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The official newsletter for FEMS Affiliates

A F F I L I AT E S L E T T E RJUNE 2014

Also in this issue:

ThemeInterview: Jean Carlet

Publications PageAntibiotic resistance research

Grants CornerMäkelä – Cassell FEMS-ASM grant

Society FeatureContributions of FEMS member societies regarding antibiotic resistance research

Deadlines

FEMS-Sponsored Meetings

Microbiology TidBits

A MiniReview from FEMS Yeast Re-search deals with new genetic tools for Hansenula polymorpha that can be used for biotechnological produc-tion of antibiotics. A MiniReview pub-lished in FEMS Microbiology Letters describes resistance to antimicrobial peptides in Gram-negative bacteria. The editorial by Klenk, Ron, Sansonet-ti and Tonjum published in the recent Pathogens and Disease Special Issue Biofilms III highlights the synergies of microorganisms especially in bio-films, and describes convergent ap-proaches to delineate co-infections. This is an important contribution by a number of top scientists. From FEMS Microbiology Ecology a nice review has been selected on the global geography of Streptomyces antibiotic inhibition, resistance and resource use. Finally, there are a few additional contributions, for instance a research paper on the abundance and trans-ferability of antibiotic resistance to sulfadiazine in maize rhizospere and bulk soil.

Especially, I like to draw your atten-tion to an interview with Jean Carlet. In recent years he has been the medi-cal director and head of the Research and Safety programme at the French Authority for Health, and he was a consultant for the World Health Or-ganization (WHO). He is an important person for the WAAAR, the World Al-liance Against Antibiotic resistance.

This is one of several global initiative to safeguarding antibiotics and to raise the public awareness. Together with numerous organizations and individual researches he developed a declaration that can be used to present to politicians and authorities, health care organizations, etc. and raise public awareness.

Please take notice, read the information and the declaration, and act, whenever and wherever you can!

Act, whenever and wherever you can!

Editorial by Prof. Bauke Oudega, FEMS Vice-President

One of the most important and dramatic devel-opments of this time is antibiotic resistance and the appearance of multi-drug resistant bacteria. The pipeline for new antibiotics is almost dry for the next five years. The impact on human health systems in the near future is potentially huge. The resistance is mainly due to the excessive use of antibiotics in all sectors. This issue focuses on this phenomenon. From all FEMS Journals, reviews or papers were selected that highlight several aspects of antibiotic resistance develop-ment.

Some bacteria are more resistant to drugs than others. Occasion-

ally these resilient strains survive, multiply and become more resistant to antibiotics. This is how superbugs

such as MRSA have evolved.

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P U B L I C AT I O N S PA G E

Jean Carlet: antibiotics must

really be protected

Telephone interview with Prof. Jean Carlet, 16 June 2014, a week before the release of the WAAAR Declaration on Monday 23 June 2014.

Antibiotic resistance as a part of nature will always exist. Why did it become dangerous over the last couple of years?It became dangerous because it is increasing, particularly in the developed countries. Consider for example that enterobacteriacae like E. coli, a microorganism that lives in humans, are being resistant in particular to 3rd generation cephalo-sporines which were always active ten years ago, that some enterobacteria are now resistant to Carbapenems, the last running group of antibiot-ics active - in some strains, the only one.

The second reason is because there are very few new antibiotics, very few new mechanisms of action. So the problem consists of increasing resistance and decreasing antibiotics. We have reason to be afraid.

What do we need if we want to at least moderate this development?The reason why the resistance is increasing is mostly the over-usage of antibiotics. We use a lot of antibiotics for infections which do not require

any antibiotic. This could be different from one country to another. Forty percent of the use of antibiotics is unnecessary. The idea is to try to decrease antibiotic consumption with a lot of different measures (antibiotic stewardship), but also a fight against cross-transmission. The pro-cess of resistance happens in two steps: the first is acquisition of the selection of resistance by the antibiotics - the second step is that we are cross-transmitting strains between patients, sometimes between animals and patients. Hand washing and also control measures are very important.

