Walking with bacteria

They swim, they swarm, they twitch and glide…they even ride on comet tails, and now it seems that bacteria can ‘walk’ as Maxsim Gibiansky and colleagues demonstrate in their short but sweet research published in Science.

Gibiansky et al. studied the behaviour of Pseudomonas aeruginosa, a bacteria that is ordinarily found in soil and water, but has increasingly been associated with opportunistic infections in humans (and is a particular problem in those with cystic fibrosis). A key feature of P. aeruginosa is that these bacteria form multicellular, surface-bound communities called biofilms and are able to move within these communities by twitching motility owing to their type IV pili (hair-like structures on bacteria that can extend, tether to a surface and then retract to move bacteria along). The researchers studied microscopy movies of the P. aeruginosa biofilms and used computer software to track how the bacteria transitioned from planktonic state (that is, freely suspended in liquid) to the surface-bound biofilm.

Two different surface motility mechanisms were observed just after P. aeruginosa bacteria attached to a surface, but before a microcolony of bacteria were formed. The scientists studied mutant bacteria lacking flagella (a tail-like bacterial appendage that can also enable bacteria to move) that can only move using their type IV pili. These bacteria tended to ‘crawl’ in one direction when positioned horizontal to the surface and ‘walked’ in all directions when attached vertically to the surface by one end of the bacteria. Each movement mechanism was useful for surface exploration; crawling enabled directional movement across larger areas (6 μm distance) than walking, which enabled rapid exploration in local areas (up to 2 μm distance). Furthermore, these same movements were observed in wild-type bacteria. Moreover, the orientation of bacteria influenced biofilm morphology. Surface detachment was facilitated by type IV pili by tilting bacteria from horizontal to vertical positions and after bacterial division newborn bacteria detach and then ‘walk’ away. Finally, bacteria lacking type IV pili could neither ‘crawl’ or ‘walk’.

Scientific observations like this brevia report add to the understanding of bacterial behaviour in biofilms and could eventually lead to useful, new treatments against biofilm-forming pathogens.


ResearchBlogging.orgGibiansky, M., Conrad, J., Jin, F., Gordon, V., Motto, D., Mathewson, M., Stopka, W., Zelasko, D., Shrout, J., & Wong, G. (2010). Bacteria Use Type IV Pili to Walk Upright and Detach from Surfaces Science, 330 (6001), 197-197 DOI: 10.1126/science.1194238


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Altruistic bacterial charity workers help protect their vulnerable stressed out kin

US scientists have found that a small minority of highly antibiotic-resistant bacteria will produce and share a molecule, indole, that can activate survival mechanisms in less-resistant cells to enable the whole bacterial population to survive stressful environments despite the fact that production of this signalling molecule weakens the fitness of bacteria.

The increasing incidence of antibiotic resistance and the emergence of so-called ‘superbugs’ are of huge importance to medicine and society as a whole with the ever-increasing likelihood of a return to a world without antibiotics. This potentially disastrous public health crisis led the Infectious Diseases Society of America to launch the “10x’20” initiative in which they call for a global commitment to research and develop 10 new, effective antibiotic drugs by 2020. As a complement to this drug development, research into how bacteria develop this resistance could provide crucial clues for the rational design of new antimicrobial agents.

Henry Lee and colleagues investigated the population dynamics of antibiotic resistance. They grew a vat of E. coli with increasing amounts of the antibiotic norfloxacin and then took samples of the bacteria and monitored the percentage of bacteria that became resistant to the antibiotic. The scientists found an individual isolate that was highly resistant to norfloxacin (even higher than the greatest norfloxacin levels tested in their bioreactor). These bacteria produced indole, which is known to aid tolerance to stress in E. coliindole induces anti-stress mechanisms such as drug efflux pumps that help drive out toxic substances from the bacterial cell—although its production can reduce the overall fitness of the bacteria. Moreover, indole boosts the antibiotic resistance of the whole bacterial population and not just the select few that produce it. This population-based resistance was not drug specific and was even observed when the scientists challenged E. coli with gentamicin, which is a different type of antibiotic (with a different mode of action) to the quinolone norfloxacin.

