Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens

Despite the wide availability of antibiotics, infectious diseases remain a leading cause of death worldwide1. In the absence of new therapies, mortality rates due to untreatable infections are predicted to rise more than tenfold by 2050. Natural products (NPs) made by cultured bacteria have been a major source of clinically useful antibiotics. In spite of decades of productivity, the use of bacteria in the search for new antibiotics was largely abandoned due to high rediscovery rates2,3. As only a fraction of bacterial diversity is regularly cultivated in the laboratory and just a fraction of the chemistries encoded by cultured bacteria are detected in fermentation experiments, most bacterial NPs remain hidden in the global microbiome. In an effort to access these hidden NPs, we have developed a culture-independent NP discovery platform that involves sequencing, bioinformatic analysis and heterologous expression of biosynthetic gene clusters captured on DNA extracted from environmental samples. Here, we describe the application of this platform to the discovery of the malacidins, a distinctive class of antibiotics that are commonly encoded in soil microbiomes but have never been reported in culture-based NP discovery efforts. The malacidins are active against multidrug-resistant pathogens, sterilize methicillin-resistant Staphylococcus aureus skin infections in an animal wound model and did not select for resistance under our laboratory conditions.

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More than 200 international attendees are already registered for Phage Therapy & Antibiotic Resistance 2018

The 5th World Congress on Targeting Infectious Diseases – Phage Therapy & Antibiotic Resistance will gather more than 200 international attendees coming from industries, start-up and universities working on all infectious diseases related fields.
The audience of Phage Therapy 2018 will be composed by attendees coming from all around the world. Among the participants:
Queen’s University Belfast
Université Libre de Bruxelles
Eliava Institute of Bacteriophages, Microbiology and Virology
SNIPR biome
Kyorin University
University of Primorska, Faculty of Health Sciences
Universidad Nacional Autonoma de Mexico
University of Lausanne
Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale”
Max Delbrueck Center for Molecular Medicine
Charite University Medicine / Deutsches Rheuma-Forschungszentrum Berlin
G.N. Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology
University of Verona
Lund University
Comsats institute of information technology, Islamabad Pakistan
Polytechnic University of Marche
Institut de Recherche Biomédicale des Armées
G. Eliava Institute of Bacteriophages, Microbiology and Virology
Institut de Recherche Biomédicale des Armées
Jichi Medical University
Central University of Rajasthan
Institute of Microbiology, Norwegian Armed Forces Joint Medical Services
Astellas Pharma Inc
The University of Chicago
Rakuno Gakuen Univ.
university of Naples Federico II
EA Pharma Co.,Ltd.
Rakuno Gakuen University
Clemson University
York University
ITESM – ITE430714KI0
Loughborough University
University of Bath
Clean Cells
Biophage Pharma SA
APC Microbiome Ireland, University College Cork
Yale University
The University of Adelaide
Cellabs Pty Ltd
Gothenburg University
University of Gothenburg
Dopharma Research
University of Alabama
Jichi Medical University
Sree Balaji Medical College and Hospital, BIHER-Bharath University
Fudan University
PTC Phage Technology Center GmbH

Loughborough University
University of California
Korea Advanced Institute of Science and Technology
University of Lausanne
Beiersdorf AG
University of Warwick

Sandia National Laboratories
Masaryk University
Institut Cochin
University of Roma Tor Vergata
Fudan University
University of Brighton
University of Florence
National Infections Service
Public Health England
Tufts University
Università degli Studi di Milano
University Zürich
Snipr Biome
Military Institute of Hygiene and Epidemiology
Hacettepe University
University of Bielefeld
Faculté de Médecine Sorbonne Université
Charles University
Karolinska Institutet
University of Padova
Department of ophthalmology, Kochi Medical School
University of Vienna
Centre of Excellence for Biosensors, Instrumentation and Process Control
Hankuk University of Foreign Studies
N. Lopatkin Institute of Urology and Interventional radiology
The Queen’s University of Belfast
University of Copenhagen
University of applied sciences of Southern Switzerland
SUPSI – Laboratorio Microbiologia Applicata
Masaryk University
Yale University
Institute of Theoretical and Experimental Biophysics
Russian Academy of Sciences
Phico Therapeutics Limited
University of Wisconsin-Madison
Naval Medical Research Center
University of Ferrara
University of Patras
University of Liege – ULg – Gembloux Agro-Bio Tech
Norwegian University of Life Sciences
University of Lausanne
Emergent Biosolutions
Bose Institute

