Friday, November 30, 2012

 

Reducing bias in bacterial community analysis of lower respiratory infections.


Reducing bias in bacterial community analysis of lower respiratory infections.


Nov 2012

Source

Molecular Microbiology Research Laboratory, Institute of Pharmaceutical Science, King's College London, London, UK.

Abstract


High-throughput pyrosequencing and quantitative PCR (Q-PCR) analysis offer greatly improved accuracy and depth of characterisation of lower respiratory infections. However, such approaches suffer from an inability to distinguish between DNA derived from viable and non-viable bacteria. This discrimination represents an important step in characterising microbial communities, particularly in contexts with poor clearance of material or high antimicrobial stress, as non-viable bacteria and extracellular DNA can contribute significantly to analyses. Pre-treatment of samples with propidium monoazide (PMA) is an effective approach to non-viable cell exclusion (NVCE). However, the impact of NVCE on microbial community characteristics (abundance, diversity, composition and structure) is not known. Here, adult cystic fibrosis (CF) sputum samples were used as a paradigm. The effects of PMA treatment on CF sputum bacterial community characteristics, as analysed by pyrosequencing and enumeration by species-specific (Pseudomonas aeruginosa) and total bacterial Q-PCR, were assessed. At the local community level, abundances of both total bacteria and of P. aeruginosa were significantly lower in PMA-treated sample portions. Meta-analysis indicated no overall significant differences in diversity; however, PMA treatment resulted in a significant alteration in local community membership in all cases. In contrast, at the metacommunity level, PMA treatment resulted in an increase in community evenness, driven by an increase in diversity, predominately representing rare community members. Importantly, PMA treatment facilitated the detection of both recognised and emerging CF pathogens, significantly influencing 'core' and 'satellite' taxa group membership. Our findings suggest failure to implement NVCE may result in skewed bacterial community analyses.

PubMed

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Friday, November 23, 2012

 

A Case of Steroid-induced Hyperinfective Strongyloidiasis with Bacterial Meningitis.


A Case of Steroid-induced Hyperinfective Strongyloidiasis with Bacterial Meningitis.


Nov 2012
[Article in Korean]

Source

Department of Internal Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 705-718, Korea.

Abstract


Strongyloides stercoralis is a soil transmitted intestinal nematode that is endemic in the tropical and subtropical regions. In most individuals who are infected, chronic, usually asymptomatic, gastrointestinal infection persists. But, in immunocompromized hosts or in patients receiving immunosuppressive therapy, autoinfection of S. stercoralis may result in the dissemination of larvae, leading to fatal hyperinfection and increased rate of complications. We report a case of hyperinfective strongyloidiasis with bacterial meningitis in a patient receiving steroid therapy. Strongyloidiasis was diagnosed by the presence of filariform larvae of S. stercoralis in the bronchoalveolar lavage cytology and upper gastrointestinal endoscopic biopsy specimen. Her clinical symptoms had progressively aggravated and developed bacterial meningitis during treatment. She died despite aggressive antibiotic and antihelminthic therapy.

PubMed

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Saturday, November 17, 2012

 

Real-time PCR as a diagnostic tool for bacterial diseases.


Real-time PCR as a diagnostic tool for bacterial diseases.


2012

Source

Laboratoire de Bactériologie, Département des Agents Infectieux, Institut de Biologie et Pathologie, CHU de Grenoble, Université Joseph Fourier Grenoble 1, France and LAPM, CNRS UMR 5163, Institut Jean Roget, Campus Santé, Université Joseph Fourier-Grenoble 1, France. mmaurin@chu-grenoble.fr.

Abstract


In recent years, quantitative real-time PCR tests have been extensively developed in clinical microbiology laboratories for routine diagnosis of infectious diseases, particularly bacterial diseases. This molecular tool is well-suited for the rapid detection of bacteria directly in clinical specimens, allowing early, sensitive and specific laboratory confirmation of related diseases. It is particularly suitable for the diagnosis of infections caused by fastidious growth species, and the number of these pathogens has increased recently. This method also allows a rapid assessment of the presence of antibiotic resistance genes or gene mutations. 
Although this genetic approach is not always predictive of phenotypic resistances, in specific situations it may help to optimize the therapeutic management of patients. Finally, an approach combining the detection of pathogens, their mechanisms of antibiotic resistance, their virulence factors and bacterial load in clinical samples could lead to profound changes in the care of these infected patients.