The researchers conclude that under antibiotic stress, a few drug-resistant mutants will endure a fitness cost to produce and share the benefits of the metabolite indole to “shield the less-resistant bacteria from antibiotic insult” and enable these ‘weak’ bacteria to survive.

ResearchBlogging.orgLee HH, Molla MN, Cantor CR, & Collins JJ (2010). Bacterial charity work leads to population-wide resistance. Nature, 467 (7311), 82-5 PMID: 20811456

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Monkeypox infections on the increase in Africa

The incidence of a smallpox-like disease—caused by the monkeypox virus—has increased 20-fold in the Demoncratic Republic of Congo (DRC) over the past 30 years, according to new research published online in the journal PNAS. The findings suggest that, as smallpox vaccination programmes ceased in the DRC in 1980, people are now immunologically ‘naïve’ to orthopoxviruses (including monkeypox and smallpox viruses) and could be at an increased risk of infection by this family of viruses.

The monkeypox virus can cause a serious zoonotic disease (potentially transmitted to humans from rodent species such as squirrels as well as primates such as monkeys) that is similar to smallpox. Smallpox vaccinations not only helped eradicate the smallpox virus, but also provided cross-protective immunity to monkeypox virus infection.

Anne Rimoin and colleagues assessed the burden of human monkeypox in the DRC by analyzing surveillance data for this disease from 2005–2007 in regions known to be endemic for the virus, a feat which had not been conducted since the early 1980s. In their up-to-date surveillance data across nine health zones in central DRC, 760 human monkeypox cases were confirmed by laboratory tests and the researchers found that the average annual cumulative incidence of monkeypox virus infection was 5.53 cases per 10,000 people across all zones. Men, children under the age of 15 years and people living in forested areas or who had not received a prior smallpox vaccination were at an increased risk of monkeypox infection whilst those who had been vaccinated against smallpox had a 5.2-fold lower risk of infection by the monkeypox virus than unvaccinated individuals. Rimoin et al. then compared the 1980s active surveillance data with their new 2000s findings from the same health zone and found that the incidence of human monkeypox in this zone increased substantially from 0.72 cases per 10,000 people in the 1980s to 14.42 cases per 10,000 people between 2005 and 2007.

The investigators add that “entire households are now mostly or completely [smallpox] vaccine naive”, which could result in increased human-human transmission between different generations within the same house. Furthermore, Rimoin and colleagues argue that because of several limitations (including poor access to remote areas) their study could have under-reported the true incidence of human monkeypox and the observed dramatic increase in disease incidence could in fact be a “conservative estimate”. Improved and continued disease surveillance will be needed to assess the true burden of monkeypox virus infection on public health in African populations, and could aid the development and implementation of strategies to reduce the risk of monkeypox virus infection.

ResearchBlogging.orgAnne W. Rimoin, Prime M. Mulembakani, Sara C. Johnston, James O. Lloyd Smith, Neville K. Kisalu, Timothee L. Kinkela, Seth Blumberg, Henri A. Thomassen, Brian L. Pike, Joseph N. Fair, Nathan D. Wolfe, Robert L. Shongo, Barney S. Graham, Pierre Formenty, E, & Major (2010). Major increase in human monkeypox incidence
30 years after smallpox vaccination campaigns
cease in the Democratic Republic of Congo Proceedings of the National Academy of Sciences USA (Published ahead of print 30th August 2010) DOI: 10.1073/pnas.1005769107

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Racial background affects risk of severe sepsis

High infection rates and increased risk of acute organ dysfunction in black individuals explains why people from this racial background are more likely to have (and die from) severe sepsis than white individuals, according to a new study published in JAMA.

Severe sepsis (when the body has a systemic inflammatory response to infection that can lead to multiple organ failure and death) is well-known to be more frequent in black individuals than white people. However, just why the incidence of severe sepsis is higher in this racial group is unknown and it is particularly important to investigate whether these racial disparities are because of different susceptibilities to infection or organ failure—a critical distinction that could influence treatment. High infection rates can be combated with vaccination programmes in at-risk individuals whilst high incidence rates of organ failure can be improved with better care in hospitals.

In what can only be described as a mammoth retrospective study (that included data from all hospitalisations across seven US states, that is, a potential total number of over 63 million people in the study), Florian B. Mayr and colleagues wanted to examine exactly why black people have a higher incidence of severe sepsis than white people.