NYU School of Medicine
University of Nottingham
Tel Aviv University
Hebrew University
Erasmus Medical Center
University of Bern
Institute for Infectious Diseases
University of Utah
Uppsala University
University College London
École polytechnique de Montréal Department of Biomedical Engineering
Kyorin University Shcool of Medicine
Department of Biotechnology
Norwegian Institute of Public Health
Wageningen University
Univerisity of Florence
Université Libre de Bruxelles
Queen Astrid Military Hospital, Burn Wound Centre
Latrobe University
Universidade de Santiago de Compostela
National Laboratory for Health, Environment and Food Maribor SI19651295
Cell Biology and Immunology Group
RWTH Aachen University
Universidade Federal de Minas Gerais
Medical University of Gdansk
Kochi Medical School
Institute of Biochemistry and Biophisics of the Polish Academy of Sciences
Vrije Universiteit Brussel
University of Warsaw
University of Bern
Masaryk University
Azti Tecnalia
CEB – University of Minho
University of Siena
Charité – Universitätsmedizin Berlin
University of Wroclaw
Kyorin University
College of Medicine
Alnahrain University
University of Freiburg
Guild BioSciences
JSC “SIC”Microgen”
Vésale Pharma
Beiersdorf AG
BiomX Ltd.
Phico Therapeutics Ltd
MB Pharma
Animal & Plant Health Agency
MaaT Pharma
and many more…

It is a non-exhaustive list of attendees, and we remind you that you can join all these leaders and save if you register before April 17, midnight by clicking here.
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Special Session for Industrials: Showcase your Innovations & Perspectives

You are academic or start-up and you have an extraordinary innovation concerning Phage Therapy?

You are industrial and you are looking for a new academic collaboration to develop innovations around Phage?

A special session B to B  will be organized during the 5th World congress on Targeting Infectious Diseases which will be held  on May 17 – 18, 2018 – Florence, Italy.

Please complete the form here if you are interested to take part and we will organize a meeting with the appropriate person during Phage Therapy 2018 Congress.

Special Session  dedicated to industrials

The third session of the congress is dedicated only to industrials (pharma companies, start-ups, biotech) to present their innovations and perspectives.

Please don’t hesitate to send us an email if you are interested to give a presentation in this session.

To register to Phage Therapy 2018, please follow this link.

Who is attending Phage Therapy 2018 meeting ?

AiCuris, Beiersdorf AG, BiomX Ltd., Davolterra, Emergent, Biosolutions, Guild BioSciences, JAFRAL, JSC “SIC”Microgen”, UPMC, Vrije Universiteit Brussel, University of Warsaw, University of Bern, Azti Tecnalia, University of Siena, University of Tor Vergata, Phico Therapeutics Ltd, Charité – Universitätsmedizin Berlin, Queen’s University Belfast ,University of Wroclaw, INSERM – Institut Cochin, Vésale Pharma, Beiersdorf AG… and more

To know more about complete list of attendees, please follow this link

Phages are an effective alternative to the use of antibiotics in aquaculture

Therapy with phages, instead of antibiotics, is a highly promising option in aquaculture to control the transfer of bacteria that cause important losses or which may be harmful to consumers. Use of these organisms, which infect and destroy bacteria, would significantly reduce the environmental impact of fish farms, whilst increasing their profitability by lowering mortality in the early stages of the breeding process.

These results emerge from the LIFE13 ENV/ES/001048-ENVIPHAGE European project, coordinated by AZTI, in which researchers from Biopolis S.L. (Spain), University of Aveiro (Portugal) and the Aguacircia Aquaculture company (Portugal) have also participated. The project has evaluated the impact of the use of bacteriophages which fight the pathogens responsible for the diseases that affect species bred in fish farms, on the environmental and intestinal bacteria communities of the fish.

Use of natural bacteriophages, which do not affect the health of fish or that of consumers, becomes an interesting alternative to the use of antibiotics. Different research projects had obtained very promising results at laboratory level, but before being able to use bacteriophages at an industrial level, it was necessary to know about the impact of their use on the environment and the marine ecology.

The Enviphage project has sought to address this gap between the laboratory and industrial-scale treatment. In the search for a strategy that enables the health of the aquaculture fish to be improved without affecting the environment or consumer safety, this project has worked on the identification of phages that infect and eliminate the pathogens of interest without affecting the environmental and intestinal bacteria communities, two of the critical points for the use of this technology in fish farms.

Throughout the Enviphage project, the most promising bacteriophages with specific action against the pathogens of relevant fish have been selected for their use on a real scale. Later, following their production on an industrial scale, the phages were applied in fish farms. Their effectiveness has been proven in real conditions and the impact of phage treatment on fish has been evaluated through veterinary monitoring, and on the marine and intestinal bacteria communities through mass sequencing technologies and bacterial ecology studies.

The results obtained during 2017 show that the bacteria community of the intestinal tract of the fish is not significantly affected following treatment with the selected phages. It has also been shown that this treatment does not modify the marine bacteria population in the tanks on the fish farm or in the river where the fish farm is located, so it has zero impact or very limited impact on the bacterial ecology.