PubMed

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A rapid flow cytometric method for distinguishing between febrile bacterial and viral infections.


A rapid flow cytometric method for distinguishing between febrile bacterial and viral infections.


Nov 2012

Source

Department of Biochemistry, University of Turku, Turku, Finland. Electronic address: jarnuu@utu.fi.

Abstract


Antibiotic resistance due to the inappropriate use of antimicrobials is one of the most critical public health problems worldwide. A major factor underlying the unnecessary use of antibiotics is the lack of rapid and accurate diagnostic tests. Therefore, we aimed to develop a novel rapid flow cytometric method for distinguishing between febrile bacterial and viral infections

In this prospective comparative study, quantitative flow cytometric analysis of FcγRII/CD32, CR1/CD35, MHC Class I receptor (MHCI), and C5aR/CD88 on human phagocytes was performed in 286 hospitalized febrile patients with suspected infection. After using microbiological and serological detection methods, or clinical diagnosis, 205 patients were identified with either bacterial (n=136) or viral (n=69) infection. Receptor data from patients were compared to those of 50 healthy controls. We developed a flow cytometric marker of local and systemic bacterial infections designated "bacterial infection score (BIS)" incorporating the quantitative analysis of FcγRII/CD32, CR1/CD35, C5aR/CD88 and MHCI on neutrophils and/or monocytes, which displays 91% sensitivity and 92% specificity in distinguishing between microbiologically confirmed bacterial (n=77) and serologically confirmed viral infections (n=61) within 1hour. 

 The BIS method was effectively applied to distinguish between bacterial and viral (pandemic H1N1 influenza) pneumonia cases with 96% sensitivity and 92% specificity. We propose that the rapid BIS test can assist physicians in deciding whether antibiotic treatment is necessary, thus reducing unnecessary antimicrobial use.

PubMed

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Friday, November 16, 2012

 

The use of antimicrobial-impregnated PMMA to manage periprosthetic infections: controversial issues and the latest developments.


The use of antimicrobial-impregnated PMMA to manage periprosthetic infections: controversial issues and the latest developments.


Nov 2012

Source

Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai - China and Department of Orthopaedic Surgery, Changzhou Wujin Hospital, Jiangsu University School of Medicine, Jiangsu - China.

Abstract


Despite improvements in intraoperative antimicrobial procedures, in surgical techniques and in implant design for joint replacement, periprosthetic infection after arthroplasty is still one of the most challenging problems encountered by orthopedic surgeons. Systemic antibiotics are not sufficiently effective to eradicate such deep infections because of the impaired blood circulation and low antibiotic concentration at the implantation site. As a local drug delivery system, antibiotic-impregnated PMMA (polymethylmethacrylate) bone cements have been widely used for prophylaxis or treatment of deepinfections after total joint replacement. However, the effectiveness of antibiotic-loaded PMMA in preventing infections after arthroplasty is still controversial. Furthermore, the outcomes of established deep infections treated with this technique are not consistent. The local use of antibiotics has led to the emergence of antibiotic-resistant bacterial strains and has adverse effects on the function of osteogenic cells. Recently, many efforts have been made to identify new antibacterial agents that can be loaded into PMMA. These antimicrobial agents should exhibit good antibacterial activity against antibiotic-resistant strains and should simultaneously enhance osteointegration between the PMMA and the bone tissue. PMMA loaded with chitosan or chitosan derivatives has been demonstrated to induce improved osteogenic activity and to exhibit antibacterial activity in a preclinical study.

PubMed

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Reduction in Intraoperative Bacterial Contamination of Peripheral Intravenous Tubing Through the Use of a Passive Catheter Care System.


Reduction in Intraoperative Bacterial Contamination of Peripheral Intravenous Tubing Through the Use of a Passive Catheter Care System.


