for an estimated 1.4 million cases of gastrointestinal disease with 500 associated deaths in the United States, at a cost of $2 billion. The number of cases worldwide probably exceeds 100 million each year. Infection generally occurs after the ingestion of contaminated food or water, and usually leads to a self-limiting enterocolitis. The disease is characterized by diarrhea, abdominal cramps, nausea, fever, vomiting, and headache lasting 7–10 days, followed by a longer period of subclinical fecal shedding. Infants, the elderly, and immunocompromised individuals are at risk for serious systemic complications and death as a result of infection.

Contaminated foods, including beef, pork, poultry, and egg products are frequent vectors responsible for the transmission of these organisms to humans. Livestock can harbor Salmonellae subclinically resulting in carcass contamination at slaughter and in the laying of contaminated eggs. In recent years, as the traditional routes of infection are better controlled, large outbreaks of nontyphoidal Salmonella infection in the United States have been attributed to fruits, vegetables, and processed foods including jalapeño peppers, cantaloupe, cereal, and peanut butter (CDC).

Serology based on surface antigens is the standard method of classification of Salmonella. The host-range and disease can differ considerably between serovars, making such classification important. Throughout the world, the most prevalent nontyphoidal serovars isolated from human sources are serovars Typhimurium and Enteritidis and these two serovars comprise nearly 40% of isolations from human sources in the United States. These serovars can be harbored subclinically in livestock for prolonged periods of time and are thus very difficult to eradicate in the absence of a detailed knowledge of the biology of the organism in this niche.

The bacterial factors necessary for Salmonellae to persist subclinically in the gastrointestinal tract of livestock and to survive and grow in other reservoirs such as crops and processed foods are only beginning to be elucidated. This knowledge will allow the development of new strategies and the identification of points in the production chain where producers can intervene to improve the safety of foods. We review the current status as well as the uses of complete genome sequence information for Salmonellae, and enhancements of genetic techniques that may rapidly increase our knowledge of the biology of this organism in these important food safety niches.

Complete genome sequencing of Salmonellae is allowing us to better understand their genetic diversity, to develop novel tools, and to improve existing genetic techniques to understand the complex biology of these important food-borne pathogens. Approximately half of the genes in Salmonella still have no known phenotype in the environment. Frontiers for further study of Salmonella for improved food safety using modern genetic tools are likely to include determination of the genes necessary for environments where Salmonella must survive outside the host, such as in feces, soil, water, and plants. Understanding how Salmonella completes its entire host-to-host life cycle in agriculture may reveal previously unknown vulnerabilities that will be susceptible to novel intervention and allow us to break the chain of transmission.

Novel genetic tools for studying food-borne Salmonella. Curr Opin Biotechnol. 2009 Apr;20(2):149-57.
Nontyphoidal Salmonellae are highly prevalent food-borne pathogens. High-throughput sequencing of Salmonella genomes is expanding our knowledge of the evolution of serovars and epidemic isolates. Genome sequences have also allowed the creation of complete microarrays. Microarrays have improved the throughput of in vivo expression technology (IVET) used to uncover promoters active during infection. In another method, signature tagged mutagenesis (STM), pools of mutants are subjected to selection. Changes in the population are monitored on a microarray, revealing genes under selection. Complete genome sequences permit the construction of pools of targeted in-frame deletions that have improved STM by minimizing the number of clones and the polarity of each mutant. Together, genome sequences and the continuing development of new tools for functional genomics will drive a revolution in the understanding of Salmonellae in many different niches that are critical for food safety.

Related:

• MicrobiologyBytes: Salmonella
• You are what you eat – but what are you eating?
• Pathogens in raw foods