News

Novel antibiotic resistance gene in milk

Global

Researchers at the University of Bern have identified a new antibiotic resistance gene in Macrococcus caseolyticus strains from dairy cows. This gene confers resistance to all beta-lactam antibiotics including the last generation of cephalosporins used against methicillin-resistant Staphylococcus aureus (MRSA). A transfer to S. aureus (which is possible according to the researchers) would jeopardize the use of reserve antibiotics to treat human infections caused by multidrug-resistant bacteria in hospitals.

Macrococcus caseolyticus is a harmless bacterium naturally found on the skin of dairy cows which can spread to milk during the milking process. It can also be present in dairy products made from raw milk.

The researchers investigated M. caseolyticus present in milk of dairy cows suffering from mastitis. These strains showed an unusual resistance pattern to beta-lactam antibiotics with a resistance profile resembling that of MRSA, but the known genes responsible for resistance (mecA, mecB and mecC) were missing. Using Next Generation Sequencing (NGS), the researchers rapidly found that the M. caseolyticus isolates acquired a novel antibiotic resistance island which contains a new methicillin resistance gene designated mecD. This discovery is published in Scientific Reports.

The researchers demonstrated that the novel methicillin resistance gene mecD confers resistance to all classes of β-lactams including anti-MRSA cephalosporins. It was located on a resistance island which has been acquired by M. caseolyticus. Further experimental investigations of the resistance island showed that it also has the potential for integration into the chromosome of S. aureus.

M. caseolyticus containing the novel mecD gene has been so far mainly found in cattle, but in one case it has been isolated from skin infection in a dog indicating that this bacterium has the potential to colonize different animal species.

Read article: Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources by Sybille Schwendener, Kerstin Cotting and Vincent Perreten, published in Scientific Reports (2017) 7, article number: 43797, doi:10.1038/srep43797

[SOURCE: University of Bern]

Unique structure of ASFV enzyme may allow drug development

Global

A DNA-copying protein from African swine fever virus (ASFV) has a unique structure that may offer a target for drugs, according to a study published in PLoS Biology by Yiqing Chen and colleagues at Fudan University in Shanghai, China.

Viral replication depends in part on a polymerase enzyme, AsfvPolX, that repairs breaks in the DNA, but the structure of this enzyme has not been determined in detail. The authors used X-ray diffraction and nuclear magnetic resonance to solve the structure at atomic resolution.

The team found that the enzyme contained a unique binding pocket for the building blocks of DNA (nucleotides), not seen in related enzymes in other organisms. They also found several other unique structural features, including a pair of hydrophobic amino acids that interact with incoming nucleotides, and a “platform” created by two basic amino acids that stabilizes a mismatched nucleotide pair, increasing the rate of incorporation of erroneous nucleotides into the DNA chain during the repair process. Together, these features give the polymerase its unique character of a high rate of DNA replication combined with a high copying error rate.

Blocking the binding pocket with a drug may be a valuable strategy to treat ASFV infection, the authors suggest. “Exploiting this unique structural feature to attack the virus may offer a rapid route to develop treatments for this important agricultural virus,” says Chen, although he noted one caveat; the high error rate of the AsfvPolX polymerase enzyme means that the virus mutates rapidly, and therefore may evolve resistance to drugs designed to block it.

Read article: Unique 5′-P recognition and basis for dG:dGTP misincorporation of ASFV DNA polymerase X by Yiqing Chen, Jing Zhang, Hehua Liu, Yanqing Gao, Xuhang Li, Lina Zheng, Ruixue Cui, Qingqing Yao, Liang Rong, Jixi Li, Zhen Huang, Jinbiao Ma and Jianhua Gan, published in PLoS Biology (2017)15(2): e1002599, doi:10.1371/journal.pbio.1002599

[SOURCE: PLOS]

Gene editing for PRRSV resistance in pigs

Global

Precision engineering renders target cells of PRRSV resistant to infection with the virus.

Researchers have used advanced genetic techniques to produce pigs that are potentially resilient to Porcine reproductive and respiratory syndrome (PRRS).

Early tests have revealed that cells from the pigs are completely resistant to infection with both major subtypes of the virus that causes the disease. The animals are otherwise healthy and the change – introduced using gene editing technology – should not affect their ability to fight off other infections, the researchers say.

Studies have shown that the PRRS virus targets macrophages. A molecule on the surface of these cells called CD163 plays a key role in enabling the PRRS virus to establish an infection. The research team at the University of Edinburgh’s Roslin Institute, in collaboration with Genus, used a gene-editing tool called CRISPR/Cas9 to cut out a small section of the CD163 gene in the pigs’ DNA code.

Laboratory tests of cells from the pigs with the modified CD163 gene have confirmed that this change in the pig’s DNA blocks the virus from being able to cause infection. The next stage in the study will be to test whether the pigs are resistant to infection when exposed to the virus. The findings are reported in PLoS Pathogens.

“Genome-editing offers opportunities to boost food security by reducing waste and losses from infectious diseases, as well as improving animal welfare by reducing the burden of disease. Our results take us closer to realising these benefits and specifically address the most important infectious disease problem for the pig industry worldwide,” said Professor Alan Archibald, Head of Genetics and Genomics, The Roslin Institute

Previous studies by another team have produced pigs that lack the entire CD163 molecule, and which do not become ill when exposed to the PRRS virus. In the latest study, only the section of CD163 that interacts with the PRRS virus is removed and the molecule appears to retain its other functions.