Antibiotics are used in a lot of animals, particu-larly fish, and in agriculture. The problem is that in many countries the antibiotics are still used as growth factors. In fact 70 – 80 % of all antibiotics used are given to animals, not humans. Therefore, we are trying to convince veterinarians to de-crease antibiotics consumption in animals.

What is the most important message you wish to bring to the public?I think the most important is to try to convince people that antibiotics must really be protected, because they are in danger. They saved a lot of lives since their discovery. Antibiotics are not a

Guard yourself!

• Don’t get infected if you can prevent it. Prepare your meat hygienically: cook it well so all bacteria die. Thoroughly wash and clean utensils after handling raw food that can be contaminated, such as chicken. Also wash your hands with soap and water afterwards.

• Buy smart: check if the producers of the food you buy (ab)use antibiotics as growth measure or to prevent in stead of cure diseases.

• Use antibiotics only when absolutely necessary and if on prescription.

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P U B L I C AT I O N S PA G E

WAAAR declaration focuses on: 1. making all stakeholders aware2. organization of a financed national plan

for the containment of antibiotic resist-ance in each country

3. continuous access to antibiotics of as-sured quality, especially in middle and low income countries

4. integrated surveillance of antibiotic resistance and antibiotic use

5. use of diagnostic tests6. antibiotic stewardship (prudent, con-

trolled and monitored approaches to the use of antibiotics)

7. educational efforts for change8. containment of bacterial transmission

and prevention of infection9. basic and applied research, and devel-

opment of new antibiotics10. request for UNESCO to include the

antibiotics in the list of the intangible cultural heritage.

Download the full PDF file:

trivial act; they differ from other drugs because microorganisms are living targets.Before 1928 people would die of infections, could you imagine that age could return?It could happen if the situation is not moving from now. Of course people will try to find new antibi-otics. Companies will discover and develop anti-biotics, but this is so expensive that some compa-nies are not interested at all. So we need to have them take different measures. While the price of the drug is very high as compared to ordinary drugs, you can imagine when a very interesting spectrum is developed it would still benefit a com-pany. We will probably have new antibiotics in the next few years, some may prevent us going back to the pre-antibiotic era.

Suppose a reader of FAL reads this interview and thinks he or she wants to act against antibiotic resist-ance. What can they do?They can consider that it’s some kind of crusade against antibiotic resistance. They can, as micro-biologists, become active in the field of research on antibiotic resistance. They can try to convince others, medical doctors and they can themselves improve their own ways of using antibiotics. They can try to be at the head of the crusade.

Our WAAAR declaration is supported by many societies including large US societies, many peo-ple have signed the declaration. We will continue to work with the societies, certainly try to find new societies to support us. The members of the socie-ties will hopefully be informed by the executive committee of the society by their websites.

OUT NOW: VIRTUAL ISSUEVISUALIZING MICROBES FROM MOLECULES TO CELLS

Start your own campaign with these tools:

• WAAAR - World Alliance of Awareness of Antibiotic Resistance• Antibiotic Awareness - governmental education tools (UK)• ECDC - governmental education tools (Canada)

VOTE #antibiotics on:• Longitude Prize, a £10 million prize fund to help solve one of the greatest issues of our time. • My World (UN) - A global vote at the United Nations, allowing people to have a direct say in

defining the next global agenda to address extreme poverty and preserve the planet. Note: antibiotic resistance is not in the prefix, but you can suggest it as a priority.

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P U B L I C AT I O N S PA G E

Antibiotic resistance research

- part IFEMS Microbiology Reviews

Research article

Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria The continuous dissemination of ‘multidrug-resistant’ (MDR) bacteria drastically reduces the efficacy of our antibiotic ‘arsenal’ and consequent-ly increases the frequency of therapeutic failure. Recent investigation on the efflux pump AcrB at its structural and physiological levels, may pave the way towards the rational development of an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms.