The researchers found that of more than 8.6 million hospital admissions (not related to childbirth) in black and white individuals, over 2.2 million of the cases were because of infection and 381,787 of these cases (67,812 black patients; 313,975 white patients) had severe sepsis. They found that black patients had 67% higher hospitalization rates (after standardising for both age and sex) because of severe sepsis than did white patients. Furthermore, black patients also had both increased infection rates, risk of developing organ dysfunction and mortality compared with white patients. Differences in infection-related hospitalisations between the races were especially pronounced in younger adults (20–65 years old).

Findings from this large, retrospective cohort study clearly demonstrate that high severe sepsis rates in black people are because of a “higher likelihood of being hospitalised with infection and a higher risk of developing acute organ dysfunction”. These results have implications for public health; interventions to reduce infection (such as vaccinations) and better quality of care and management of hospitalised patients should be promoted, especially in healthcare providers that serve black communities. Furthermore, more research is needed to investigate risk of severe sepsis in people from other racial groups.

ResearchBlogging.orgMayr, F., Yende, S., Linde-Zwirble, W., Peck-Palmer, O., Barnato, A., Weissfeld, L., & Angus, D. (2010). Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis JAMA: The Journal of the American Medical Association, 303 (24), 2495-2503 DOI: 10.1001/jama.2010.851

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A little incentive goes a long way when it comes to vaccine uptake

Offering people free lentils and metal food dishes substantially improves the number of young children that receive a full course of childhood immunisations in resource poor areas, and is more cost effective than just improving the vaccine services available in the region, according to a new study published free in the British Medical Journal.

Abhijit Vinayak Banerjee and colleagues wanted to assess how effective non-financial incentives—1 kg raw lentils per vaccine and a set of metal thali plates once a child has received all their immunisations—and increased availability of vaccine services were at improving immunisation rates in young children in rural Rajasthan, India. Their study included 1,640 children (aged 1–3 years) from 134 villages who were randomly assigned to three groups:

–          the ‘immunisation camp’ who received reliable, monthly vaccinations from healthcare professionals

–          the ‘immunisation plus camp’ who in addition to reliable, monthly vaccines were also offered cheap little extras of free lentils (costing about $1) for every vaccine and a set of thalis (a snip at $1.50) for a complete set of vaccines (BCG, diphtheria-pertussis, tetanus, polio and measles) received by the children

–          a control group who did not receive any interventions

Taken from Banerjee, A. V. et al. BMJ 2010;340:c2220

The researchers showed that immunisation rates were higher in the children that were offered reliable immunisations plus a little extra (39%) compared with the rates in children who were just offered the reliable immunisations (16%). Interestingly, children in districts neighbouring the immunisation plus camp also had bigger improvements in immunisation rates than those living near the immunisation camp villages. Not only that, these small incentives were cost effective (costing an estimated $17.35 per fully immunised child in camps with incentives compared with $25.18 per fully immunised child in camps without these extras).

The findings from this study by Banerjee et al. could have important implications for vaccine policies. Moreover, the authors question whether offering lentils can even be considered a “cost” as they clearly will have immediate, nutritional benefits to both the vaccinated children and their families.

ResearchBlogging.orgBanerjee, A., Duflo, E., Glennerster, R., & Kothari, D. (2010). Improving immunisation coverage in rural India: clustered randomised controlled evaluation of immunisation campaigns with and without incentives BMJ, 340 (may17 1) DOI: 10.1136/bmj.c2220

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IL-33—a new treatment against sepsis?

New research shows that the novel cytokine interleukin (IL)-33 reduces sepsis and has “therapeutic potential” to treat this often fatal inflammatory condition. According to the study published this week in Nature Medicine, IL-33 promotes neutrophil recruitment to the site of infection, which is a critical host defence response, and the levels of the decoy IL-33 receptor soluble ST2 in serum could affect whether people recover from sepsis.

Sepsis is a serious illness in which the body has a massive inflammatory response to an infection. Severe sepsis and septic shock can affect multiple organs in the body including the heart, lungs, liver and brain, and is life-threatening (30–50% of people with severe sepsis or septic shock die) and requires treatment in intensive care.

