Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram-negative bacillus discovered at the beginning of the 1980s that causes gastritis, peptic ulcers and stomach cancer in humans. So what’s new?
Helicobacter pylori infection: what’s new. Current Opinion in Infectious Diseases, 25(3): 337–344 Helicobacter pylori colonizes the human stomach causing gastritis and severe diseases including gastric cancer. One of the most dangerous H. pylori factors, CagA, has been investigated in relation to gastric cancer: recently this relationship was strongly reinforced by the finding that CagA interacts with the tumor suppressor apoptosis-stimulating protein of p53-2 (ASPP2), promoting p53 degradation. Treg have been proposed to be involved in H. pylori infection and gastric disease: recent findings suggest that Treg-induced tolerance, rather than immunity to H. pylori, may result in less severe disease. The eradication rates achieved with the standard triple therapy dropped below 80%, mainly due to antibiotic resistance, while no vaccines are currently licensed; new treatments/regimens were subjected to clinical trials, in some cases strongly increasing the eradication rates.
One in six cancers – two million a year globally – are caused by largely treatable or preventable infections. Makes you think, doesn’t it?
Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology, 9 May 2012, doi:10.1016/S1470-2045(12)70137-7
Background: Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.
Methods: We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.
Findings: Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.
Interpretation: Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.
Julian Davies presents the SGM Prize Medal Lecture ‘Molecules, Microbes and Me’ on 26 March at the Society for General Microbiology’s Spring Conference 2012 in Dublin.
It seems to be turning into nanotechnology week on MicrobiologyBytes :-)
Nanotechnology and the Treatment of HIV Infection. (2012) Viruses 2012, 4(4), 488-520; doi:10.3390/v4040488
Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. The emerging field of nanotechnology may play an important role in addressing these challenges by creating drugs that possess pharmacological advantages arising out of unique phenomena that occur at the “nano” scale. At these dimensions, particles have physicochemical properties that are distinct from those of bulk materials or single molecules or atoms. In this review, basic concepts and terms in nanotechnology are defined, and examples are provided of how nanopharmaceuticals such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles, nanocarriers, micelles, liposomes and dendrimers have been investigated as potential anti-HIV therapies. Such drugs may, for example, be used to optimize the pharmacological characteristics of known antiretrovirals, deliver anti-HIV nucleic acids into infected cells or achieve targeted delivery of antivirals to the immune system, brain or latent reservoirs. Also, nanopharmaceuticals themselves may possess anti-HIV activity. However several hurdles remain, including toxicity, unwanted biological interactions and the difficulty and cost of large-scale synthesis of nanopharmaceuticals.
Ah, nanotechnology – the great salvation of humankind that will cure cancer, solve the energy crisis and provide for our eco-friendly manufacturing future. That’s assuming that we can figure out how to build the nanomachines we need of course. Which is where this comes in:
“The swimming of the marine cyanobacterium Synechococcus has been a longstanding puzzle. Synechococcus is ubiquitous in the euphotic zone of the worlds oceans making it a major primary producer. Approximately one third of the open ocean isolates are motile. It moves through seawater at speeds of 5 to 25 m/s while rotating about its long axis at about 1 Hz. It accomplishes this despite the complete absence of any observable motile apparatus such as flagella. A clue to Synechococcus’s propulsion comes from a bacterium that does not swim, but glides on surfaces…”
On the Mysterious Propulsion of Synechococcus. (2012) PLoS ONE 7(5): e36081. doi:10.1371/journal.pone.0036081
We propose a model for the self-propulsion of the marine bacterium Synechococcus utilizing a continuous looped helical track analogous to that found in Myxobacteria. In our model cargo-carrying protein motors, driven by proton-motive force, move along a continuous looped helical track. The movement of the cargo creates surface distortions in the form of small amplitude traveling ridges along the S-layer above the helical track. The resulting fluid motion adjacent to the helical ribbon provides the propulsive thrust. A variation on the helical rotor model allows the motors to be anchored to the peptidoglycan layer, where they drive rotation of the track creating traveling helical waves along the S-layer. We derive expressions relating the swimming speed to the amplitude, wavelength, and velocity of the surface waves induced by the helical rotor, and show that they fall in reasonable ranges to explain the velocity and rotation rate of swimming Synechococcus.
I promised I would write about the first Microbiology Twitter Journal Club (#microtwjc), held yesterday, so here it is. Click through the images below for larger versions. As ever, I am grateful for the invaluable help of Martin Hawksey.
So where do we go from here? Onwards, clearly :-) I’m really looking forward to the next journal club. Stay tuned to #microtwjc for details. It is important that this remains a student-led process, but it would be great to have some more academics contributing (without taking over).
A key aspect for success is choosing the right paper, which needs to be interesting, high quality, but with enough uncertainly to promote discussion. The danger is burnout for the organizers, who are also busy doing lots of other things. It’s up to the community to help out by suggesting suitable papers for discussion via the hashtag so that all the burden of organizing doesn’t fall on a few people.
Should authors be invited to take part? I see no harm in this as long as they are given adequate notice, although I suspect that most will not want to. The other option is to try to invite one or two subject “experts” for each paper.
I’m sure other people will have further suggestions, so let’s hear them. We’re off to a great start!
Bacterial cell shape is dictated by the composition of the cell envelope component peptidoglycan. Some important pathogens have a characteristic helical corkscrew morphology that may help them burrow into mucus overlaying cells to initiate colonization and pathogenicity. One example is Campylobacter jejuni, the leading cause of bacterial-induced diarrheal disease in the developed world.
