Antibiotic Resistance Spreads Rapidly Between Bacteria

ScienceDaily (Apr. 11, 2011) — The part of bacterial DNA that often carries antibiotic resistance is a master at moving between different types of bacteria and adapting to widely differing bacterial species, shows a study made by a research team at the University of Gothenburg in cooperation with Chalmers University of Technology.

Antibiotic resistance-carrying plasmids from different bacteria can meet and exchange genetic material. The result is plasmids consisting of genes that have each been adapted to different bacterial species. This facilitates further adaptation and mobility, and consequently also the spread of antibiotic resistance between different bacterial species.

The results are published in an article in the scientific journal Nature Communications.

More and more bacteria are becoming resistant to our common antibiotics, and to make matters worse, more and more are becoming resistant to all known antibiotics. The problem is known as multi-resistance, and is generally described as one of the most significant future threats to public health Antibiotic resistance can arise in bacteria in our environment and in our bodies. Antibiotic resistance can then be transferred to the bacteria that cause human diseases, even if the bacteria are not related to each other.

A large proportion of gene transfer between bacteria takes place with the aid of what are known as conjugative plasmids, a part of the bacterial DNA. A plasmid can only exist and multiply inside a cell, where it uses the cell's machinery, but can then be transferred to another cell and in that way spread between bacteria.

The research team has studied a group of the known carriers of antibiotic resistance genes: IncP-1 plasmids. Using advanced DNA analysis, the researchers have succeeded in mapping the origin of different IncP-1 plasmids and their mobility between different bacterial species. "Our results show that plasmids from the IncP-1 group have existed in, and adapted to, widely differing bacteria. They have also recombined, which means that a single plasmid can be regarded as a composite jigsaw puzzle of genes, each of which has adapted to different bacterial species," says Peter Norberg, a researcher in the Institute of Biomedicine at the University of Gothenburg. This indicates very good adaptability and suggests that these plasmids can move relatively freely between, and thrive in, widely differing bacterial species.

"IncP-1 plasmids are very potent 'vehicles' for transporting antibiotic resistance genes between bacterial species. Therefore, it does not matter much in what environment, in what part of the world, or in what bacterial species antibiotic resistance arises. Resistance genes could relatively easily be transported from the original environment to bacteria that infect humans, through IncP-1 plasmids, or other plasmids with similar properties, as 'vehicles'," says Professor Malte Hermansson of the Department of Cell and Molecular Biology at the University of Gothenburg.

It has been known for some time that plasmids are important in the spread of antibiotic resistance. The research team's findings show that IncP-1 plasmids can move, and have moved, between widely differing bacterial species and in addition have interacted directly with one another, which can increase the potential for gene spreading.

New Antibiotics Against Resistant Bacterial Infections Discovered

ScienceDaily (Apr. 8, 2011) — This year's World Health Day focuses on the growing threat of potentially deadly infections developing resistance to antimicrobial drugs -- especially to antibiotics. On this occasion, the European Commission is presenting the promising results of two EU-funded international research projects which provide new hopes to help and treat people. In the European Union alone, it is estimated that drug resistant infections cause more than 25,000 deaths and €1.5 billion in extra healthcare costs every year.

A new substance to tackle drug resistant tuberculosis

The project NM4TB, which gathers 18 research teams from 13 countries, discovered a novel class of substances, called benzothiazinones (BTZ), that could be used in the treatment of tuberculosis and drug resistant tuberculosis. These substances act by preventing the bacteria that cause tuberculosis from constructing their cell wall. This discovery represents an important breakthrough in the battle against tuberculosis as the most advanced compound of this new class, BTZ043, is also effective against extensively drug resistant tuberculosis (XDR-TB).

Exploiting genetic resources to find new antibiotics

18 research teams from 9 European countries and the Republic of Korea joined forces in the project ActinoGEN to discover and develop new antibiotics by exploiting the genetic resources of a group of bacteria called actinomycetes. Previous studies on the genomes of actinomycetes suggested that these bacteria had the potential to produce many new antibiotics. The researchers identified one entirely novel lead antibiotic by exploring the bacterial species Streptomyces ambofaciens, and engineered additional antibiotics by combinatorial biosynthesis. The project has generated 8 patents.

