Tips from the journals of the American Society for Microbiology

Public release date: 21-May-2012
[ | E-mail | Share ]

Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology

May 2012

Genes Culled From Desert Soils Suggest Potential Medical Resource

Despite their ecologic similarity, soils from three geographically distinct areas of the American southwest harbor vastly different collections of small, biosynthetic genes, a finding that suggests the existence of a far greater diversity of potentially useful products than was previously supposed. The research is published in the May issue of Applied and Environmental Microbiology.

Natural compounds have been the sources of the majority of new drugs approved by the US Food and Drug Administration, and bacteria have been the biggest single source of these therapeutically relevant compounds. Most bacterially-derived antibiotic and anticancer agents were discovered by culturing bacteria from environmental samples, and then examining the metabolites they produce in laboratory fermentation studies. But the vast majority of bacterial species cannot be cultured, which suggested that the world might be awash in potentially useful, but unknown bacterial metabolites.

In this study, Sean Brady of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, and colleagues extracted DNA from soils from the Sonoran Desert of Arizona, the Anza Borrego section of the Sonoran Desert of California, and the Great Basin Desert of Utah. They used this DNA to construct very large metagenomic DNA libraries, and screened these libraries for three of the most common classes of small molecule biosynthesis systems, type I modular polyketides, type II iterative polyketides, and non-ribosomal peptides, says Brady.

The investigators used PCR to amplify collections of gene fragments from each of the three libraries and compared these to assess the similarities and differences between the collections of genes cloned from each environment, says Brady.

"Our work suggests that the genomes of environmental bacteria could encode many additional drug-like molecules, including compounds that might serve, among other things, as new antibiotics and anticancer agents," says Brady. "This is a small preliminary study that warrants additional investigations of more environments and more extensive sequence analysis, but it suggests that environmental bacteria have the potential to encode a large additional treasure trove of new medicines."

(B.V.B. Reddy, D. Kallifidas, J.H. Kim, Z. Charlop-powers, Z. Feng, and S.F. Brady, 2012. Natural product biosynthetic gene diversity in geographically distinct soil microbiomes. Appl. Environ. Microbiol. 78:3744-3752.)

Download a copy of the journal article at: http://bit.ly/asm052112a

---

Garlic Constituent Blocks Biofilm Formation, Could Benefit CF Patients and Others

E Pluribus Unum, the motto of the United States, could just as well apply to biofilm-forming bacteria. Bacterial biofilms are far more resistant than individual bacteria to the armories of antibiotics we have devised to combat them. Now Tim Holm Jakobsen and Michael Givskov of the University of Copenhagen, and their many collaborators have pinpointed a constituent of garlic that attacks a key step in the development of biofilms, in an effort they hope may offer help in particular for patients with cystic fibrosis. The research is published in the May 2012 issue of Antimicrobial Agents and Chemotherapy.

In earlier work, Givskov and his colleagues showed that "crude extracts of garlic inhibit the expression of a large number of genes that are controlled by bacterial quorum sensing [communication among bacterial cells involved in biofilm development], and that extracts promote a rapid clearing of pulmonary Pseudomonas aeruginosa infection in mice," he says. "These findings encouraged us to identify and assess the efficacy of the pure active compound."

That compound turned out to be ajoene, the major constituent of a multitude of sulfur-containing compounds produced when garlic is crushed, says Jakobsen. The team then showed in P. aeruginosa that ajoene inhibits expression of 11 genes that are controlled by quorum sensing. "These key genes are regarded as crucial for the ability of P. aeruginosa to cause disease," he says.

"We also found ajoene to reduce the production of rhamnolipid, a compound that shields the biofilm bacteria from the white blood cells that otherwise would destroy bacteria, and that by combining ajoene with the antibiotic tobramycin, it was possible to kill over 90 percent of bacteria living in a biofilm," says Jakobsen.

"Our study is part of a series of comprehensive investigations of natural compounds targeting bacterial quorum sensing systems, and it further strengthens previous proof of concept research we conducted on the potential of compounds which block communication among pathogen cells in contrast to simply killing bacteria, as conventional antibiotics do," says Jakobsen. Such alternative approaches "may postpone or minimize development of antibiotic resistance," he adds.

Jakobsen says the garlic project grew out of a major donation from the German Cystic Fibrosis Association. "In CF patients, P. aeruginosa infection leads to bronchieciasis, pulmonary fibrosis, respiratory failure, and death," he says. "Despite intensive antibiotic traatment, CF patients have a life expectancy of about 40 years, and the main cause of death in CF patients remains complications associated with [this infection]." Jakobsen's team and the German CF Association have patented the action of ajoene against biofilms, and are seeking a pharmacutical partner to develop antimicrobial drugs based on ajoene.