Bacteria resistant to antibiotics

Aquaculture is the world’s fastest growing food production sector, with an evident social and economic impact. Aquaculture is a complementary activity to fishing, which provides over 50% of the world’s supply of fish and seafood.

However, the aquaculture sector also faces problems derived from the development and rapid transfer of bacterial infections in the fish farms. The most common treatment to prevent such infections and reduce the corresponding heavy economic losses is the use of antibiotics.

However, in spite of the fact that the health authorities have called for responsible use of antibiotics, their prolonged use in aquaculture has led to the development of resistant bacteria. On the other hand, many of these antibiotics are non-specific, acting not only against the problematic pathogen, but also against other bacteria naturally present in the environment. All of this, together with the consumer call for antibiotic-free products, has led to the search for alternative solutions to the use of antibiotics to fight bacterial infections, particularly in the early stages.

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Developing phage therapy for lung infections

Dr. Sandra-Maria Wienhold, from Charité – Universitätsmedizin Berlin, Germany will talk about “Bacteriophage therapy for lung infections: recent scientific advances”  during Targeting Phage & Antibiotic Resistance Congress which will be held at October 2 – 3, 2017 at Florence, Italy.

Dr. Sandra-Maria Wienhold, veterinarian and researcher in Prof. Martin Witzenrath´s lab ( at the Charité Universitätsmedizin Berlin, dedicates her scientific work to the development of novel therapeutic options for lung diseases, including pneumonia and ventilator induced lung injury. Using experimental in vitro, ex vivo and in vivo techniques the Witzenrath Lab aims at translating novel achievements of basic science into clinical perspectives. One of the current projects aims at providing scientific evidence for the use of bacteriophages produced under GMP conditions against multiresistent gramnegative bacteria. Preclinical evaluations are under investigation and clinical studies will be performed.


Development of Infection-responsive surface coatings for bacteriophage delivery in the catheterised urinary tract: strategic presentation of Targeting Phage & Antibiotic Resistance Conference

During Targeting Phage & Antibiotic Resistance Conference 2017, Dr Nzakizwanayo from School of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom will talk about “Development of Infection-responsive surface coatings for bacteriophage delivery in the catheterised urinary tract”.

According to Dr Nzakizwanayo: “Indwelling urethral catheters (IUC) are widely used for long-term bladder management but are often complicated by acquisition of infection. Proteus mirabilis is a particular problem in this regard, and forms extensive crystalline biofilms on catheter surfaces that obstruct urine flow and lead to serious complications such as pyelonephritis, septicaemia and shock. To address this clinical need, we have developed a novel infection-responsive surface coating for urinary catheters, which responds to elevated pH indicative of P. mirabilis infection. We demonstrate the ability of this coating to provide both a visual early warning of infection, and deliver a therapeutic dose of bacteriophage to control catheter blockage. This potentially “theranostic” coating system is a promising strategy for the deployment of phage therapy and other relevant antimicrobial compounds at local sites within the urinary tract at the exact time when the intervention is needed.”

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Pr Brian Jones will present his study on “Control of catheter associated biofilms through efflux inhibition”

Pr Brian Jones, from school of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom will present his study on “Control of catheter associated biofilms through efflux inhibition“.

According to him: “Proteus mirabilis poses particular problems in the care of individuals undergoing long-term urethral catheterization. This organism forms extensive crystalline biofilm structures on catheter surfaces that block urine flow, leading to serious complications such as pyelonephritis, septicemia and shock. We have previously shown that efflux systems are important for P. mirabilis biofilm formation on catheters, and mutants defective in particular systems are less able to block catheters, highlighting potential therapeutic targets. Subsequently, we screened a range of existing drugs already used in human medicine to identify potential efflux pump inhibitors (EPIs). Molecular modelling indicated selected EPIs showed strong interaction with efflux systems related to biofilm formation, and these compounds were also able to attenuate P. mirabilis biofilm formation and catheter blockage in laboratory models of catheter associated UTI. Overall this suggest efflux inhibition may be a valid approach to control catheter blockage, and existing medicines have the potential to be repurposed for control of bacterial biofilm formation.”

How to use lytic bacteriophages in the treatment of biofilm-forming bacteria involved in prosthetic joint infections?

Dr. Mariagrazia Di Luca from the Charité – Universitätsmedizin Berlin Hospital, Berlin, Germany was invited to give a presentation during Florence Targeting Phage & Antibiotic Resistance Congress 2017. Her presentation will present the role of the lytic bacteriophages in the treatment of biofilm-forming bacteria involved in prosthetic joint infections.

