MicrobiologyBytes

I’ve been very busy over the last few weeks, mostly going to and talking at a whole series of conferences, but also not writing Principles of Molecular Virology (too busy), and spending lots of time sitting in hospitals waiting to get my antibiotic fix for an annoying eye infection. As a result, MicrobiologyBytes has been a bit lightweight recently, and I apologize.

But now it’s time to get going again! I really appreciated the feedback from everyone who contributed to yesterday’s post, and I’ve got a few good ideas I’d like to try out over the next few weeks – make sure you tell me what you think of them when I roll them out. Most importantly, from tomorrow, we’ll be back on a regular schedule with all the microbiology you can take! Stick around and keep commenting :-)

Thanks to everyone who left a comment on yesterday’s post. If you’d like to contribute, there’s still time, and I don’t mind if you prefer to remain anonymous.

Tomorrow, we’ll get back to some microbiology :-)

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To reach the central nervous system (CNS), pathogens have to circumvent the wall of tightly sealed endothelial cells that compose the blood–brain barrier. Neuronal projections that connect to peripheral cells and organs are the Achilles heels in CNS isolation. Some viruses and bacterial toxins interact with membrane receptors that are present at nerve terminals to enter the axoplasm. Pathogens can then be mistaken for cargo and recruit trafficking components, allowing them to undergo long-range axonal transport to neuronal cell bodies. This review highlights the strategies used by pathogens to exploit axonal transport during CNS invasion.

A hitchhiker’s guide to the nervous system: the complex journey of viruses and toxins. 2010 Nature Reviews Microbiology 8: 645-655 doi:10.1038/nrmicro2395

Related:

• Bacterial toxins

Travelers’ diarrhea is one of the most common illnesses affecting those who cross international borders for holiday, visiting family and friends, business, service work, or education. The World Tourism Organization estimates that nearly 1 billion people travel each year; travelers’ diarrhea will affect 20–60% of those who visit low-income countries. Because millions of travelers will be affected by travelers’ diarrhea, with many experiencing disruption to their planned activities and the potential loss of their investment in the trip, there has been much interest in the prevention and treatment of this common condition over the last five decades. Much of the evidence for the clinical description and management of travelers’ diarrhea was generated years ago, however, there is new information on geographic and host risk, etiology, and prevention strategies.

Travel to South Asia, followed by sub-Saharan Africa and South America, carries the highest risk for diarrheal syndromes in returned travelers. Women are more susceptible to travel-related diarrhea than men. Host genetic studies have demonstrated that single nucleotide polymorphisms in the lactoferrin, osteoprotegerin, and IL-10 genes are associated with small but increased risks for diarrhea and enteric pathogens. Enterotoxigenic Bacteroides fragilis is likely to be a new agent identified as causing travelers’ diarrhea, and heat-stable toxin-producing Escherichia coli appears to be more common than heat-labile toxin E. coli. Overall levels of sanitation at the travel destination, including individual eating establishments, are strong predictors for acquisition of travelers’ diarrhea. A new transdermal LT vaccine shows promise in modifying the severity of travelers’ diarrhea. It remains uncertain whether prophylaxis or prompt self-treatment of travelers’ diarrhea will prevent late-onset irritable bowel syndrome. For self-treatment, azithromycin is the drug of choice in travelers to areas where there is a high risk of fluoroquinolone-resistant Campylobacter spp., such as South and Southeast Asia and possibly North Africa, Central and South America.

There is increased understanding of the determinants of travelers’ diarrhea. Despite this travelers’ diarrhea remains one of the most common illnesses in travelers. Continued focus on intervention strategies may ultimately lead to decreased incidence.

Travelers’ diarrhea. Curr Opin Infect Dis. Jul 29 2010

Related:

• Viruses causing childhood diarrhoea in the developing world
• Metagenomic Analysis of Human Diarrhoea

The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. This paper describes the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.