Nikaido et al.DOI: 10.1111/j.1574-6976.2011.00290.x/abstract

FEMS Microbiology Letters MiniReview

Resistance to antimicrobial peptides in Gram-negative bacteriaAntimicrobial peptides (AMPs) are microbicidal and have also been shown to act as immunomod-ulators with chemoattractant and signalling activities. During the co-evolution of hosts and bacterial pathogens, bacteria have developed the ability to sense and initiate an adaptive response to AMPs to resist their bactericidal activity. This article offers a review of the various mechanisms used by Gram-negative bacteria to sense and re-sist AMP-mediated killing. These mechanisms play an important role in bacterial resistance to host-derived AMPs. Bacterial resistance to AMPs should also be taken into consideration in the develop-ment and use of AMPs as anti-infective agents.

Gruenheid and Le MoualDOI:: 10.1111/j.1574-6968.2012.02528.x/abstract

FEMS Yeast Research MiniReview

Novel genetic tools for Hansenula polymorphaThis article presents an overview of key compo-nents of the genetic toolbox for H. polymorpha in-cluding new selection markers. It describes novel strategies for the efficient creation of targeted gene deletions and integrations in H. polymorpha and shows the implementation of Gateway tech-nology and a single-step PCR strategy to create deletions in H. polymorpha. All PEN biosynthetic enzymes were satisfactory produced and allowed production of the antibiotic penicillin G, which was efficiently secreted into the culture medium.

Saraya et al.DOI: 10.1111/j.1567-1364.2011.00772.x/full

Pathogens and Disease MiniReview

Acinetobacter baumannii: evolution of a global pathogenAcinetobacter baumannii is an opportunistic nosocomial pathogen and one of the six most important multidrug-resistant microorganisms in hospitals worldwide. Mortality rates can reach 35%. The recent expansion of A. baumannii se-quenced genomes has permitted the develop-ment of large-array phylogenomic and pheno-typic analyses, which can offer valuable insights into the evolution and adaptation of A. baumannii as a human pathogen. This review summarises these recent advances and proposes new avenues of research.

Antunes, Visca and TownerDOI: 10.1111/2049-632X.12125/abstract

Acinetobacter baumanii

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P U B L I C AT I O N S PA G E

FEMS Microbiology Ecology Research Article

Sulfadiazine in maize rhizosphere and bulk soilVeterinary antibiotics entering agricultural land with manure pose the risk of spreading antibiotic resistance. The fate of sulfadiazine (SDZ) intro-duced via manure and its effect on resistance gene levels in the rhizosphere were compared with that in bulk soil. The accumulated SDZ expo-sure of the bacteria significantly correlated with the log relative abundance of sul1 and sul2, so that these resistance genes were less abundant in the rhizosphere than in bulk soil. Plasmids conferring SDZ resistance, which were exogenously captured in Escherichia coli, mainly belonged to the LowGC group and carried a heterogeneous load of resist-ances to different classes of antibiotics.

Christoph Kopmann et al.DOI: 10.1111/j.1574-6941.2012.01458.x/abstract

Pathogens and DiseaseSpecial Issue

Biofilms III

When pathogens reinforce each other synergistically, dis-ease transmission and progression are enhanced, in synd-emism. Coinfections arise with representa-tives of all classes of microorganisms, bac-teria, viruses, yeast/ fungi, and parasites as well as combinations of these.

Read the latest Special Issue Biofilms III, including: • Antimicrobial Peptides • Toxin-Antitoxin systems• Biofilm models for the food industry• M. tuberculosis phenotypic drug resistance• Pseudomonas aeruginosa• Anti-biofilm agents• Formation of hydroxyl radicals

The highest number of Streptomyces isolates was found in Witzenberg, Germany

FEMS Microbiology Ecology Research Article

Global biogeography of Streptomyces antibiotic inhibition, resistance, and resource useThis work explored geographic variation in Strep-tomyces phenotypes that are critical to species interactions. Streptomyces with near-identical 16S rRNA gene sequences from different locations sometimes differed significantly in inhibition, resistance, and resource use phenotypes, suggest-ing that these phenotypes may be locally adapt-ed. Thus, in addition to a likely role of environmen-tal filtering, variation in Streptomyces inhibitory, resistance, and resource use phenotypes among locations is likely to be a consequence of local selection mediated by species interactions.

