MicrobiologyBytes

The eradication of vaccine-preventable infectious diseases remains an important public health priority. To achieve this goal, the level of immunity afforded needs to be high and long-lasting. For whooping cough (pertussis), one of the leading causes of mortality in infants, immunity has been shown to wane in some individuals. The epidemiological impacts of this observation depend critically on the duration of protective immunity in the entire population, which remains notoriously difficult to estimate. Immunity to whooping cough lasts at least 30 years on average, much longer than previously thought, according to a new study. Once thought to be under control following widespread childhood vaccination, whooping cough has been on the rise since the 1980s in the United States and other countries. Several explanations have been proposed for the surprising increase in cases, and one leading idea is that the immunity enjoyed by vaccinated or previously exposed people is waning. It has been documented that, in some individuals, immunity has waned over time, but details of how long protection typically lasts and how its waning affects disease transmission have not been clear.

To try to answer these questions, researchers used mathematical models to explore various scenarios and compared the predictions generated by those models to data on whooping cough incidence. They constructed two different models based on assumptions of the effects of pertussis exposure on a person whose immunity has lapsed  and that person’s relative contribution to transmission. Then they compared the models’ predictions to whooping cough incidence data from England and Wales from both the pre-vaccine era (1945-1957) and the vaccine era (1958-1972). In particular, they looked for matches in two key measures: the number of years between big outbreaks and the frequency of “extinctions” – periods of time when no whooping cough cases were reported in the population.

The analysis revealed that, on average, whooping cough immunity lasts at least 30 years and perhaps as long as 70 years after natural infection. This is surprising because clinical epidemiologists currently believe the duration of pertussis immunity is somewhere between four and 20 years. In addition, repeat infections appear to contribute relatively little to the transmission cycle. And when people whose immunity has waned are re-exposed to whooping cough, they rarely become infected. In fact, their immunity to the disease may be boosted by re-exposure. Still, the researchers are cautious about drawing conclusions about current day vaccination practices from their study of historical data. It is worth pointing out that in the past 20 years or so, the nature of the vaccines that have been used has changed quite fundamentally. The data used in the study are from a time when a whole-cell vaccine was in use; now an acellular vaccine, which stimulates a different part of the immune system, is typically used, especially in North America.

Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures. PLoS Pathog 5(10): e1000647 doi:10.1371/journal.ppat.1000647
Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.

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• Vaccination is up to 99% effective
• Vaccine to prevent urinary tract infections shows promise
• New Insights Could Lead to a Better Pneumococcal Vaccine

Insects are the most abundant and diverse animal class on earth, and they are associated with an amazing variety of symbiotic microorganisms. In fact, mutualistic bacteria probably constitute a key factor for the enormous success of insects in adapting to novel environments and food sources. Several insect taxa completely depend on their mutualistic bacteria for successful growth and reproduction, and the nutrients that are provided by the bacteria have been elucidated in some cases by physiological and/or genomic studies. These nutritional interactions have been the focus of considerable attention, and it is generally assumed that the advantage for the insect in most insect–bacteria symbioses is the supply with nutrients. Recently, however, an increasing number of studies indicate that another type of symbiotic associations can play an equally crucial role: the protection of the insect host or its nutritional resources against pathogens, parasitoids or predators by symbiotic microorganisms. Interestingly, a specific group of bacteria is involved in approximately half of the described defensive symbioses: the high-GC Gram-positive actinobacteria. Why are members of this group so common as defensive mutualists in insects, while they are only very rarely found to be involved in nutritional symbioses? This article argues that actinobacteria are predisposed towards engaging in defensive rather than nutritional interactions owing to their ecological and physiological prerequisites, in particular their ability to exploit a wide range of nutrient sources and their extraordinary potential to produce secondary metabolites with antibiotic properties. A comparison of defensive insect–actinobacteria symbioses known to date yields interesting insights into the conditions under which such associations evolve and points to future directions for research on other insect taxa that might be protected by microorganisms.

