The names of infectious diseases that threaten the health of people worldwide have become part of the common vocabulary: Zika, MRSA (Methicillin-resistant Staphylococcus aureus), Salmonella, N. gonorrhoeae, E. coli O157:H7. New threats emerge regularly, and priority rankings shift. Behind these names are precious materials that commonly support the authentication and verification of these pathogens. These commodities are known as culture collections.
Culture collections, on the surface, do what their name implies: they collect microorganism cultures. These collections are living repositories that, when properly maintained, can provide an invaluable service to education, research, clinical, food, environmental, and industrial applications. Yet ensuring the availability, accessibility, and affordability of the biological reference materials held in these collections can be challenging, which can potentially impede global health solutions.
Culture collection demographics
The World Federation of Culture Collections (WFCC) developed an international database on biological reference materials globally. This World Data Center for Microorganisms, maintained at the National Institute of Genetics in Japan, states that it holds data on the organization, management, and services of 476 culture collections from 62 countries. The WFCC produces guidelines on the optimal operation of a culture collection.
In the United States, culture collections may be held by federal and state government agencies, such as the Centers for Disease Control and Prevention (CDC) and state health departments. Universities may also maintain libraries of biological materials for their research. Independent organizations, such as the American Type Culture Collection, serve as well-known repositories of tens of thousands of cultures.
Collections vary in size and content. Some may contain varieties of bacteria, fungi, yeast, viruses, and protozoa, while others focus on a specific area of scientific interest (e.g., Department of Insect Pathology in the Czech Republic). Still others may collect pathogens of immediate regional interest, as when a new pathogen emerges in one corner of the world and threatens the health of those inhabitants.
Culture collections may be certified to international standards for quality management systems (for example, ISO 9001). They may also be accredited for laboratory testing (as with ISO 17025) or for competence as a reference material provider (e.g., ISO Guide 34). Certification and accreditation are not mandatory.
The need for reference material availability
Biological materials from culture collections are used to ensure the authenticity, validity, and relevance of laboratory testing. Whether a laboratory needs to confirm the presence of Vibrio parahaemolyticus in seafood or test drug resistance to Mycobacterium tuberculosis in a compromised patient, it is imperative for the testing material to be reliable and accurate. Public Health England, which is the custodian of four culture collections, posts: “Authenticated reference strains are of paramount importance for clinical diagnostic testing, food, water, and environmental microbiology testing, and validation studies.”
Yet, despite the need, these reference materials are not always available. Take, for example, a federal policy directive issued in September 2011. The USDA Food Safety and Inspection Service announced it would implement routine verification testing for six Shiga toxin-producing E. coli (STEC), in addition to the more prevalent E. coli O157:H7, in raw beef manufacturing trimmings. The directive stated that on June 4, 2012, raw, non-intact beef products or their components containing the STEC strains would be considered adulterated.
To perform the testing, test methods needed validation. To conduct method validation, food laboratories required qualitative and quantitative quality controls. Samples to assess the proficiency—or accuracy—of the test providers were also necessary. Yet, culture collections either did not have all the various strains or they did not have the rights to distribute them in time to meet the directive. In fact, it took more than a year from the announcement before the six STEC strains were available in convenient formats, enumerated derivatives, or certified reference materials.
The same concern surfaces in the clinical setting. Emerging microorganisms that create threats to public health require clinical laboratory testing. As demand for diagnoses increases around new strains, laboratories need to have proper test methods, quality controls, and proficiency testing. Culture collections must be able to respond.
More than a year ago, the U.S. Department of Defense, working in concert with the CDC, the Pennsylvania Department of Health, and local health departments, announced the discovery of the first mcr-1 gene found in bacteria in a human in the United States. The mcr-1 gene, which first emerged in China in 2015, makes bacteria resistant to colistin, which is a last-resort antibiotic used to treat patients with certain multi-drug-resistant infections. It has been discovered primarily in E. coli.1 According to the CDC tracking, since the time of its discovery in the U.S., the mcr-1 gene has been found in 16 additional states. Culture collections must be ready to share the isolate for testing, research, and development purposes.
Culture collections and health policy solutions
More than two years ago, the CDC, in collaboration with the Food and Drug Administration, launched an antimicrobial resistance isolate bank (AR Bank). This collection of microbial pathogens has set lofty goals: support development of diagnostic devices and antimicrobial drug products; advance diagnostic tests for the identification and characterization of resistant bacteria; and accelerate research and development of new antibiotics. The value is clear. With this precious resource, the agencies “will support earlier diagnoses and more effective treatment options that can slow antibiotic resistance.”2 Innovative approaches like this one deserve resource support and encouragement.
As federal directives and guidance are developed in response to a public health concern, more communication and advance collaboration with culture collections and the laboratory quality control and proficiency testing communities may assist in preparations. In support of the public health, culture collections should be accessible and responsive to appropriate recipients.
While there are hundreds of culture collections, it is possible that only one will hold a specific, rare strain. It is also possible that more than one will collect the same microorganisms. At times, a collection may refuse to distribute a strain for legal or financial reasons. From a policy perspective, it is important to recognize these constraints when addressing specific pathogens. Federal agencies should refrain from recommending only one source of distribution.
REFERENCES
- McGann P, Snesrud E, Maybank R, et al. 2016. Erratum for McGann et al., Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(8):5107.
- CDC.gov. 2017. Questions and Answers | Antimicrobial Resistance Isolate Bank | Antibiotic/Antimicrobial Resistance | CDC. [ONLINE] https://www.cdc.gov/drugresistance/resistance-bank/faqs.html.
Robin E. Stombler is President of Auburn Health Strategies, LLC, a strategic and business development firm representing health and science organizations.