Nov 2012

Source

From the Departments of *Anesthesiology and Critical Care Medicine, †Anesthesiology, and ‡Pathology, Dartmouth-Hitchcock Medical Center; and §Geisel School of Medicine, the Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire.

Abstract


BACKGROUND: Bacterial contamination of intravascular devices has been associated with increased morbidity and mortality in various hospital settings, including the perioperative environment. Catheter hub disinfection has been shown in an ex vivo model to attenuate intraoperative injection of bacterial organisms originating from the anesthesia provider's hands, providing the impetus for improvement in intraoperative disinfection techniques and compliance. In the current study, we investigated the clinical effectiveness of a new, passive catheter care station in reducing the incidence of bacterial contamination of open lumen patient IV stopcock sets. The secondary aim was to evaluate the impact of this novel intervention on the combined incidence of 30-day postoperative infections and IV catheter-associated phlebitis.

METHODS:Five hundred ninety-four operating room environments were randomized by a computer-generated list to receive either a novel catheter care bundle (HubScrub and DOCit) or standard caps in conjunction with a sterile, conventional open lumen 3-way stopcock set (24 inch with 3-gang 4-way and T-Connector). Patients underwent general anesthesia according to usual practice and were followed prospectively for 30 postoperative days to identify the development of health care-associated infections (HCAIs) and/or phlebitis. The primary outcome was intraoperative bacterial contamination of the primary stopcock set used by the anesthesia provider(s). The secondary outcome was the combined incidence of 30-day postoperative infections and phlebitis.

RESULTS:Five hundred seventy-two operating rooms were included in the final analysis. Study groups were comparable with no significant differences in patient, provider, anesthetic, or procedural characteristics. The catheter care station reduced the incidence of primary stopcock lumen contamination compared with standard caps (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.63-0.98, P = 0.034) and was associated with a reduction in the combined incidence of HCAIs and IV catheter-associated phlebitis with and without adjustment for patient and procedural covariates (OR(adjusted) 0.589, 95% CI 0.353-0.984, P = 0.040). The risk-adjusted number needed to treat to eliminate 1 case of lumen contamination was 9 (95% CI 3.4-13.5) patients, whereas the risk-adjusted number needed to treat to eliminate 1 case of HCAI/catheter-associated phlebitis was 17 (95% CI 11.8-17.9) patients.

CONCLUSION:Intraoperative use of a passive catheter care station significantly reduced open lumen bacterial contamination and the combined incidence of 30-day postoperative infections and phlebitis.

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New Infection, Not Relapse, Brings Back Lyme Symptoms, Study Says


New Infection, Not Relapse, Brings Back Lyme Symptoms, Study Says


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Thursday, November 15, 2012

 

Conquering antibiotic-resistant bacteria by knowing the facts


Conquering antibiotic-resistant bacteria by knowing the facts

The Center for Disease Control and Prevention featured awareness of unnecessary antibiotic use on November 13, 2012 on their website as a kick off to their “Get Smart About Antibiotics Week.” Inappropriate use continues to be a major problem in the U.S. and continues to be problem contributing to antibiotic-resistant bacteria.

Medline Plus presented results of a poll on November 13, 2012 indicating 90 percent of Americans know antibiotics treat bacterial infection, but 36 percent incorrectly think these drugs eradicate viral infections like the flu or common cold. An important factor related to this issue involves antibiotic-resistant superbugs such as methicillin-resistant Staphylococcus aureus (MRSA). About 60,000 people die in the U.S. every year from drug-resistant infections. Taking antibiotics when unnecessary leads to the bacteria becoming resistance to the drug. The bacteria then mutate into superbugs meaning that the microorganism can withstand the effects of the antibiotic. The bacteria lives and needs a stronger antibiotic to kill it. Unfortunately, drug development evolves slowly and individuals die because no drug will kill the stronger bacteria.
Medscape Medical News reported good news on the rate of antibiotic prescriptions in the U.S. decreased 17 percent between 1999 and 2010. However, some states still overprescribe. Seven states in the south prescribing antibiotics more than double the rate of other states in the nation. The seven states in order of most prescriptions of antibiotics filled per 1000 population include Kentucky, West Virginia, Tennessee, Mississippi, Louisiana, Alabama and Arkansas. On the flip side, the states ranked starting with the lowest prescriptions filled include Alaska, Hawaii, California, Oregon, Washington, Colorado and New Hampshire.
According to Science Daily, research shows overuse of antibiotic hastens the development of bacteria resistant to drugs. Antibiotic use began in the 1930s, but bacteria resistance to the antibiotics began in the 1990s. People believed that the drugs worked so well and request their use inappropriate.
What can consumers do to help with the problem of antibiotic overuse? Mayo Clinic gives advice on best actions to take. First, do not demand antibiotics from your healthcare provider. The provider must decide what is best for the patient. Second, do not take antibiotics prescribed for another person. Consuming the wrong medicine can delay appropriate treatment and contribute to bacteria resistant to antibiotics. Third, when antibiotics are prescribed, do not skip doses, do not save any pills for the next time you are sick and take all the pills. Consumers can help with antibiotic use and help solve the problem of bacteria-resistance to antibiotics.
Examiner