Mutualistic microorganisms are well known to play a key role in providing nutrients for successful growth and reproduction in many insects. Several recent studies indicate that they can be equally important for the protection of the host and its nutritional resources against pathogen attack. In particular, different actinobacteria have been found to defend ants, beetles and wasps against detrimental microorganisms by producing antibiotics. The extraordinary abilities of actinobacteria to exploit a wide variety of carbon and nitrogen sources and their extensive repertoire of secondary metabolites probably predispose this group to engage in protective symbioses. Defensive mutualisms with actinobacteria might constitute a general and widespread theme in the ecology and evolution of arthropods, and the study of the secondary metabolites involved promises to uncover novel drug candidates for human medicine.

Actinobacteria as mutualists: general healthcare for insects? Trends Microbiol. Oct 21 2009

Related:

• The weird and wonderful actinobacteria
• An introduction to the actinobacteria

Dengue virus infection usually causes a severe flu like illness, although symptoms may be mild in young children. DHF, however, is a severe and sometimes fatal complication of dengue virus infection that affects about half a million people every year after infection with any one of the four dengue virus (DENV) serotypes. DHF patients usually fall into two groups; children and adults who become infected with a second dengue virus serotype after an initial primary dengue virus infection with a different serotype, and infants with primary dengue virus infections born to mothers who have some dengue virus immunity. The widely accepted explanation for the pathogenesis of DHF in these settings, particularly during infancy, is antibody-dependent enhancement (ADE) of DENV infection.

Researchers conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and enhancing capacities at the time of DENV3 infection and development of infant DHF. The study examined 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity and measurable DENV3 ADE activity. The infants who developed DHF did not have significantly higher frequencies or levels of DENV3 ADE activity compared to symptomatic infants without DHF. A higher weight-for-age in the first 3 mo of life and at illness presentation was associated with a greater risk for DHF from a primary DENV infection during infancy. This prospective nested case-control study of primarily DENV3 infections during infancy has shown that infants exhibit a full range of disease severity after primary DENV infections.

The current model for development of DHF in infants around 6 months old is that anti-dengue virus antibodies transferred from a dengue-immune mother to her child somehow enhance dengue virus infection, resulting in more severe symptoms (the  antibody-dependent enhancement  model). These results support an initial in vivo protective role for maternally derived antibody. There was no significant association between DENV3 ADE activity at illness onset and the development of DHF compared with less severe symptomatic illness. The results of this study should encourage rethinking or refinement of the current ADE pathogenesis model for infant DHF and stimulate new directions of research into mechanisms responsible for the development of DHF during infancy.

A Prospective Nested Case-Control Study of Dengue in Infants: Rethinking and Refining the Antibody-Dependent Enhancement Dengue Hemorrhagic Fever Model. PLoS Med 6(10): e1000171 doi:10.1371/journal.pmed.1000171

Related:

• Dengue Virus
• Dengue virus infection activates the unfolded protein response
• Pathogenic Flaviviruses

The Public Library of Science has published The Genomics of Emerging Infectious Disease, a collection of essays, perspectives, and reviews that explores how genomics – with all its associated tools and techniques – can provide insights into our understanding of emerging infectious disease. As pandemic H1N1 2009 influenza (swine flu) continues to spread around the globe, people want to know if this virus poses more of a threat than other seasonal flu strains, how fast it is spreading (and where), and what can be done to contain it. The increasing speed at which complete genome sequences and other genome-scale data can be generated provides tremendous opportunities to address these questions by identifying the molecular changes in disease agents such as influenza viruses that will enable us to track their spread and evolution and to generate the vaccines and drugs necessary to combat them.  The Genomics of Emerging Infectious Disease collection discusses the challenges involved and how scientists and public health professionals might take advantage of these opportunities and advances to prevent the next pandemic.