Jose Alves-Filho and colleagues used experimental models of sepsis (using cecal ligation and puncture or CLP) to investigate the role of IL-33 during sepsis. The scientists induced sepsis in mice and then treated them with recombinant IL-33; IL-33-treated mice had a marked reduction in mortality compared to untreated controls and IL-33 protected mice from sepsis for 3h after CLP. The researchers found that IL-33 treatment increased the number of neutrophils migrating to the site of infection (by increasing the expression of the chemokine receptor that is crucial for neutrophil recruitment, CXCR2). This neutrophil recruitment promoted clearance of the bacterial infection and IL-33 also reduced the systemic proinflammatory cytokines (e.g. IL-6, tumour necrosis factor α and CXCL2) that occurred in response to the infective bacteria. Furthermore, the scientists analysed blood serum from healthy individuals and people who had sepsis. They found that people with sepsis had higher levels of IL-33 than healthy people, and that serum levels of soluble ST2 (the decoy receptor of IL-33) were substantially higher in people who did not survive sepsis compared to those who recovered from the disease (soluble ST2 serum levels were negligible in healthy individuals).

The research reveals a “previously unknown mechanism of action of IL-33” and further studies will show whether IL-33 could be used as a potentially novel therapy for sepsis.

ResearchBlogging.orgAlves-Filho, J., Sônego, F., Souto, F., Freitas, A., Verri, W., Auxiliadora-Martins, M., Basile-Filho, A., McKenzie, A., Xu, D., Cunha, F., & Liew, F. (2010). Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection Nature Medicine DOI: 10.1038/nm.2156

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Scientists find protein involved in OCD development

The protein Slitrk5—which is specific to neurons—is involved in the pathogenesis of obsessive–compulsive disorder (OCD) and loss of this protein leads to OCD-like behaviour in mice. The study, published in Nature Medicine, demonstrates that Slitrk5-knockout mice can be used as model of OCD and could help elucidate the molecular mechanisms that underlie this condition.

OCD is an anxiety disorder characterised by repetitive and obtrusive thoughts; this obsession leads to compulsive behaviour (e.g. handwashing or hoarding), which sufferers hopes will relieve their anxiety. Genetic analysis in humans has linked the gene SLITRK1 to Tourette’s syndrome—an OCD-like disorder—but the pathogenesis and genetics of OCD remain poorly understood.

Sergey Shmelkov and colleagues hypothesised that SLITRK5 (part of the same gene family as SLITRK1) could be involved in OCD-like behaviour and so they engineered a knockout mouse which lacked Slitrk5. The scientists observed that the Slitrk5-/- mice developed an anxiety-like behaviour and obsessively groomed, these mice had severe skin lesions and loss of facial hair that was not seen in wild-type mice. They found that fluoxetine—a selective serotonin reuptake inhibitor used in the treatment of OCD and also depression—relieved the compulsive behaviour in Slitkr5-knockout mice. The researchers then used anatomical, histological and functional analysis of the brains of Slitrk5-/- mice to further characterise their animal model of OCD. They recorded a number of observations in mice that lacked Slitkr5 compared to their wild-type counterparts: increased striatal volume, increased neural activity in the orbitofrontal cortex, abnormalities and changes to cell morphology in the striatum, decreased expression of glutamate receptors, and dysregulation of the corticostriatal circuitry.

Shmelkov et al. conclude that “Slitrk5 may have a central role in the development of OCD-like behaviour”. Some of the findings in this study are supported by existing data in humans (e.g. imaging studies imply that people with OCD have disruptions in corticostrial neurotransmission) but as yet no association with SLITRK5 has been found in humans. The investigators hope that their disease model of OCD can help investigate the pathogenesis and etiology of this prevalent anxiety disorder.

ResearchBlogging.orgShmelkov, S., Hormigo, A., Jing, D., Proenca, C., Bath, K., Milde, T., Shmelkov, E., Kushner, J., Baljevic, M., Dincheva, I., Murphy, A., Valenzuela, D., Gale, N., Yancopoulos, G., Ninan, I., Lee, F., & Rafii, S. (2010). Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive–like behaviors in mice Nature Medicine DOI: 10.1038/nm.2125

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