According to Dr Di Luca, the infections involving medical implants represent a unique challenge due to the formation of biofilm in which bacteria are up to a thousand times more resistant to antibiotics than their planktonic counterparts. Lytic bacteriophages, when active against biofilms, represent a promising treatment, particularly against drug resistant bacteria. 

The present communication will focus on the anti-biofilm activity of both commercially available and newly isolated bacteriophages against bacterial strains relevant in the context of prosthetic joint infection.

For more information about Dr Di Luca, please click here.

New Antibiotic Resistance Genes Found in Soil Microbes

Farm soil harbors abundant genes related to antibiotic resistance in microbes, including some that have never been identified in human pathogens, according to a study published Friday (June 16) in Applied and Environmental Microbiology. Researchers identified novel gene products, including peptides and enzymes, that can provide resistance to classes of antibiotics used to combat a range of bacterial infections, including those that cause strep throat and chlamydia.

“There are certainly, in the environment, cryptic antibiotic resistance genes that have yet to be transferred to human pathogens,” study coauthor Edward Topp, an environmental scientist at University of Western Ontario, London, and also Agriculture and Agri-Food Canada, tells The Scientist in an email.

Topp and colleagues collected soil samples from farm plots in London, Canada, that the team had exposed to antibiotics for up to 16 years. The researchers extracted DNA from the samples, then cloned fragments of specific sequences into a strain of E. coli sensitive to antibiotics. When the researchers put the altered E. coli in petri dishes with various antibiotics, they saw some colonies were able to grow, indicating the transfected DNA fragments conferred resistance. Through sequencing, they identified 34 new antibiotic resistance genes.

“The particularly surprising result is the discovery of a gene that encodes for an unusual small proline-rich polypeptide that confers resistance to the macrolide antibiotics, very important in human and animal medicine,” Topp says. Macrolide antibiotics are used to treat strep throat and pneumonia, as well as chlamydia and syphilis. The mechanism by which the newly identified gene confers resistance to macrolide antibiotics is not yet known.

With advanced genomic techniques, studies such as Topp’s are helping researchers understand the diversity of resistance compounds in the environment, says bacterial epidemiologist Kimberly Cook of the United States Department of Agriculture. “What we are learning is that the genes that confer resistance are wide ranging and the mechanisms for resistance are even wider ranging than previously thought,” says Cook, who was not involved in the current study.

Microbiologist Rafael Cantón of the Ramón y Cajal Institute for Health Research in Madrid notes that antibiotic resistance genes are naturally present in soil bacteria, and some may work in ways not yet identified in clinical bacteria. “If we understand these resistance mechanisms, we can search for new antibiotics that might not be affected for these mechanisms,” he says in an email to The Scientist.

Indeed, natural environments may serve as hotspots for the evolution of antibiotic resistance, Topp and colleagues write in their study. Farmland, for instance, is exposed to antibiotics by the spread of manure from chicken, pigs, and other livestock, which are often given antibiotics to maintain their health. Human waste, also used as fertilizer, can contain antibiotics as well. A growing number of studies suggest that such dumping animal and human waste and other anthropogenic activities are increasing the abundance of antibiotic resistance genes in the environment, though it’s not clear if pathogens can recruit antibiotic resistance genes through horizontal gene transfer from the environment.

The best way to ensure pathogens can’t recruit antibiotic resistance genes from the environment is by not putting them there in the first place, Topp notes. He suggests a push for continued reduction of antibiotic use in food animal production through regulatory and economic measures, which would reduce the amount of antibiotics that enter into the agricultural system through the spread of manure.

“This is very clear,” writes Cantón. “If we reduce the presence of antibiotics in the environment, we will reduce selection of resistant bacteria. Antibiotics kill or inhibit susceptible bacteria but not resistant ones. Hence, overload of antibiotics in the environment enriches resistant populations.”

C. Lau et al., “Novel antibiotic resistance determinants from agricultural soil exposed to antibiotics widely used in human medicine and animal farming,” Applied and Environmental Microbiology, doi:10.1128/AEM.00989-17, 2017.

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New generations of antibiotics for MDR pathogens from old antibiotic classes and new resistance breaker

Prof. Gian Maria Rossolini from University of Florence, Italy will participate to Targeting Antibiotic Resistance 2017 Congress and will talk about his research on “New generations of antibiotics for MDR pathogens from old antibiotic classes and new resistance breaker”.

According to Prof. Rossolini: “The modification of old antibiotic scaffolds and the combination of old antibiotics with new resistance breakers (e. g. beta-lactamase inhibitors) have proved among the most successful strategies to combat antibiotic resistance in the short/medium-term range. This presentation will focus on how these strategies are now providing us with new powerful antibiotics for MDR pathogens, and on which are the challenges encountered with these new agents”.

If you would like to know more, please register to Targeting Antibiotic Resistance 2017 on