Emerging infectious diseases are caused by a wide range of organisms, but they are perhaps best typified by zoonotic viral diseases, which cross from animal to human hosts and can have a devastating impact on human health. These zoonotic diseases include monkeypox, Hendra virus, Nipah virus, and severe acute respiratory syndrome coronavirus (SARS-CoV), in addition to influenza A and the lentiviruses (HIV) that cause AIDS.  The apparent increased transmission of pathogens from animals to humans over recent decades can be attributed to the unintended consequences of globalization as well as environmental factors and changes in agricultural practices. Articles in the collection also shine a spotlight on specific pathogens, some familiar and widespread, such as influenza A virus, some “re-emerging”, such as the Mycobacterium tuberculosis complex that causes tuberculosis, and some identified only relatively recently, such as the bacterium Helicobacter pylori, which is associated with peptic ulcers and gastric cancer. Others discuss the broader implications of genomics research in this area, such as what it means for researchers in developing countries or for our biosecurity. Genomics can and should be used proactively to build our preparedness for and responsiveness to biological threats:

• Editorial: Eisen J, MacCallum CJ (2009) Genomics of Emerging Infectious Disease: A PLoS Collection. PLoS Biol 7(10): e1000224
• Coloma J, Harris E (2009) Molecular Genomic Approaches to Infectious Diseases in Resource-Limited Settings. PLoS Med 6(10): e1000142
• Can an Infectious Disease Genomics Project Predict and Prevent the Next Pandemic? PLoS Biol 7(10): e1000219
• The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats. PLoS Biol 7(10): e1000217
• Discovering the Phylodynamics of RNA Viruses. PLoS Comput Biol 5(10): e1000505
• Computational Resources in Infectious Disease: Limitations and Challenges. PLoS Comput Biol 5(10): e1000481
• The Role of Medical Structural Genomics in Discovering New Drugs for Infectious Diseases. PLoS Comput Biol 5(10): e1000530
• The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases. PLoS Genet 5(10): e1000612
• Toward the Use of Genomics to Study Microevolutionary Change in Bacteria. PLoS Genet 5(10): e1000627
• The Application of Genomics to Emerging Zoonotic Viral Diseases. PLoS Pathog 5(10): e1000557
• The Role of Genomics in Tracking theEvolution of Influenza A Virus. PLoS Pathog 5(10): e1000566
• The Past and Future of Tuberculosis Research. PLoS Pathog 5(10): e1000600
• Helicobacter pylori’s Unconventional Role in Health and Disease. PLoS Pathog 5(10): e1000544
• Helminth Genomics: The Implications for Human Health. PLoS Negl Trop Dis 3(10): e538

In mammals, adenosine assumes an essential role in regulating innate and acquired immune responses. Strong or excessive host inflammatory responses, e.g. in response to bacterial infection, exacerbate the tissue damage inflicted by invading pathogens. Successful immune clearance of microbes therefore involves the balancing of pro- and anti-inflammatory mediators. The cytokines IL-4, IL-10, IL-13, and TGF-β play a role in restricting excessive inflammation, but only adenosine is able to completely suppress immune responses. The immunoregulatory attributes of adenosine are mediated via four transmembrane adenosine receptors: A1, A2A, A2B, and A3. T lymphocytes express the high affinity A2A receptor as well as the low affinity A2B receptor. Depending on their activation state, macrophages and neutrophils express all four adenosine receptors, whereas B cells harbor only A2A. Engagement of A2A inhibits IL-12 production, increases IL-10 in monocytes and dendritic cells, and decreases cytotoxic attributes and chemokine production in neutrophils. Generation of adenosine at sites of inflammation, hypoxia, organ injury, and traumatic shock is mediated by two sequential enzymes.

Although extracellular adenosine is essential for the suppression of inflammation, build-up of excess adenosine is also detrimental. This is exemplified in patients with a deficiency in adenosine deaminase, an enzyme that converts adenosine to inosine. Adenosine deaminase deficiency causes severe compromised immunodeficiency syndrome, with impaired cellular immunity and severely decreased production of immunoglobulins. As the regulation of extracellular adenosine is critical in maintaining immune homeostasis, perturbation of adenosine levels is likely to affect host immune responses during infection.

Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. Scientists examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall–anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen Bacillus anthracis, and adenosine synthesis also enabled escape of B. anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses.