Jakobsen notes that garlic has been used medicinally "for thousands of years." Garlic not only has antibacterial properties; it has anti-viral, anti-fungal, and anti-protozoal properties as well, and it has beneficial effects on the cardiovascular and immune systems, as well, he says.

(T.H. Jakobsen, M. van Gennip, M. Givskov, et al. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antim. Agents Chemother. 56:2314-2325.)

Download a copy of the journal article at: http://bit.ly/asm052112b

---

Experimental Vaccine Elicits Robust Response Against Both HIV and Tuberculosis

Clinician researchers in China have developed a vaccine that acts simultaneously against HIV-1 and M. tuberculosis (Mtb). An estimated 14 million people worldwide are coinfected with the two pathogens. The research is published in the May 2012 issue of Clinical and Vaccine Immunology.

The vaccine is composed of antigens from both pathogens. The team, led by Sidong Xiong of Fudan University, Shanghai, incorporated four Mtb epitopes (the part of an antigen that is recognized by the immune system) into a backbone composed of HIV-1 p24 protein, a protein that is known to produce protective immunity against HIV-1. The logic of this construction: many epitopes are short peptides, with poor immunogenicity unless they are introduced into a carrier proteinwhich in this case was the p24 protein.

The vaccine induced cellular immune responses to both pathogens, in which immune system cells including macrophages search out and destroy pathogens; and humoral immune response against HIV-1, in which the immune system produces antibodies against the pathogen. The vaccine was tested in a mouse model.

Tuberculosis is one of the leading causes of death worldwide; third, after hepatitis C and then HIV/AIDS among infectious diseases, according to the World Health Organization (WHO). An estimated 2 billion28 percent of the world's populationare infected with M. tuberculosis, but most of these infections are latent. However, HIV infection is the strongest risk factor for the progression of latent tuberculosis infection to active TB. And TB is the direct cause of death in about one quarter of all deaths among people with HIV/AIDS, according to the WHO.

(X. Li, W. Xu, and S. Xiong, 2012. A novel tuberculosis DNA vaccine in an HIV-1 p24 protein backbone confers protection against Mycobacterium tuberculosis and simultaneously elicits robust humoral and cellular responses to HIV-1. Clin. Vac. Immunol. 19:723-730.)

Download a copy of the journal article at: http://bit.ly/asm052112c

---

Antibiotics Boost Risk of Infection with Antifungal-Resistant Candida

Previous exposure to certain antibiotics could boost the risk of infection with drug-resistant strains of a severe fungal infection. Researchers report their findings in the May 2012 issue of the journal Antimicrobial Agents and Chemotherapy.

Candida species are frequent causes of hospital acquired infection. Patients at greatest risk are those with "prolonged hospitalization, abdominal surgery, antibiotic treatment, neutropenia, and central venous catheterization," the researchers write. Candidemia leads to high rates of "attributable" mortality, longer hospitalizations, and "excessive costs."

Ronen Ben-Ami of Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, and his colleagues identified 444 patients who had Candida growing in their blood; 8.5 percent of whom were infected with Candida strains that were resistant to fluconazole, an important antifungal used to treat this infection. For all 444 patients, the researchers obtained detailed histories of antibiotic exposure during the month prior to onset of candidemia. They found that previous exposure to four antibiotic drugs or drug classes increased the risk of infection with fluconazole-resistant Candida nearly three-fold.

"A striking feature of the current cohort of patients with candidemia is the almost universal exposure to antibacterial drugs in the preceding month," the researchers write. "Moreover, the majority of patients received multiple classes of antibacterials, either concomitantly or sequentially."

"Our findings underscore the importance of limiting the use of antibiotics to those situations where these drugs are strictly indicated," says Ben-Ami. He further recommends that clinicians treating patients with candidemia should take the patient's recent antibiotic exposure history into account when selecting the antifungal treatment. "Clinicians should be aware that patients who have recently been treated with certain antibiotics are at increased risk of infection with drug-resistant candida, which in turn could lead to treatment failure," he says. "Previous research has shown that around one third of antibiotic prescriptions are unnecessary."

(R. Ben-Ami, K. Olshtain-Pops, M. Giladi, et al. for the Israeli Candidemia Study Group, 2012. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bnloodstream infection. Antim. Agents Chemother. 56:2518-2523.)