Schlatter and KinkelDOI: 10.1111/1574-6941.12307/abstract

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G R A N T S CO R N E R

Shipping up to Boston

Francesca Turroni was the second grantee to receive the Mäkelä – Cassell FEMS-ASM grant - and the first to attend the ASM General meet-ing in Boston, Massachusetts. Next year, the grant will go to an ASM member who will then be able to attend the FEMS Congress and visit a lab on the other side of the ocean in 2015.

About my researchThe human intestine is home of an almost incon-ceivable large number of microorganisms called the human gut microbiota, which can be pictured as an organ placed within a host organism. Within the human gut microbiota, bifidobacteria repre-sent the first most numerous microbial groups encountered in the colon of infants, considerably outnumbering other bacterial groups. Bifidobac-teria are anaerobic, Gram-positive, irregular or branched rod-shaped bacteria that are commonly found in the gastro-intestinal tracts (GIT) of hu-mans and most animal and insects. Despite the generally accepted importance of bifidobacteria as probiotic components of human GIT microflora and their use in health-promoting foods, there is a paucity of data about the molecular background covering their probiotic features (e.g. interaction with the host and with the components of the gut microbiota).

Parts of my research on the genetics underlying microbe-host and the microbe-microbe interac-tions, with particular emphasis on Bifidobacterium genus, have been shown in a poster entitled: “Evaluation of the bifidobacterial microbe-host crosstalk” that has been presented at the last ASM General Meeting at Boston. This poster described the molecular dialogue occurring between dif-ferent bifidobacterial strains during co-coloniza-tion of the murine gut. Furthermore, thanks to metagenomics analyses I was able to evaluate the impact of supplementation of bifidobacteria on the various component of the gut microbiota of mice. These results suggest that there is an inter-active relationship between host and components of the intestinal microbiota and such knowledge increased our understanding of the mechanisms of action of the perceived positive health benefits exploited by bifidobacteria.

Pictures taken at the ASM General Meeting, top left: FEMS President Jean-Claude Piffaretti and Francesca Turroni.

About the ASM General MeetingI was really impressed by the large number of at-tendees and the overall organization of ASM gen-eral Meeting. There were scientific sessions and posters covering all the diverse areas of microbiol-ogy that gave me the opportunities to get a very wide scientific view of what is the current state of knowledge not only in my research topic but also in related fields. I had the opportunity to attend very interesting talks and symposia focusing on Host-Microbe Relationships and Multi-Omics ap-proaches to investigate the Human Gut Microbio-ta. In addition, the poster sessions included about 2800 posters many of them belong to divisions close to those of my interest. My poster attracted a lot of interest from many young scientists work-ing on the gut microbiota and bifidobacteria from research institutes or academia distributed from over the world.

About the Mäkelä-Cassell FEMS-ASM GrantThe possibility to attend the ASM General Meet-ing is a wonderful opportunity to receive the best updated information about every sector of micro-biology as well as to meet scientists and create a network with them. The possibility to view the most innovative instruments and every type of laboratory equipment from the major company is a really good chance to expand my knowledge. I’m really grateful to FEMS, who supported me through the Mäkelä-Cassell Grant that allowed me to join this meeting.

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S O C I E T Y F E AT U R E

Antibiotic resistance research highlights

- part IIYou can tell by the number of meetings and publications that scientists around the world are aware of the urgency of the topic. When we asked our societies to contribute to this letter, we received some very interesting articles.

Society for General Microbiology Microbiology

Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibi-otics Tetracyclines (TCs) are medically important an-tibiotics from the polyketide family of natural

products. Chelocardin (CHD), produced by Amyco-latopsis sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic activity against a number of Gram-positive and Gram-negative multi-resistant pathogens. CHD has an unknown mode of action that is different from TCs. It has some structural features that define it as ‘atypical’ and, notably, is active against tetracycline-resistant pathogens. Identification and charac-terization of the chelocardin biosynthetic gene cluster from A. sulphurea revealed 18 putative open reading frames including a type II polyketide synthase. Compared to typical TCs, the chd clus-ter contains a number of features that relate to its classification as ‘atypical’: an additional gene for a putative two-component cyclase/aromatase that may be responsible for the different aromatization pattern, a gene for a putative aminotransferase for C-4 with the opposite stereochemistry to TCs and a gene for a putative C-9 methylase that is a unique feature of this biosynthetic cluster within the TCs. Collectively, these enzymes deliver a molecule with different aromatization of ring C that results in an unusual planar structure of the TC backbone. This is a likely contributor to its different mode of action. In addition CHD bio-synthesis is primed with acetate, unlike the TCs, which are primed with malonamate, and offers a biosynthetic engineering platform that represents a unique opportunity for efficient generation of novel tetracyclic backbones using combinatorial biosynthesis.