Staphylococcus aureus synthesizes adenosine to escape host immune responses. J. Exp. Med. 28 Sep 2009 doi:10.1084/jem.20090097

Related:
Staphylococcus aureus: superbug
Evolution and pathogenesis of Staphylococcus aureus

Chronic hepatitis B virus (HBV) infection affects about 400 million people around the globe, being one of the most common infectious diseases and among the world’s leading causes of death. Antiviral therapy of chronic hepatitis B (CHB) aims to improve quality of life and survival chance of the patients by preventing progression of liver damage to cirrhosis, end-stage liver disease and liver cancer (HCC), thus preventing anticipated liver-related death. This goal is achieved by suppression of HBV replication in a sustained or maintained manner, either by short-term “curative” treatment with standard (IFN) and pegylated interferon (Peg-IFN) or long-term “suppressive” therapy with nucleos(t)ide analogues, like lamivudine, adefovir, entecavir, telbivudine and tenofovir. Since both strategies have advantages and disadvantages, the wise treatment of a patient with CHB requires careful balance between prediction of the natural history of HBV and of the potential benefit of anti- HBV therapy. Recent data on the long-term efficacy of third generation of nucleos(t)ide analogues entecavir and tenofovir have tipped the balance towards long-term suppression therapy as the first-line option for most patients with CHB, independent of the HBeAg status.

Chronic hepatitis C is a major worldwide health problem with an estimated prevalence of 1.6-2%. In Europe, more than 9 million chronic carriers and approximately 86,000 deaths per year are estimated due to the late complications of hepatitis C virus (HCV). The prognosis of chronic hepatitis C depends on the rate of fibrosis progression, which over a 20-30 year time span, may determine the risk of developing cirrhosis and its complications, namely HCC, liver decompensation, hepatic encephalopathy and oesophageal variceal bleeding. The only therapeutic intervention able to halt this progressive process is eradication of HCV by Interferon (IFN)-based therapies. Since the empirical choice to use IFN in 1986, therapy for chronic hepatitis C has constantly evolved over the past decade, with the attainable sustained virological response (SVR) rates increasing through the years. The addition of the guanosine nucleoside analogue ribavirin (Rbv) to IFN can be considered the major breakthrough in the treatment of chronic hepatitis C. Through mechanisms of action that still remain largely unknown, Rbv has determined a greater number of patients to ultimately achieve a SVR by increasing the rates of on-treatment response and reducing the rates of post-treatment relapse. In the large phase III clinical trials designed to assess its efficacy and safety, the combination of IFN and Rbv resulted in SVR rates of 30-35% in HCV genotype 1 patients and 75-80% in HCV-2 and 3 patients. These figures exceeded by far those obtained by IFN monotherapy, effectively leading the way for combination therapy to become the standard of care in the late 1990’s. The latest innovation in the treatment of chronic hepatitis C has been the pegylation of the IFN molecule (PegIFN) through the attachment of one or more polyethylene glycols to the IFN, a process that is able to modify the immunological, pharmacokinetic and pharmacodynamic properties of the drug. Standard IFN was in fact characterized by a number of limitations, such as poor stability, short elimination half-life and potential immunogenicity, that ultimately determined its small antiviral effect. Moreover, due to the increase in elimination half-life obtained by the pegylation process, it has been possible to lengthen the dosing interval from the unpractical three times a week schedule required by standard IFN, to the more “user friendly” once a week administration, a feature that has increased convenience whilst facilitating adherence to the recommended treatment schedule. Following the demonstration of a more potent antiviral effect in terms of SVR rates in phase III randomized trials, PegIFN has become the standard of care for chronic hepatitis C.

One year of interferon therapy inhibits HBV replication in one third of the patients whereas long-term administration of oral nucleos(t)ide analogues is efficient in most of them, as long as early treatment adaptation in patients with partial virological response and resistance is provided. Following the demonstration of a more potent antiviral effect in terms of sustained virological response (SVR) rates, Pegylated-IFN coupled with Ribavirin has become the standard treatment for chronic hepatitis C, with nearly 65% of all treated patients achieving a SVR. Long-term suppression of HBV and eradication of HCV would halt the progression of chronic hepatitis to cirrhosis, hepatocellular carcinoma and liver decompensation.

