Someone told me avoid describing NAP-1/027 as a single strain.There are multiple strains within this type, and although there is a strong degree of clonality, they should not be discussed as a single strain.
Is that true?
Dear Shu Fang Kuo
BI/NAP1/027strain is a toxin variant strain of C difficile which can cause considerably higher burden of disease and mortality than other strains of C difficile because of five major differences with the rest of the C. difficile strains i.e.
1. In addition to producing toxin A and toxin B producer, it produces a third toxin called binary toxin.
2. The second major difference is that the organism contains a cluster of genes that control toxin production called the pathogenicity locus, or PaLoc. The PaLoc contains 5five individual genes: the genes for toxin A, the genes for toxin B, a gene called tcdR, an alternate sigma factor that promotes production of the toxins, tcdE, a holin or protein that allows toxins to escape the cells, and tcdC, a putative negative regulator of toxin production that down-regulates toxin production. It is worth noting that in these strains, this gene is dysfunctional, and the high toxin production by these strains is thought to be due to the dysfunctional tcdC gene.
3. The third difference is that the BI/NAP1/027 strain has evolved to acquire a high level resistance to fluoroquinolone antibiotics, which include ofloxacin, ciprofloxacin, levofloxacin and moxifloxacin. This high level resistance can also contribute to the dissemination of the organism because these drugs are commonly used in healthcare settings for the treatment of UTI and LRTI. Consequently, if the organism is resistant to the drug that a patient is taking and the patient ingests C difficile spores, the patient can become infected even in the presence of the drug.
4. The fourth difference is that it has been shown that in vitro studies these strains adhere very efficiently to colonic mucosal cells, and this may be a factor that allows them to infect new patients more readily with potentially high infectivity.
5. The fifth difference is that they produce a high proportion of spores when they are under stressful conditions in the environment or in the host. If an organism is able to produce a lot of spores that may be the way C difficile spreads because patients with diarrhoea typically shed C difficile spores into the environment which survive and subsequently leads to the spread of infection to other patients.
With this in mind, it is possible to surmise that the BI/NAP1/027strain of C difficile may produce genomic variants leading to the production of distinct sub-types. However, until such time as these sub-types are fully elucidated with regards to their epidemiology, pathogenicity and antimicrobial susceptibilities, it would be prudent to consider that all of them have a hyper-toxigenic and high infectivity potential which enables them to cause a considerably higher burden of morbidity and mortality in a healthcare setting.
Having said that, I would like to point out that there are major benefits of molecular subtyping of these isolates especially in an outbreak situation. Further molecular subtyping of the BI/NAP1/027 isolates can assist in finding as to whether the patients involved in a cluster are linked to the index case and to each other or are of diverse origin. This can have implication for outbreak control measures and patient management.
Best regards
Sayed
Dr Sayed S Bukhari MD, FRCPath
Consultant in Infection
University Hospitals of Leicester NHS Trust
East Midlands
UK
BI/NAP1/027 refers to different typing systems. These are intended for monitoring/surveillance, but do not reflect strain level discriminatory power (talking evolution). Whole genome sequencing (e.g. He et al Nature Genetics) clearly shows that strains classified in this way are definitely NOT clonal. Also there is great variation in virulence characteristics between differnt BI/NAP1/027 strains with respect to sporulation, toxin production etc (many published studies). So, though it is true that as a whole these strains are more virulent/problematic than certain other types it remains a clinical tool, these qualifications.
Thanks for Dr Sayed S Bukhar ,The answer is so detailed.I learn a lot for
NAP1
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