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Wednesday, November 14, 2012

 

New Type of Bacterial Protection Found Within Cells


New Type of Bacterial Protection Found Within Cells

UC Irvine biologists have discovered that fats within cells store a class of proteins with potent antibacterial activity, revealing a previously unknown type of immune system response that targets and kills bacterial infections.

Steven Gross, UCI professor of developmental and cell biology, and colleagues identified this novel intercellular role of histone proteins in fruit flies, and it could herald a new approach to fighting bacterial growth within cells. 

The study appears today in eLife, a new peer-reviewed, open-access journal supported by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

“We found that these histone proteins have pan-antibacterial abilities and can have a wide-ranging effect,” Gross says. “If we can discover how to manipulate the system to increase histone levels, we may one day have a new way to treat patients with bad bacterial infections.”

Histones exist in large numbers in most animal cells; their primary job is to help DNA strands fold into compact and robust structures inside the nucleus. Gross said there is some evidence that histones secreted from cells protect against bacteria living outside cells. However, many bacteria enter cells, where they can avoid the immune system and continue replicating.

In principle, Gross says, histones could protect cells against such bacteria from the inside, but for many years this was thought unlikely because most histones are bound to DNA strands in the cell nucleus, whereas bacteria multiply in the cellular fluid outside the nucleus, called cytosol. Additionally, free histones can be extremely damaging to cells, so most species have developed mechanisms to detect and degrade free histones in the cytosol.

In their study, Gross and colleagues demonstrate that histones bound to lipid (fat) droplets can protect cells against bacteria without causing any of the harm normally associated with the presence of free histones. In experiments with lipid droplets purified from Drosophila fruit fly embryos, they show that lipid-bound histones can be released to kill bacteria.

The researchers injected similar numbers of bacteria into Drosophila embryos that contained lipid-bound histones and into embryos genetically modified to not contain them. They discovered that the histone-deficient flies were 14 times more likely to die of bacterial infections. Similar results were found in experiments on adult flies. Additional evidence suggested that histones might also protect mice against bacteria.

“Because numerous studies have now identified histones on lipid droplets in many different cells — from humans as well as  mice and flies — it seems likely that this system may be quite general,” Gross says.

Preetha Anand, Silvia Cermelli, Robilyn Sigua and Lan Huang of UCI; Zhihuan Li and Michael Welte of New York’s University of Rochester; Adam Kassan, Marta Bosch and Albert Pol of the August Pi i Sunyer Biomedical Research Institute in Barcelona, Spain; and Andre Ouellette of USC contributed to the study (Anand et al. eLife 2012;1:e00003. DOI: 10.7554/eLife.00003), which was supported by the National Institutes of Health (grants GM64624 and GM64687), the National Science Foundation and the Spanish Ministry of Science & Innovation.

Infection Control Today

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Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective.


Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective.


Nov 2012

Source

1] Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark. [2].

Abstract


The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonas aeruginosa is commonly isolated from the airways of patients with CF, where it most often establishes chronic infections that usually persist for the rest of the lives of the patients. This bacterium is a major cause of mortality and morbidity and has therefore been studied intensely. Here, we discuss how P. aeruginosa evolves from a state of early, recurrent intermittent colonization of the airways of patients with CF to a chronic infection state, and how this process offers opportunities to study bacterial evolution in natural environments. We believe that such studies are valuable not only for our understanding of bacterial evolution but also for the future development of new therapeutic strategies to treat severe chronic infections.