HBV and HCV Therapy. Viruses 2009, 1(3), 484-509. doi:10.3390/v1030484

Related:

• Hepatitis B and C viruses
• Hepatitis C Virus: a mountain to climb
• Does the outcome of HCV infection vary with the infecting virus type?
• Plugging the holes in hepatitis C virus antiviral therapy

In the past few decades our fundamental understanding of how microorganisms grow and survive in natural settings or in host tissues has changed considerably. It is now widely accepted that microbes in nature rarely survive as solitary cells, but rather grow as biofilms. In fact, the formation of biofilms is so prevalent that it is likely to be a positively selected trait that became fixed very early in microbial evolution as an important feature for survival on surfaces in diverse or changing environments.

A biofilm can be described as a microbially derived sessile community characterized by cells that are irreversibly attached to a substratum or interface or to each other, are embedded in a matrix of extracellular polymeric substances that they have produced, and exhibit an altered phenotype with respect to growth rate and gene transcription. It is important to note that not all researchers apply the term biofilm synonymously. For example, another widely accepted biofilm definition describes a “microscopic mushroom-shaped” 3D community of microbial cells held in association and firmly attached to surfaces via an extracellular polymeric matrix that is permeated by water channels allowing efficient biomass exchange between the population and the environment. This definition encompasses many examples of biofilm structures in aqueous environments, but does not include surface-associated microbial growth in environments that are not saturated in water or fluid. The range of physical or environmental conditions necessary for the formation of biofilm structures is a debated topic. For example, surface-associated microbial growth in low water environments, such as on rocks, rhizospheres or the surfaces of buildings, have been termed unsaturated, terrestrial or subaerial biofilms by some authors. As a result of these diverse definitions, differences exist in the application of the terminology to various microbial assemblages, and it is unclear whether all assemblages qualify as biofilms versus aggregates, microbial mats, flocs or microcolonies.

In a broad context, biofilm formation involves genetically programmed changes in the organization and metabolism of the solitary or planktonic forms of microorganisms. Structurally, cells leave a motile, solitary or planktonic condition and become securely attached to a surface and/or other cells within an exopolymeric matrix. The structure of individual cells is not significantly altered, but the individuals become organized into a communal structure, encased in slime, and display novel characteristics and phenotypes. One frequently measurable change in the phenotype of cells in a biofilm, as compared to their planktonic counterparts, is significantly increased tolerance to chemical, biological or physical stresses. In fact, one of the most striking and consistently reported features of microbial populations growing as biofilms is their increased intrinsic resistance to antimicrobial agents. As a result, conventional antibiotic agents and biocides often fail to eradicate infectious microorganisms from hosts or from inert hard surfaces when present in a biofilm.

It is generally assumed that filamentous fungi, some of which have a significant impact on our health or our economy, do not form biofilms. In contrast to this assumption, this paper discusses recent findings supporting the hypothesis that surface-associated filamentous fungi can form biofilms. Based on these findings and on previous models for bacterial and yeast systems, it proposes preliminary criteria and a model for biofilm formation by filamentous fungi.

Can filamentous fungi form biofilms? Trends Microbiol. Oct 13 2009

Related:

• Candida parapsilosis secreted lipase is a major virulence factor
• Bugs Against Biofilms
• Who you gonna call? Slimebusters!

Retroviruses package two copies of full-length RNA in one virus particle (virion). One of the consequences of packaging two RNAs is frequent recombination during DNA synthesis when reverse transcriptase uses parts of both RNAs as templates. Although frequent recombination can occur during DNA synthesis of all virions, a genotypically different recombinant can only be generated from virions that package two different RNAs (heterozygous virions). High genetic diversity of HIV-1 presents a difficult barrier for drug treatment and vaccine development.

Using a recombination assay, researchers have shown that RNA molecules derived from two similar HIV-1 proviruses can randomly assort and be efficiently copackaged into virions. However, heterozygous virions are formed less efficiently when the two proviruses contain variations in their dimerization initiation signal (DIS). Located at the loop of stem-loop 1 of the 5′ untranslated region, the DIS is a 6-nt palindromic sequence that forms the initial interaction between the two HIV-1 RNAs. The Gag polyproteins of HIV-1 interact with, and specifically package, the viral RNA to generate infectious viruses. We have previously examined whether RNA dimerization occurs prior to virus assembly using HIV-1 variants with DIS mutations that abolish their palindromic nature (for example, from GCGCGC to GGGGGG) but can form perfect base pairs with the DIS of a partner virus (such as a virus with CCCCCC at the DIS). In the coinfected cells if dimeric RNAs are packaged, then the GGGGGG viral RNA would preferentially pair with CCCCCC viral RNA, and an increase in the formation of heterozygous virions would be observed. In contrast, if two monomeric RNAs are packaged, then there would not be an increase in heterozygous viruses. Results reveal that most of the virions from coinfected cells were heterozygous, indicating that copackaged RNA partner selection, i.e. dimerization, occurs prior to the packaging of virion RNA.