PRRS is endemic in most pig producing countries worldwide. Vaccines have mostly failed to stop the spread of the virus, which continues to evolve rapidly. It is one of the greatest challenges facing pig producers today. In Europe alone, the disease is estimated to cost the pig industry more than €1.5 billion each year.

Article: Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function by Christine Burkard, Simon G. Lillico, Elizabeth Reid, Ben Jackson, Alan J. Mileham, Tahar Ait-Ali, C. Bruce A. Whitelaw and Alan L. Archibald, published in PLoS Pathogens (2017) 13(2): e1006206, doi:10.1371/journal.ppat.1006206

[SOURCE: UNIVERSITY OF EDINBURGH]

Call for Interest on Designation as FAO Reference Centre for Antimicrobial Resistance (AMR)

Global

Members of the Food and Agriculture Organization (FAO) committed at the 39th Session of the FAO Conference (June 2015) to work on the issue of Antimicrobial Resistance (AMR) through Resolution 4/2015. The resolution calls upon both FAO members and the organization itself to address the threat posed by AMR to public health, agriculture production and food safety and security. The FAO Resolution on AMR highlights the support of the food and agriculture sector to implement the Global Action Plan (GAP) on AMR which was developed by the World Health Organization in collaboration with FAO and the World Organisation for Animal Health. In 2016, the FAO Action Plan on Antimicrobial Resistance 2016 – 2020 was developed and published outlining the role of FAO on implementing the GAP.

Four focus areas were identified in the FAO Action Plan on AMR: 1) improving awareness on AMR and related threats, 2) developing capacity for surveillance and monitoring of AMR and antimicrobial use (AMU) in food and agriculture, 3) strengthening governance related to AMU and AMR in food and agriculture and 4) promoting good practices in food and agriculture systems and the prudent use of antimicrobials.

FAO is seeking suitable institutions that are interested in being designated as Reference Centres for AMR to support FAO and their member countries in the implementation of the activities outlined in the FAO Action Plan.

As per the Director-General’s Bulletin 2006/32, FAO Reference Centres (RCs) are institutions designated by the Director-General to provide independent technical and scientific advice on issues related to FAO’s mandate and its programme. The institutions to be recommended for designation as a “FAO Reference Centre” should have demonstrated, through previous collaboration with one or more of FAO’s technical units, the following:

• Active engagement in fields of expertise relevant to the work of the Organization and contribution to the implementation of its programme priorities and to strengthening capacities in countries and regions;
• Ability to carry out one or several of the following functions:
o Standardization of technology, therapeutic and other substances, and of methods/procedures;
o Provision of reference materials and services such as quality assurance;
o Participation in collaborative research of a scientific, technical or policy nature;
o Contribution to capacity development inter alia through the provision of training;
o Coordination of activities carried out by other institutions;
o Provision of information and advice of a scientific, technical and policy nature.

As it relates to AMR, the selected FAO RCs would be expected to have a history of collaboration with one or more of FAO’s technical units of at least two years (or less under special circumstances to be justified and demonstrated by the relevant technical unit) and a team of experts in the subject. The RC would be expected to provide the following types of support:
• Provide scientific, technical and policy advice on matters related to AMR
• Conduct training for Member States on AMR issues
• Provide expertise on laboratory capacity and surveillance of AMR, including
o Antimicrobial susceptibility testing methods
o Surveillance system setup
o Data management, interpretation and reporting of AMR data
o Review of national laboratory capacities pertaining to AMR in the authorities responsible for food safety, terrestrial and aquatic animal health, plant protection, or environmental health (use of FAO laboratory AMR assessment tool – ATLASS)
o Provision of reference organisms
o Provision of reagents and organization of a proficiency testing program for susceptibility testing for a selection of priority pathogens, commensals and indicators such as Salmonella, Campylobacter, E. coli, Enterococci, etc
o Method development (scaled to country needs from development and use of standard operating procedures to Next Generation Sequencing, etc)
• Support the global interpretation of compiled AMR data (including indicators, impact measurement, etc)
• Carry out confirmatory testing of resistant isolates and serotypes of particular concern upon request
• Support the quality control of antimicrobials used in the food and agriculture sector
• Participate in collaborative research on AMR

The FAO AMR RC status would be valid for a period of four years. An annual report of the Institution’s support activities related to work as an RC will be required. A renewal of the status as FAO RC is possible depending on the activities undertaken and the value and strength of the collaboration. The designated RC will enjoy name recognition and association with a United Nations agency, including the possibility of using FAO’s name, emblem and other logos under set conditions (as described in Annex 2 of the Director-General’s Bulletin 2006/32).

Should this designation as a FAO Reference Centre be of interest to your institution, being able to use the institution’s own resources to fulfil several of the above listed functions, please refer to the webpages (http://www.fao.org/ag/againfo/partners/en/FAO_Reference_Centres/How_to_apply.html) for information on how to apply. Fill out the “Declaration of Interest” (DG Bulletin 2006/32 Annex 1) and acknowledge the information provided in the “Disclaimer and other legal provisions” (DG Bulletin 2006/32 Annex 3).

Application due date: 15 April 2017

Contact: FAO-AMR-Reference-Centre@fao.org