Lukežič et al.Read the full article

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S O C I E T Y F E AT U R E

Revista Societătii Române de MicrobiologieBacteriologia, Virusologia, Parazitologia,

Epidemiologia

Antibiotic resistance aspects in anaerobic bacte-ria involved in abdominal surgery infectionsDespite its huge impact on the surgical and thera-peutic management of gastrointestinal tractinfection, the continuously growing frequency of anaerobic bacteria in surgical infections is still generally not recognized by many surgeons. Due to the prevalence of anaerobic bacteria in colon, surpassing by 1,000 times the number of aerobic bacteria, most anaerobic infections have an en-dogenous origin and are typically polymicrobial. Identification of anaerobic bacteria and further antibiotic susceptibility testing require special methods of sampling, immediate cultivation and direct Gram staining of clinical specimen. Increas-ing antibiotic resistance among anaerobic bacteria has led to intensive studies about the underlying genetic and molecular mechanisms. This paper reviews the antibiotic resistance mechanisms of anaerobic bacteria and the therapeutic manage-ment of the associated gastro-intestinal infections.

Cristina Delcaru, Gabriela Gorzo, Veronica LazărRead the full article

TMC Journal Türk Mikrobiyol Cem Derg

Investigation of plasmid-mediated methylase genes in aminoglycoside resistant gram-nega-tive bacteriaAminoglycosides are an important class of antibi-otics currently used for the treatment of infections caused by both Gram-positive and Gram-negative

bacteria. Increasing resistance to the other anti-microbials as well as aminoglycosides is a serious problem. Plasmid-mediated 16S rRNA methylases are a different mechanism causing high-level re-sistance to aminoglycosides. The aim of this study was to investigate plasmid-mediated 16S rRNA methylases causing high-level aminoglycoside resistance to gram-negative bacteria.

It was suggested that the aminoglycoside resist-ance in these Gram-negative organisms was caused from different methylase genes or the other resistance mechanisms. The similar studies which will be carried out in our country will be of great importance on behalf of monitoring the re-sistance via methyltransferases and inhibiting the spread of the genes encoding these enzymes.

Emertcan et al.Read the abstract

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DEADLINES

4 J U L Y 2 0 1 4 4th Centr. Eur. Summer Course on MycologyHungary

1 2 J U L Y 2 0 1 4 18th European Bioenergetics ConferencePortugal

3 1 A U G U S T 2 0 1 411th Symposium on Lactic Acid Bacteria - Health, Sustainability , Diversity and Applica-tionThe Netherlands

FEMS-Sponsored Meetings, July/August 2014

MICROBIOLOGY TIDBITS

VIDEO: Fighting back against ‘intelligent’ drug-resistant bacteria

Source: Euronews

Bacteria found in squid raise concernResearchers in Canada have discovered one of the deadliest kinds of antibiotic-resistant bac-teria for the first time in a food product — raw squid. The discovery of such a microbe in food means a you may be bringing resistant bacteria into your home rather than acquire them while traveling or following hospitalization.

Source: Washington Post

Achilles heel antibiotic-resistant bacteria found?Scientists have found a new route to attack antibiotic-resistant bacteria by blocking the mechanism they use to build their exterior coat-ing. The bugs construct this defensive barrier in a complex process that depends on a key dual-protein molecule.

Source: BBC

VIDEO: Don’t wash raw chicken

Source: Kettering Borough Council

1 September 2014FEMS Meeting Attendance Grants

1 December 2014FEMS National & Regional

Congresses Grants

1 December 2014FEMS Research Grant