HIV-1 full-length RNAs serve at least two functions: as a template for Gag/Gag-Pol translation, and as genetic material packaged in the virion. Many cellular factors ensure the correct macromolecular trafficking between nucleus and cytoplasm; specifically, mechanisms exist to prevent the export of intron-containing transcripts, such as the full-length HIV-1 RNA. Most cellular mRNAs are fully spliced before export and many are believed to exit the nucleus via the NXF1-dependent pathway. However, many proteins and some RNAs use an alternative, CRM-1-dependent pathway to migrate out of the nucleus. The extent to which these two pathways are linked or overlap is currently unknown, and the reason for their differential use is subject to speculation.

Once transcribed, the nascent full-length RNA of HIV-1 must travel to the appropriate host cell sites to be translated or to find a partner RNA for copackaging to form newly generated viruses. In this report, scientists sought to identify the location where HIV-1 RNA initiates dimerization and the influence of the RNA transport pathway used by the virus on downstream events essential to viral replication. Using a cell-fusion-dependent recombination assay, they were able to demonstrate that the two RNAs destined for copackaging into the same virion select each other mostly within the cytoplasm. Moreover, by manipulating the RNA export element in the viral genome, they showed that the export pathway taken is important for the ability of RNA molecules derived from two viruses to interact and be copackaged. These results further illustrate that at the point of dimerization the two main cellular export pathways are partially distinct. Lastly, by providing Gag in trans, they demonstrated that Gag is able to package RNA from either export pathway, irrespective of the transport pathway used by the gag mRNA. These findings provide unique insights into the process of RNA export in general, and more specifically, of HIV-1 genomic RNA trafficking.

Probing the HIV-1 Genomic RNA Trafficking Pathway and Dimerization by Genetic Recombination and Single Virion Analyses. 2009 PLoS Pathog 5(10): e1000627 doi:10.1371/journal.ppat.1000627

Related:

• The shape of HIV RNA
• Studying the structure of HIV

The life of a bacterial cell is feast or famine. To survive the bacterium must rapidly adapt to changing environmental conditions. Colonization of the mammalian gut provides an enteric organism with an abundant source of carbohydrates, whereas a flash flood instantly depletes the nutrient supply for a soil bacterium. Nutrient-rich conditions lead to a decrease in mass doubling time and an increase in cell size, whereas nutrient-poor conditions curtail growth and reduce cell size. Changes in growth rate must be accompanied by changes in the cell cycle to ensure that cell division stays coordinated with mass doubling, chromosome replication and chromosome segregation. How organisms adjust their cell cycle dynamics to compensate for changes in nutritional conditions is an important outstanding question in bacterial physiology. Recent work suggests that multiple signalling pathways transmit nutritional and growth rate information directly to the cell cycle machinery. Multiple signalling pathways permit cells to constantly sample their environments and fine-tune cell cycle processes, a substantial advantage under challenging conditions.

Adaptation to fluctuations in nutrient availability is a fact of life for single-celled organisms in the ‘wild’. A decade ago our understanding of how bacteria adjust cell cycle parameters to accommodate changes in nutrient availability stemmed almost entirely from elegant physiological studies completed in the 1960s. This article summarizes recent groundbreaking work in this area and discuss potential mechanisms by which nutrient availability and metabolic status are coordinated with cell growth, chromosome replication and cell division.

Metabolism, cell growth and the bacterial cell cycle. Nature Reviews Microbiology 7, 822 (2009)

Related:

• Bacterial Chemoreceptors
• A day in the life of a cyanobacterium
• How smart are bacteria?