PubMed

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Cirrhosis, cellulitis and cats: a 'purrfect' combination for life-threatening spontaneous bacterial peritonitis from Pasteurella multocida.


Cirrhosis, cellulitis and cats: a 'purrfect' combination for life-threatening spontaneous bacterial peritonitis from Pasteurella multocida.


Nov 2012

Source

Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia.

Abstract


Pasteurella multocida is a Gram-negative coccobacillus that colonises the upper airways of many animals, in particular, dogs and cats. It acts as an opportunistic infection in humans following an animal bite or scratch and is associated with soft tissue infections, septicaemia and pneumonia, particularly in patients with a compromised immune response, such as patients with liver failure. Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis with a death rate of 10-15%. We report a case of a 47-year-old man with cirrhosis who presented with life-threatening P multocida SBP and bacteraemia secondary to a lick from a cat to a cellulitic leg wound. This case highlights the potential severity of an infection from domestic animals and an otherwise innocuous organism in an immunocompromised host.

PubMed

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Sunday, November 11, 2012

 

Pneumonia number one killer of children

Pneumonia number one killer of children

Muhammad QasimSunday, November 11, 2012 
From Print Edition



Rawalpindi

Pneumonia being the leading cause of death in children kills an estimated 1.4 million children under the age of five every year worldwide. Every year, it accounts for 18 per cent of all deaths of children below five years of age, which is more than AIDS, malaria and tuberculosis combined. Out of these, 99 per cent of deaths occur in developing countries.

In Pakistan, more than 352,000 children die before their fifth birthday every year and almost one third of these deaths are due to pneumonia. If not all, at least 70 per cent of these deaths can be avoided with the help of in time management of the cases. There is a need to create awareness among public that pneumonia can easily be avoided through prevention and it is curable.

Professor and Head of Community Medicine at CMH Lahore Medical College Dr. Muhammad Ashraf Chaudhry expressed this while talking to ‘The News’ in connection with World Pneumonia Day, which is observed every year on November 12 around the globe. The theme of the day this year is: ‘Fight Pneumonia: Save a Child’.

He added that the day is observed with an aim to raise awareness of pneumonia as a public health issue and help prevent millions of avoidable deaths from pneumonia that occur each year. “World Pneumonia Day is an opportunity to remind our leaders that the lives of babies and children are too important to be discounted,” said Dr. Ashraf.

Pneumonia is a form of acute respiratory infection that affects the lungs. It is caused by viruses, bacteria or fungi (germs). The viruses and bacteria that are commonly found in a child’s nose or throat can infect the lungs if they are inhaled. They may also spread via air-borne drops from a cough or sneeze.

Studies reveal that children whose immune systems are compromised are at higher risk of developing pneumonia. A child’s immune system may be weakened by malnutrition or under nourishment, especially in infants who are not exclusively breastfed, said Dr. Ashraf.

He added that HIV infections and measles also increase child’s risk of contracting pneumonia. Environmental factors such as indoor air pollution caused by cooking fires and heating with biomass fuels (such as wood or dung), living in crowded homes and parental smoking also increase a child’s susceptibility to pneumonia, he said.

He believes that ignoring early signs of pneumonia can be death sentence. “The symptoms of pneumonia include rapid or fast breathing, cough, fever, chills, loss of appetite, wheezing, and lower chest wall in drawing while severely ill infants may be unable to feed or drink and may also experience convulsions.”

To a query, Dr. Ashraf said that the good news is that pneumonia is preventable and treatable with host of proven interventions including exclusive breastfeeding to infants in their six months of life, ensuring an environment free of indoor air pollution and promoting frequent hand washing (protection); immunizing against leading causes (prevention); and ensuring access to medical care and antibiotics when cases do emerge (treatment).

He added that limiting exposure to smoke from cigarettes or indoor cook stoves and fires can help limit the risk of pneumonia. Research has shown that hand washing with soap and water can reduce the number of pneumonia-related infections in children under the age of five by more than 50 per cent, he said.