Direct evidence supporting the hypothesis that C. jejuni shape is related to its pathogenicity traits has not previously been provided. Researchers have identified a gene encoding a peptidase modifying peptidoglycan that is essential for maintaining the C. jejuni corkscrew shape. We can now connect a C. jejuni gene with morphology and peptidoglycan biosynthesis. Loss of this gene was also found to affect pathogenic attributes such as chicken colonization, biofilms, motility, and activation of host inflammatory mediators. In addition, this is the first study to thoroughly characterize C. jejuni peptidoglycan structure and to identify a gene involved in peptidoglycan maintenance.
These findings highlight an emerging theme in bacterial pathogenesis research: the connection between bacterial cell biology and pathogenesis. Finally, characterization of C. jejuni cell shape and peptidoglycan provides a starting point for further work in this area in C. jejuni and other bacteria with curved and helical morphologies.
Peptidoglycan-Modifying Enzyme Pgp1 Is Required for Helical Cell Shape and Pathogenicity Traits in Campylobacter jejuni. (2012) PLoS Pathog 8(3): e1002602. doi:10.1371/journal.ppat.1002602
The impact of bacterial morphology on virulence and transmission attributes of pathogens is poorly understood. The prevalent enteric pathogen Campylobacter jejuni displays a helical shape postulated as important for colonization and host interactions. However, this had not previously been demonstrated experimentally. C. jejuni is thus a good organism for exploring the role of factors modulating helical morphology on pathogenesis. We identified an uncharacterized gene, designated pgp1 (peptidoglycan peptidase 1), in a calcofluor white-based screen to explore cell envelope properties important for C. jejuni virulence and stress survival. Bioinformatics showed that Pgp1 is conserved primarily in curved and helical bacteria. Deletion of pgp1 resulted in a striking, rod-shaped morphology, making pgp1 the first C. jejuni gene shown to be involved in maintenance of C. jejuni cell shape. Pgp1 contributes to key pathogenic and cell envelope phenotypes. In comparison to wild type, the rod-shaped pgp1 mutant was deficient in chick colonization by over three orders of magnitude and elicited enhanced secretion of the chemokine IL-8 in epithelial cell infections. Both the pgp1 mutant and a pgp1 overexpressing strain – which similarly produced straight or kinked cells – exhibited biofilm and motility defects. Detailed peptidoglycan analyses via HPLC and mass spectrometry, as well as Pgp1 enzyme assays, confirmed Pgp1 as a novel peptidoglycan DL-carboxypeptidase cleaving monomeric tripeptides to dipeptides. Peptidoglycan from the pgp1 mutant activated the host cell receptor Nod1 to a greater extent than did that of wild type. This work provides the first link between a C. jejuni gene and morphology, peptidoglycan biosynthesis, and key host- and transmission-related characteristics.
Don’t understand how cell shape can affect pathogenesis? Neither do I! That’s why I’ll be at #microtwjc at 8pm UK time tonight!
Yuan Chang & Patrick Moore present the Marjory Stephenson Prize Lecture ‘Old themes and new variations in human tumour virology’ on 27 March at the Society for General Microbiology’s Spring Conference 2012 in Dublin.
A new online microbiology journal club will take place on alternate Tuesdays at 8pm UK Time (GMT+1) and aims to cover topics across the whole spectrum of microbiology. The first paper (for 8th May) is:
Peptidoglycan-Modifying Enzyme Pgp1 Is Required for Helical Cell Shape and Pathogenicity Traits in Campylobacter jejuni. (2012) PLoS Pathog 8(3): e1002602.
“Bacterial cell shape is dictated by the composition of the cell envelope component peptidoglycan. Some important pathogens have a characteristic helical corkscrew morphology that may help them burrow into mucus overlaying cells to initiate colonization and pathogenicity. One example is Campylobacter jejuni, the leading cause of bacterial-induced diarrheal disease in the developed world. Direct evidence supporting the hypothesis that C. jejuni shape is related to its pathogenicity traits has not previously been provided. We identified a gene encoding a peptidase modifying peptidoglycan that is essential for maintaining the C. jejuni corkscrew shape. We can now connect a C. jejuni gene with morphology and peptidoglycan biosynthesis. Loss of this gene was also found to affect pathogenic attributes such as chicken colonization, biofilms, motility, and activation of host inflammatory mediators. In addition, this is the first study to thoroughly characterize C. jejuni peptidoglycan structure and to identify a gene involved in peptidoglycan maintenance. Our findings highlight an emerging theme in bacterial pathogenesis research: the connection between bacterial cell biology and pathogenesis. Finally, our characterization of C. jejuni cell shape and peptidoglycan provides a starting point for further work in this area in C. jejuni and other bacteria with curved and helical morphologies.”
“So let us invite ourselves to commit to Open Discourse. Let us set the tone and establish the precedent of enlightened debate that is public spirited, as well as public. Let us refrain from contributing the inconsequential, the self serving and the counterproductive. And above all, let us remember that discourse need not be discourteous. I encourage all of us to not only participate in this movement, but to promote it. Tell a friend. Tell a mentor. Tell a protégé. Start submitting comments. In the end the value we receive will be the value we give. And the value to the world will be greater still.” Beyond open access: open discourse, the next great equalizer. (2006) Retrovirology 2006, 3: 55 doi:10.1186/1742-4690-3-55
Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram-negative bacillus discovered at the beginning of the 1980s that causes gastritis, peptic ulcers and stomach cancer in humans. So what’s new?