Background

A wide array of microorganisms, including bacteria, viruses, protozoa and fungi, are becoming resistant to drugs that are used to treat infections. This resistance, which is called antimicrobial resistance (AMR), is a major obstacle to the treatment of infectious diseases worldwide. Faced with the extent of AMR, and the dwindling number of effective antimicrobial drugs, the World Health Organization (WHO) has stated that it considers AMR to be one of the greatest threats to human health.

Tackling AMR requires investing in research and innovation. The EU has prioritised research in this field, supporting numerous research projects with a total amount of approximately €300 million since 1999. Priorities include developing novel medicines and therapies, defining the optimal use of existing antimicrobial drugs, developing diagnostic tools, monitoring the spread of resistance and basic research on pathogenic organisms. EU-funded projects have helped to better understand resistance mechanisms and to identify novel antimicrobial compounds that may lead to future drugs.

Pesquisadores estudam capacidade evolutiva de bactérias

Desde a época de Darwin, os biólogos reconhecem a evolução da vida. Porém, nos últimos 25 anos, alguns pesquisadores argumentam que certos organismos são melhores em evoluir do que outros pelas diferenças de seus genomas.

As espécies com menos probabilidade de evoluir, em contraste, são rígidas demais para tirar vantagem das novas mutações ou para encontrar novas soluções para a sobrevivência.

Muitos biólogos concordam que a capacidade de evoluir faz sentido na teoria. No entanto, encontrar evidências no mundo natural tem se mostrado difícil.

Parte do problema é que a seleção natural pode levar um longo tempo para agir numa espécie. Também é difícil para os pesquisadores identificarem as mutações por trás da evolução.

Mas na edição mais recente da "Science", uma equipe de pesquisadores relata um exemplo detalhado sobre a capacidade evolutiva em ação, que ocorreu bem diante de seus olhos num laboratório.

"Acho um trabalho brilhante", diz um dos pesquisadores líderes sobre a capacidade evolutiva, Massimo Pigliucci, professor do Lehman College no Bronx, Nova York.

PESQUISA DESDE 1988

O novo estudo surgiu a partir do experimento contínuo mais duradouro sobre a evolução, iniciado em 1988 quando Richard E. Lenski, hoje na Universidade do Estado de Michigan, colocou em 12 frascos cópias idênticas de Escherichia coli. Ele e seus colegas cultivaram a bactéria com uma dieta escassa de glicose desde então.

Ao longo das 52 mil gerações, a bactéria se adaptou ao ambiente peculiar. A cada 500 gerações, Lenski e seus colegas congelam algumas das bactérias, que podem ser aquecidas para serem comparadas a seus descendentes evoluídos.

Lenski e seus colegas selecionaram uma das 12 linhagens para um estudo mais próximo. "Queríamos rastrear a ordem nas quais as mutações apareciam e tirar um sentido disso", conta.

Os cientistas observaram que, após 500 gerações, dois tipos de E. coli eram dominantes no frasco, cada uma com um conjunto distinto de mutações. No entanto, após mil gerações, apenas um tipo permaneceu. Lenski e seus colegas o batizaram de "ganhadores".

Eles quiseram demonstrar o curso dessa vitória sobre os perdedores e aqueceram ambos os tipos da 500ª geração, e fizeram com que competissem entre si. Os cientistas esperavam que o resultasse fosse uma conclusão inevitável: os vencedores já estariam mostrando sua superioridade. Ainda assim, o experimento foi feito em nome da exatidão.

"Queríamos colocar os pingos nos is", explica Lenski.

NÃO É O QUE PARECE

Para surpresa dos pesquisadores, eles estavam errados. Na 500ª geração, os supostos perdedores eram muito superiores, crescendo 6,5% mais rápido do que os que seriam vencedores. Nesse ritmo, eles levariam os supostos vencedores à extinção em 350 gerações.