He added that immunizing against Hib (Haemophilus influenzae type B vaccine), pneumococcus, measles and whooping cough is the most effective way to prevent pneumonia. “The government of Pakistan has recently included pneumococcal vaccine in Expanded Program on Immunization and all parents having infants below six weeks of age can now get their children immunized against pneumonia free of cost.”

Dr. Ashraf said that pneumonia can be treated with antibiotics but only 30 per cent of the children receive antibiotics when needed. “Pneumonia-related child deaths can be reduced by 70 per cent by managing cases of pneumonia in children with antibiotics at the community level.” He said that Lady Health Workers can be trained to assess signs of pneumonia, determine appropriate treatment and advice parents, administer antibiotics and provide home care. The LHWs can also refer sick children to a healthcare facility if complications arise.

He added that children suffering from pneumonia can be treated promptly and effectively with antibiotics, however, overuse of antibiotics should be avoided in order to curb microbial resistance and children with upper respiratory tract infections (mainly coughs and colds) should not be prescribed unnecessary antibiotics. Similarly indiscriminate use of cough medicines should also be reduced.

Prevention and proper treatment of pneumonia could avert one million deaths in children every year while with proper treatment alone, over 600,000 deaths could be avoided, concluded Dr. Ashraf.

The News.com

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Friday, November 09, 2012

 

Viruses evolve to prevent bacterial hosts from committing suicide

Viruses evolve to prevent bacterial hosts from committing suicide

Nov 9, 2012

University of Cambridge researchers have discovered an extraordinary way that bacterial parasites prevent their hosts from killing themselves to protect the wider colony.

Researchers funded by BBSRC discovered that a strain of the potato soft rot and blackleg bacterium Pectobacterium atrosepticum (AKA Erwinia) had evolved to commit suicide in the presence of certain viral parasites, known as bacteriophages, to limit the spread of viral infection in the wider bacterial population.

Some mutant bacteriophages have evolved to stop their hosts from committing suicide.
Image: iStockphoto, Thinkstock 2012


The bacterial cells in a population that commit "suicide" by dying prematurely can be viewed as acting "altruistically", giving up their lives to prevent viral replication in siblings in the rest of the culture, in a process called abortive infection.

The paper, Viral Evasion of a Bacterial Suicide System by RNA-Based Molecular Mimicry Enables Infectious Altruism, published in PLoS Genetics on October 18 2012, also identified how the evolutionary arms race had produced low numbers of bacteriophage mutants that could suppress bacterial suicide in infected cells. These rare mutants (from a new transducing bacteriophage of the Myoviridae family) had evolved to produce an RNA antitoxin similar to that normally manufactured by the bacteria to suppress the lethality of the endogenous toxin, thus evading the suicide defence mechanism. By producing the mimic antitoxin, the virus could continue replicating without becoming a victim of the host's defensive system.

The mutant bacteriophage was also able to transfer DNA encoding the defense system to a new bacterial host. In doing so it may have indirectly created populations of host cells inside which it could successfully replicate while potentially providing the new host with better protection from competing viral predators.

Professor George Salmond, deputy head at Cambridge University's Department of Biochemistry, said: "This work highlights the incredibly dynamic world of adaptive co-evolution in bacteria and their viruses. The emergence of an RNA-based molecular mimicry in the virus to suppress bacterial suicide is an exciting observation.

"Furthermore, multiple alternative and novel routes, through which different bacteriophages may evolve to evade abortive infection, remain to be discovered. Because the bacteriophage investigated can pick up DNA from one bacterium and transfer it to a new host, this meant that escape mutants might be able to transfer the abortive infection system to other hosts - and that was confirmed. In effect, this could be viewed as an example of 'infectious altruism' - with a virus acting as a vector to transmit an anti-viral defense system between bacteria.
"Hypotheses about the molecular evolution of the "altruistic" trait, and possible adaptive impacts and fitness consequences (for both virus and bacterial host) can now be formally tested."