Download a copy of the journal article at: http://bit.ly/asm052112d

###

---

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 21-May-2012
[ | E-mail | Share ]

Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology

May 2012

Genes Culled From Desert Soils Suggest Potential Medical Resource

Despite their ecologic similarity, soils from three geographically distinct areas of the American southwest harbor vastly different collections of small, biosynthetic genes, a finding that suggests the existence of a far greater diversity of potentially useful products than was previously supposed. The research is published in the May issue of Applied and Environmental Microbiology.

Natural compounds have been the sources of the majority of new drugs approved by the US Food and Drug Administration, and bacteria have been the biggest single source of these therapeutically relevant compounds. Most bacterially-derived antibiotic and anticancer agents were discovered by culturing bacteria from environmental samples, and then examining the metabolites they produce in laboratory fermentation studies. But the vast majority of bacterial species cannot be cultured, which suggested that the world might be awash in potentially useful, but unknown bacterial metabolites.

In this study, Sean Brady of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, and colleagues extracted DNA from soils from the Sonoran Desert of Arizona, the Anza Borrego section of the Sonoran Desert of California, and the Great Basin Desert of Utah. They used this DNA to construct very large metagenomic DNA libraries, and screened these libraries for three of the most common classes of small molecule biosynthesis systems, type I modular polyketides, type II iterative polyketides, and non-ribosomal peptides, says Brady.

The investigators used PCR to amplify collections of gene fragments from each of the three libraries and compared these to assess the similarities and differences between the collections of genes cloned from each environment, says Brady.

"Our work suggests that the genomes of environmental bacteria could encode many additional drug-like molecules, including compounds that might serve, among other things, as new antibiotics and anticancer agents," says Brady. "This is a small preliminary study that warrants additional investigations of more environments and more extensive sequence analysis, but it suggests that environmental bacteria have the potential to encode a large additional treasure trove of new medicines."

(B.V.B. Reddy, D. Kallifidas, J.H. Kim, Z. Charlop-powers, Z. Feng, and S.F. Brady, 2012. Natural product biosynthetic gene diversity in geographically distinct soil microbiomes. Appl. Environ. Microbiol. 78:3744-3752.)

Download a copy of the journal article at: http://bit.ly/asm052112a

---

Garlic Constituent Blocks Biofilm Formation, Could Benefit CF Patients and Others

E Pluribus Unum, the motto of the United States, could just as well apply to biofilm-forming bacteria. Bacterial biofilms are far more resistant than individual bacteria to the armories of antibiotics we have devised to combat them. Now Tim Holm Jakobsen and Michael Givskov of the University of Copenhagen, and their many collaborators have pinpointed a constituent of garlic that attacks a key step in the development of biofilms, in an effort they hope may offer help in particular for patients with cystic fibrosis. The research is published in the May 2012 issue of Antimicrobial Agents and Chemotherapy.

In earlier work, Givskov and his colleagues showed that "crude extracts of garlic inhibit the expression of a large number of genes that are controlled by bacterial quorum sensing [communication among bacterial cells involved in biofilm development], and that extracts promote a rapid clearing of pulmonary Pseudomonas aeruginosa infection in mice," he says. "These findings encouraged us to identify and assess the efficacy of the pure active compound."

That compound turned out to be ajoene, the major constituent of a multitude of sulfur-containing compounds produced when garlic is crushed, says Jakobsen. The team then showed in P. aeruginosa that ajoene inhibits expression of 11 genes that are controlled by quorum sensing. "These key genes are regarded as crucial for the ability of P. aeruginosa to cause disease," he says.

"We also found ajoene to reduce the production of rhamnolipid, a compound that shields the biofilm bacteria from the white blood cells that otherwise would destroy bacteria, and that by combining ajoene with the antibiotic tobramycin, it was possible to kill over 90 percent of bacteria living in a biofilm," says Jakobsen.

"Our study is part of a series of comprehensive investigations of natural compounds targeting bacterial quorum sensing systems, and it further strengthens previous proof of concept research we conducted on the potential of compounds which block communication among pathogen cells in contrast to simply killing bacteria, as conventional antibiotics do," says Jakobsen. Such alternative approaches "may postpone or minimize development of antibiotic resistance," he adds.

Jakobsen says the garlic project grew out of a major donation from the German Cystic Fibrosis Association. "In CF patients, P. aeruginosa infection leads to bronchieciasis, pulmonary fibrosis, respiratory failure, and death," he says. "Despite intensive antibiotic traatment, CF patients have a life expectancy of about 40 years, and the main cause of death in CF patients remains complications associated with [this infection]." Jakobsen's team and the German CF Association have patented the action of ajoene against biofilms, and are seeking a pharmacutical partner to develop antimicrobial drugs based on ajoene.