Os cientistas viram duas possíveis explicações para essa reviravolta. Uma é que os vencedores eram mais propensos a evoluir e tinham mais potencial para aumentar seu índice de crescimento, permitindo que chegassem e ganhassem a corrida evolucionária.

A outra possibilidade é a de que os vencedores eram apenas seres de sorte: em algum momento após a 500ª geração, desenvolveram mutações benéficas que lhes trouxeram vantagem.

"Uma pessoa que não sabe jogar cartas pode ser um jogador melhor de vez em quando só por ter pego uma sequência real", ilustra Lenski.

Ele e seus colegas organizaram um novo experimento para analisar as duas possibilidades, descongeladno alguns dos vencedores da 500ª geração que foram usados para dar origem a 20 novas linhagens de bactérias. Da mesma forma, iniciaram 20 outras novas linhagens com os supostos perdedores.

A partir daí, os cientistas permitiram que todas as bactérias descongeladas se reproduzissem por 883 gerações.

Os supostos vencedores ainda derrotaram consistentemente os supostos perdedores, como descobriram os pesquisadores. Em média, eles acabaram crescendo 2,1% mais rápido que seus rivais. Em outras palavras, seu sucesso não foi resultado de boa sorte. Eles eram mais bem preparados para aproveitar ao máximo as mutações benéficas.

Os experimentos permitiram que os cientistas reconstruíssem a corrida evolucionária. Os supostos perdedores inicialmente assumiram a liderança com mutações que lhes deram um aumento de curto prazo em seu ritmo de crescimento.

Porém, essas mutações levaram a uma derrota no longo prazo porque, quando as mutações benéficas adicionais apareceram, os perdedores tiveram apenas um pequeno aumento em seu ritmo de crescimento. Os ganhadores, por outro lado, apresentaram maior benefício com mutações posteriores, permitindo que abrissem vantagem e dominassem o frasco.

Pigliucci afirma que a capacidade evolutiva poderia explicar vários importantes padrões na natureza, como por que alguns animais possuem muitas formas diferentes, enquanto seus parentes próximos não mudaram muita coisa em centenas de milhões de anos.

Isso significaria que a capacidade de evoluir precisaria estar presente na luta pela sobrevivência geração após geração. E o experimento de Lenski documenta que isso pode, de fato, fazer a diferença para organismos reais.

'Knowing It in Your Gut': Cross-Talk Between Human Gut Bacteria and Brain

ScienceDaily (Mar. 24, 2011) — A lot of chatter goes on inside each one of us and not all of it happens between our ears. Researchers at McMaster University discovered that the "cross-talk" between bacteria in our gut and our brain plays an important role in the development of psychiatric illness, intestinal diseases and probably other health problems as well including obesity.

Gut bacteria influence anxiety-like behavior through alterations in the way the brain is wired, new research suggests.

"The wave of the future is full of opportunity as we think about how microbiota or bacteria influence the brain and how the bi-directional communication of the body and the brain influence metabolic disorders, such as obesity and diabetes," says Jane Foster, associate professor in the Department of Psychiatry and Behavioural Neurosciences of the Michael G. DeGroote School of Medicine.

Using germ-free mice, Foster's research shows gut bacteria influences how the brain is wired for learning and memory. The research paper has been published in the March issue of the science journalNeurogastroenterology and Motility.

The study's results show that genes linked to learning and memory are altered in germ-free mice and, in particular, they are altered in one of the key brain regions for learning and memory -- the hippocampus.

"The take-home message is that gut bacteria influences anxiety-like behavior through alterations in the way the brain is wired," said Foster.

Foster's laboratory is located in the Brain-Body Institute, a joint research initiative of McMaster University and St. Joseph's Healthcare in Hamilton. The institute was created to advance understanding of the relationship between the brain, nervous system and bodily disorders.

"We have a hypothesis in my lab that the state of your immune system and your gut bacteria -- which are in constant communication -- influences your personality," Foster said.