Healthcanal



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Fighting bacteria with mucus

Fighting bacteria with mucus
Nov 9 2012

Slimy layers of bacterial growth, known as biofilms, pose a significant hazard in industrial and medical settings. Once established, biofilms are very difficult to remove, and a great deal of research has gone into figuring out how to prevent and eradicate them.
Results from a recent Massachusetts Institute of Technology (MIT) study suggest a possible new source of protection against biofilm formation: polymers found in mucus. The MIT biological engineers found that these polymers, known as mucins, can trap bacteria and prevent them from clumping together on a surface, rendering them harmless.
"Mucus is a material that has developed over millions of years of evolution to manage our interactions with the microbial world. I'm sure we can find inspiration from it for new strategies to help prevent infections and bacterial colonization," says Katharina Ribbeck, the Eugene Bell Career Development Assistant Professor of Biological Engineering and senior author of the paper, which appears online in Current Biology.
Mucin coatings may help prevent biofilm formation on medical devices and could also find applications in personal hygiene: Incorporating them into products such as toothpaste or mouthwash may supplement the body's own defenses, especially in people whose natural mucus has been depleted, Ribbeck says.
Lead authors of the Current Biology paper are former MIT postdoctoral researcher Marina Caldara and Ronn Friedlander, a graduate student in the Harvard-MIT Division of Health Sciences and Technology. Other authors are Nicole Kavanaugh, an MIT graduate student in biology; Joanna Aizenberg, a professor of materials science at Harvard University; and Kevin Foster, a professor of evolutionary biology at the University of Oxford.
How to stop bacteria from teaming up
Mucus normally lines most of the wet surfaces of the body, including the respiratory and digestive tracts. "The textbook view of mucus is that it forms a barrier to infection, but it's not at all clear how it does so," Ribbeck says.
To investigate that question, Ribbeck and her colleagues observed the behavior ofPseudomonas aeruginosa bacteria in a growth medium that contained soluble purified mucins—long proteins with many sugar molecules attached.
For bacteria to effectively penetrate the mucus layer and infect the tissues below, they need to form clusters that can adhere to the tissue surface. Clumps of bacteria are much more difficult for the immune system to clear, because immune cells are specialized to attack individual bacterial cells.
"In general, you want to have bacteria around, you just don't want them to team up," Ribbeck says. "You want to them to be mixed with many other bacteria that are good for you. You don't want a single species to take over, because then they may overgrow the system."
In the new study, the researchers found that mucins block bacterial cluster formation by preventing them from adhering, which is necessary for them to clump together. When bacteria stay motile, they end up suspended in a gooey mix and can do less harm.
"The mucins have the ability to suppress virulence by keeping the cells separate. It's like keeping your kids in separate rooms, so they will stay out of trouble," Ribbeck says.
However, bacteria are sometimes able to break through this defense system and cause infections. This can be accelerated by reductions in mucus due to aging, dehydration, or chemotherapy, Ribbeck says. Or it may be that the mucus does not get replaced often enough, as happens in the mucus-clogged lungs of cystic fibrosis patients.
The finding contradicts a long-held belief that mucus is merely a sticky substance that traps more or less everything, says Gunnar C. Hansson, a professor of medical biochemistry at the University of Gothenburg in Sweden. It also "opens a new window for studies of mucins and their properties, which will help us to develop new medical therapies and biotechnological applications," says Hansson, who was not part of the research team.
'Managing microbial behavior'
One advantage of using mucins as antimicrobial coatings is that the substance disarms pathogenic bacteria without killing them. This makes it less likely that bacteria could evolve resistance to mucins, as they do to antibiotic drugs. It would also spare the beneficial bacteria that live on mucus membranes.
"This is a nice mechanism where you just suppress the virulence traits without killing the bacteria," Ribbeck says. "It's nature's way of managing microbial behavioral in a way that could be useful to take advantage of."
Her laboratory is now investigating exactly how mucins prevent bacteria from losing their motility, and also how they block infection by nonmotile bacteria. Mucins seem to have wide-ranging antimicrobial properties: Ribbeck has previously shown that they can trap viruses and keep them from infecting cells, and she is now studying mucin interactions with other pathogenic organisms, such as yeasts.
Source: Massachusetts Institute of Technology

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