The biofilm matrix. 2010 Nature Reviews Microbiology 8: 623-633 doi:10.1038/nrmicro2415

Related:

• Can filamentous fungi form biofilms?
• Bugs Against Biofilms
• Biofilms Use Chemical Weapons

Infection with influenza virus affects a substantial proportion of the worldwide population each year. In 2009, the perceived global threat of influenza reached an exceptional level after the emergence of a novel swine-origin influenza A H1N1 (so-called swine flu), which was first isolated in local outbreaks in Mexico, Canada, and the USA. The subsequent rapid global spread of this strain and concerns about its possible virulence led national and global health authorities to initiate countermeasures in early 2009, by means of mass immunisation programmes in several countries, including the USA and countries of the European Union. These vaccination campaigns were the cornerstone of public health measures to prevent the undesired consequences of a pandemic. They also served as a reminder (at least to the neurological community) of the 1976 national influenza immunisation programme against swine flu subtype A/NJ/76 in the USA, which was stopped because of the emergence of Guillain-Barré syndrome (GBS) in vaccine recipients.

GBS after vaccination is rare, and most studies have concluded that it is a chance event except in the 1976 programme. However, the small size of vaccine safety trials before licensing, the testing and licensing of vaccines for potential pandemic diseases before the start of the pandemic (so-called mock-up licensing), and the very low incidence of GBS mean that data could be insufficient to assess the risk reliably. Conventional vaccine safety monitoring after licensing does not entirely eradicate this concern.

By contrast with vaccination, evidence is increasing that influenza infection and influenza-like illnesses can act as triggers for GBS. This important fact, which has been highlighted in epidemiological studies, and seems to be underappreciated in public and professional advisory interpretations of influenza vaccine adverse event data and subsequent risk–benefit assessments. The establishment of background rates for GBS will be very useful in this regard; this information has already been provided for several countries.

In addition to the prevention of multiple non-neurological diseases by influenza vaccination, awareness and correct interpretation of all available data about the relation of GBS, influenza infection, and influenza vaccination are a prerequisite for an objective risk–benefit analysis of current and future influenza vaccination campaigns. This paper reviews the existing data derived from studies about GBS after influenza infection and GBS after exposure to influenza vaccine and summarises current information about the plausibility of influenza immunisation as a biological cause of GBS.

Guillain-Barré syndrome after exposure to influenza virus. Lancet Infectious Diseases (2010) 10(9) 643- 651 doi:10.1016/S1473-3099(10)70140-7
Guillain-Barré syndrome (GBS) is an acute, acquired, monophasic autoimmune disorder of peripheral nerves that develops in susceptible individuals after infection and, in rare cases, after immunisation. Exposure to influenza via infection or vaccination has been associated with GBS. We review the relation between GBS and these routes of exposure. Epidemiological studies have shown that, except for the 1976 US national immunisation programme against swine-origin influenza A H1N1 subtype A/NJ/76, influenza vaccine has probably not caused GBS or, if it has, rates have been extremely low (less than one case per million vaccine recipients). By contrast, influenza-like illnesses seem to be relevant triggering events for GBS. The concerns about the risk of inducing GBS in mass immunisation programmes against H1N1 2009 do not, therefore, seem justified by the available epidemiological data. However, the experiences from the 1976 swine flu vaccination programme emphasise the importance for active and passive surveillance to monitor vaccine safety.

Related:

• Fact Sheet on Guillain-Barré syndrome
• MicrobiologyBytes: Influenza
• Campylobacter jejuni

Bacterial virulence results from the interaction between bacteria and their hosts. This interaction provides selection pressure for bacterial adaptation towards increased fitness or virulence. Basic mechanisms involved in bacterial adaptation at the genetic level are point mutations and recombination. As bacterial genome plasticity is higher in vivo than in vitro, host-pathogen interaction may facilitate bacterial adaptation. Comparative genomics has so far been almost entirely focused on genomic changes upon prolonged bacterial growth in vitro.