She said psychiatrists, in particular, are interested in her research because of the problems of side effects with current drug therapy.

"The idea behind this research is to see if it's possible to develop new therapies which could target the body, free of complications related to getting into the brain," Foster said. "We need novel targets that take a different approach than what is currently on the market for psychiatric illness. Those targets could be the immune system, your gut function…we could even use the body to screen patients to say what drugs might work better in their brain."

Scientists Grow Personalized Collections of Intestinal Microbes

ScienceDaily (Mar. 23, 2011) — Each of us carries a unique collection of trillions of friendly microbes in our intestines that helps break down food our bodies otherwise couldn't digest

Scientists at Washington University School of Medicine in St. Louis show they can grow and manipulate personalized collections of human intestinal microbes in the laboratory and pluck out particular microbes of interest. The research sets the stage for identifying new probiotics and evaluating in preclinical trials whether microbe transplants can restore the natural balance of intestinal bacteria in "sick" microbial communities. 

This relationship between humans and their microbes is generally a healthy one, but changes to the mix of microbes in the digestive tract are suspected to play a role in obesity, malnutrition, Crohn's disease and other ailments.

Now, scientists at Washington University School of Medicine in St. Louis show they can grow and manipulate personalized collections of human intestinal microbes in the laboratory and pluck out particular microbes of interest.

The research sets the stage for identifying new probiotics and evaluating in preclinical trials whether microbe transplants can restore the natural balance of intestinal bacteria in "sick" microbial communities.

The research, by Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Center for Genome Sciences & Systems Biology, and his team is reported online March 21 in the early online edition of the Proceedings of the National Academy of Sciences.

"This research helps set up a discovery pipeline in which we can deliberately manipulate collections of human intestinal microbes from people of different ages and cultures who are either healthy or sick," says Gordon, whose research first established a possible link between obesity and other facets of nutritional status and the mix of microbes that inhabit the intestine. "This gives us the opportunity to identify new groups of microbes that may be extremely beneficial in various therapeutic settings."

Researchers have grown bacterial microbes in the laboratory before, but until recently there's been no reliable way to know whether communities captured in a Petri dish mirror the extensive bacterial collections that exist in particular habitats of the body, such as the intestine.

"There are so many types of bacteria that live in different parts of our bodies, as well as substantial differences in these collections from person to person, that most scientists have thought we're probably missing a lot of the richness of microbial communities when we try to grow them in the laboratory," Gordon says. "But we found that the ability to successfully grow collections of gut microbes is much greater than had been expected."

For the study, the researchers obtained stool samples from two unrelated people. A portion of each sample was grown in the laboratory under strict "anaerobic" conditions because gut microbes live in an environment that lacks oxygen.

Then, they used the latest DNA sequencing technology to sequence a gene found in all microbes. This gene, 16S rDNA, functions as a barcode of life to determine "who" is there and can be used to inventory the various species present in a microbial community.

In all, they discovered that most of the different groups of intestinal bacteria found in an individual also were present in their corresponding bacterial collections that were grown, or cultured, in the laboratory.

"We were able to capture a remarkable proportion of the diversity of each person's intestinal bacteria in the samples we grew in the laboratory," says first author Andrew Goodman, PhD, a former postdoctoral student in Gordon's lab who is now on the faculty at Yale University.

The researchers then transplanted collections of microbial communities from the cultured and uncultured samples into the intestinal tracts of formerly germ-free mice. The mice, in essence, acquired a collection of gut microbes that mimicked the community in the original human donor.

By analyzing these "humanized" mice, the researchers demonstrated that both cultured and uncultured gut microbial communities from the same person behaved in the same manner when the mice were switched from their typical diet -- a low-fat, plant-based mouse chow -- to a standard western diet that is high in fat and sugar. Some species became more dominant and others less so, but the changes were virtually identical, regardless of whether the original sample was cultured or not.

The researchers also demonstrated they could split apart an entire community of cultured intestinal microbes and create a "personalized" library of bacterial species.