Jakobsen notes that garlic has been used medicinally "for thousands of years." Garlic not only has antibacterial properties; it has anti-viral, anti-fungal, and anti-protozoal properties as well, and it has beneficial effects on the cardiovascular and immune systems, as well, he says.

(T.H. Jakobsen, M. van Gennip, M. Givskov, et al. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antim. Agents Chemother. 56:2314-2325.)

Download a copy of the journal article at: http://bit.ly/asm052112b

---

Experimental Vaccine Elicits Robust Response Against Both HIV and Tuberculosis

Clinician researchers in China have developed a vaccine that acts simultaneously against HIV-1 and M. tuberculosis (Mtb). An estimated 14 million people worldwide are coinfected with the two pathogens. The research is published in the May 2012 issue of Clinical and Vaccine Immunology.

The vaccine is composed of antigens from both pathogens. The team, led by Sidong Xiong of Fudan University, Shanghai, incorporated four Mtb epitopes (the part of an antigen that is recognized by the immune system) into a backbone composed of HIV-1 p24 protein, a protein that is known to produce protective immunity against HIV-1. The logic of this construction: many epitopes are short peptides, with poor immunogenicity unless they are introduced into a carrier proteinwhich in this case was the p24 protein.

The vaccine induced cellular immune responses to both pathogens, in which immune system cells including macrophages search out and destroy pathogens; and humoral immune response against HIV-1, in which the immune system produces antibodies against the pathogen. The vaccine was tested in a mouse model.

Tuberculosis is one of the leading causes of death worldwide; third, after hepatitis C and then HIV/AIDS among infectious diseases, according to the World Health Organization (WHO). An estimated 2 billion28 percent of the world's populationare infected with M. tuberculosis, but most of these infections are latent. However, HIV infection is the strongest risk factor for the progression of latent tuberculosis infection to active TB. And TB is the direct cause of death in about one quarter of all deaths among people with HIV/AIDS, according to the WHO.

(X. Li, W. Xu, and S. Xiong, 2012. A novel tuberculosis DNA vaccine in an HIV-1 p24 protein backbone confers protection against Mycobacterium tuberculosis and simultaneously elicits robust humoral and cellular responses to HIV-1. Clin. Vac. Immunol. 19:723-730.)

Download a copy of the journal article at: http://bit.ly/asm052112c

---

Antibiotics Boost Risk of Infection with Antifungal-Resistant Candida

Previous exposure to certain antibiotics could boost the risk of infection with drug-resistant strains of a severe fungal infection. Researchers report their findings in the May 2012 issue of the journal Antimicrobial Agents and Chemotherapy.

Candida species are frequent causes of hospital acquired infection. Patients at greatest risk are those with "prolonged hospitalization, abdominal surgery, antibiotic treatment, neutropenia, and central venous catheterization," the researchers write. Candidemia leads to high rates of "attributable" mortality, longer hospitalizations, and "excessive costs."

Ronen Ben-Ami of Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, and his colleagues identified 444 patients who had Candida growing in their blood; 8.5 percent of whom were infected with Candida strains that were resistant to fluconazole, an important antifungal used to treat this infection. For all 444 patients, the researchers obtained detailed histories of antibiotic exposure during the month prior to onset of candidemia. They found that previous exposure to four antibiotic drugs or drug classes increased the risk of infection with fluconazole-resistant Candida nearly three-fold.

"A striking feature of the current cohort of patients with candidemia is the almost universal exposure to antibacterial drugs in the preceding month," the researchers write. "Moreover, the majority of patients received multiple classes of antibacterials, either concomitantly or sequentially."

"Our findings underscore the importance of limiting the use of antibiotics to those situations where these drugs are strictly indicated," says Ben-Ami. He further recommends that clinicians treating patients with candidemia should take the patient's recent antibiotic exposure history into account when selecting the antifungal treatment. "Clinicians should be aware that patients who have recently been treated with certain antibiotics are at increased risk of infection with drug-resistant candida, which in turn could lead to treatment failure," he says. "Previous research has shown that around one third of antibiotic prescriptions are unnecessary."

(R. Ben-Ami, K. Olshtain-Pops, M. Giladi, et al. for the Israeli Candidemia Study Group, 2012. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bnloodstream infection. Antim. Agents Chemother. 56:2518-2523.)

Download a copy of the journal article at: http://bit.ly/asm052112d

###

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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