To achieve a better comprehension of bacterial genome plasticity and the capacity to adapt in response to their host, researchers studied bacterial genome evolution in vivo. They analyzed the impact of individual hosts on genome-wide bacterial adaptation under controlled conditions, by administration of an asymptomatic E. coli isolate to several hosts. Interestingly, the different hosts appeared to personalize their microflora. Adaptation at the genomic level included point mutations in several metabolic and virulence-related genes, often affecting pleiotropic regulators, but re-isolates from each patient showed a distinct pattern of genetic alterations in addition to random changes. These results provide new insights into bacterial traits under selection during E. coli in vivo growth, further explaining the mechanisms of bacterial adaptation to specific host environments.

Host Imprints on Bacterial Genomes – Rapid, Divergent Evolution in Individual Patients. (2010) PLoS Pathog 6(8): e1001078. doi:10.1371/journal.ppat.1001078
Bacterial virulence results from the interaction between bacteria and their hosts. This interaction provides selection pressure for bacterial adaptation towards increased fitness or virulence. Basic mechanisms involved in bacterial adaptation at the genetic level are point mutations and recombination. As bacterial genome plasticity is higher in vivo than in vitro, host-pathogen interaction may facilitate bacterial adaptation. Comparative genomics has so far been almost entirely focused on genomic changes upon prolonged bacterial growth in vitro. To achieve a better comprehension of bacterial genome plasticity and the capacity to adapt in response to their host, we studied bacterial genome evolution in vivo. We analyzed the impact of individual hosts on genome-wide bacterial adaptation under controlled conditions, by administration of asymptomatic bacteriuria E. coli isolate 83972 to several hosts. Interestingly, the different hosts appeared to personalize their microflora. Adaptation at the genomic level included point mutations in several metabolic and virulence-related genes, often affecting pleiotropic regulators, but re-isolates from each patient showed a distinct pattern of genetic alterations in addition to random changes. Our results provide new insights into bacterial traits under selection during E. coli in vivo growth, further explaining the mechanisms of bacterial adaptation to specific host environments.

Related:

• The long now – 40,000 generations of E. coli
• Spread of Pathogenicity Islands in Escherichia coli
• The continuing evolution of E. coli O157:H7

Human adenoviruses (HAdV) are non-enveloped double-stranded DNA (dsDNA) viruses associated with acute infections. Although these infections are generally self-limiting, the re-emergence of certain HAdV types has also been linked to potentially fatal respiratory infections in both civilian and military populations. In addition to their disease associations, replication-defective or conditionally replicating HAdVs continue to be evaluated in ~25% of approved phase I to III clinical trials for vaccine and therapeutic gene transfer. However, the lack of accurate details of the virus structure limits the reengineering of HAdV vectors and prevents a better understanding of the virus life cycle. High-resolution HAdV structure determination presents a challenge because of the large size (910 Å average diameter, 150 megadalton) and complexity (pseudo-T = 25) of the virus.

After more than a decade of research, scientists have pieced together the structure of a human adenovirus – the largest complex ever determined at atomic resolution. The new findings about the virus, which causes respiratory, eye, and gastrointestinal infections, may lead to more effective gene therapy and to new anti-viral drugs.

Crystal Structure of Human Adenovirus at 3.5 Å Resolution. (2010) Science 329(5995): 107 -1075 doi: 10.1126/science.1187292
Rational development of adenovirus vectors for therapeutic gene transfer is hampered by the lack of accurate structural information. Here, we report the x-ray structure at 3.5 angstrom resolution of the 150-megadalton adenovirus capsid containing nearly 1 million amino acids. We describe interactions between the major capsid protein (hexon) and several accessory molecules that stabilize the capsid. The virus structure also reveals an altered association between the penton base and the trimeric fiber protein, perhaps reflecting an early event in cell entry. The high-resolution structure provides a substantial advance toward understanding the assembly and cell entry mechanisms of a large double-stranded DNA virus and provides new opportunities for improving adenovirus-mediated gene transfer.

Related:

• Adenovirus vectors – new genes, new vaccines
• MicroRNA regulation of tumor-killing viruses