Microbes that react strongly to changes in diet or exposure to antibiotics, for example, can be retrieved from these libraries and their genomes can be sequenced to help understand why they respond as they do. Then, these microbes can be reunited with other members of a microbial community in germ-free mice to create more simplified models of human gut communities.

Gordon envisions that this approach makes it possible to obtain personalized microbial communities from people around the world who consume different diets and from individuals who are obese or malnourished or who have Crohn's or other diseases.

"This gives us the ability to test the contributions of specific microbes or groups of microbes and their influence on a person's health," Gordon explains. "One central question we hope to answer is how much of a person's overall nutritional status can be ascribed to their gut microbes and whether nutritional status can be improved by therapeutic interventions directed to gut microbial communities."

The research is funded by the National Institutes of Health and the Crohn's and Colitis Foundation of America.

Cientistas encontram bactérias vivas enterradas em sal há 34 mil anos

Segundo estudos, a base da sobrevivência desses micro seres é um organismo unicelular, chamado alga Dunaliella. Essa alga produz carvão que servem de sustento às bactérias, que vivem durante períodos imprevisíveis

WASHINGTON - Um complexo ecossistema de bactérias devoradoras de sal sobrevive há 34 mil anos enterrado em fluidos no interior de minerais de Death Valley e Saline Valley, no estado americano da Califórnia, tal como revela um estudo publicado nesta quinta-feira, 13.

A halita, como se denomina o mineral formado por cristais de cloreto de sódio, foi o lar dessas bactérias, procariotas e eucariotas, durante dezenas de milhares de anos, segundo o estudo, publicado na edição de janeiro da revista da Sociedade Geológica Americana, GSA Today.

Segundo o autor do texto, o cientista Brian A. Schubert, do Departamento de Estudos Geológicos da Universidade do Estado de Nova York, as bactérias estão vivas, mas a vida delas é limitada à sobrevivência, pois não usam energia para nadar e nem para se reproduzirem.

A base de sua sobrevivência é um organismo unicelular, chamado alga Dunaliella, presente em muitos sistemas salinos. Esse organismo produz carvão e outros metabolitos que servem de sustento às bactérias.

Assim, os organismos podem sobreviver, durante períodos imprevisíveis, flutuando em fluidos no interior dos minerais.

"A parte mais emocionante (da pesquisa) foi quando pudemos identificar as células de Dunaliella nos cristais, porque eram indícios de que poderia haver uma fonte de alimento", explicou Schubert ao site Our Amazing World.

O rápido crescimento dos cristais de sal, que envolvem todos os fluidos em pequenas borbulhas protegidas em seu interior, é outra das razões da surpreendente longevidade das bactérias, segundo o estudo.

A pesquisa de Schubert e sua equipe não é a primeira descoberta de organismos tão antigos, pois já foram publicados inclusive estudos que falam de bactérias vivas de mais de 250 milhões de anos, mas é a primeira em que os cientistas comprovaram suas conclusões repetindo os testes.

Segundo Schubert, a prova de que seu estudo não é manipulado é que conseguiu fazer com que os organismos voltassem a crescer uma segunda vez, e quando enviou os cristais a outro laboratório, obteve os mesmos resultados.

Os cientistas ainda não determinaram, no entanto, como as bactérias conseguiram sobreviver durante tantos milhares de anos com o sustento tão mínimo que a alga lhes proporcionava.

A equipe pretende agora aprofundar essa pesquisa e contrastá-la com outros estudos que exploram a vida microbiana na terra e no sistema solar, onde existem materiais de inclusive bilhões de anos de idade que são potencialmente capazes de abrigar microorganismos.

Por enquanto, Schubert e seus colegas conseguiram algo pouco comum: que bactérias se reproduzam pela primeira vez em milhares de anos.

Cinco dos 900 cristais de sal analisados pela equipe produziram novas bactérias vivas, indicou Schubert. Segundo ele, os micróbios demoraram cerca de dois meses e meio para "despertar" de seu estado de letargia antes de começar a se reproduzir.