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Transcript
Streptococcus pneumoniae (S. pneumoniae) is one of the most common bacterial respiratory
pathogens worldwide and responsible for a variety of life threatening infectious diseases including
pneumonia, meningitis and septicaemia (1). In the developing world, 25% of all preventable deaths in
children under five years old are attributed to pneumococcal septicaemia, with over 1.2 million infant
deaths per year. The true burden of invasive pneumococcal disease is thought to be highly
underestimated, with only a small portion of presumptive cases confirmed by conventional
techniques.
S. pneumoniae typically resides in the upper respiratory tract of healthy carriers. Although carriage is
often asymptomatic, if S. pneumoniae gains access to other parts of the airway the inflammatory
response results in disease. Children, the elderly, and immunocompromised patients are most at risk to
developing pneumonia (2). Severe cases may result in bacteraemia, which is associated with increased
morbidity and mortality. As with many infectious diseases, early detection can be crucial to patient
outcomes and survival rates.
Laboratory techniques for identifying pneumococcal infections are dependent on traditional
microbiological methods, many of which are laborious and limiting. The time constraints associated
with identifying S. pneumoniae hinder diagnosis, treatment efficacy and ultimately patient outcomes.
The analytical methods currently employed to detect S. pneumoniae suffer from poor sensitivity and
are not always conclusive in identifying species present. Many clinical laboratories identify S.
pneumoniae by microscopic and colony morphology, or by phenotypic traits such as catalase
negativity and α-haemolysis on blood agar. (3) These tests exclude most, but not all viridians species,
and the inadequacies present a major obstacle for accurate diagnosis. This was exemplified by a
recent study highlighting the original misidentification of viridians species in samples isolated from
HIV-seropositive patients. (4)
Conventional culture methods are also employed. However, these are time consuming and can be
compromised by spontaneous autolysis or antibiotic treatment. The detection of pneumococcal
metabolites in urine, blood, breath and sputum samples represents an attractive alternative, being noninvasive. Though again it has a drawback, including positive results weeks after the onset of infection
and inability to conclusively identify S. pneumoniae from viridians species. (5)
Klebsiella pneumoniae (K. pneumoniae) is a well-known source of community-acquired pneumonia
in certain at-risk groups, causing community-acquired urinary tract infections with bacteraemia (7). K.
pneumoniae is also a common cause of nosocomial infections, with the associated risks and costs;
prolonged antibiotic treatments, extended hospital stays, financial burdens on healthcare providers.
Technical difficulty in prompt detection of K. pneumoniae makes it difficult to respond infection, and
treatments are reactionary rather than pre-emptive. The resistance to antibiotics adds a further
complication and swift treatment is paramount. An aptamer for K. pneumoniae has been developed
with dissociation constant (Kd) of 5.377 nM and the developers outline its potential use in a aqueous
environment compatible sensor (8).
Another example involving an aptamer demonstrated a simple and versatile colorimetric biosensor for
specific detection of S. pneumoniae by combining the signal transducer and catalysed DNA hairpin
assembly-based signal amplification. This strategy has been successfully applied to detect S.
pneumoniae as low as 156 CFU ml−1, and shows good specificity against closely related streptococci
and pathogenic bacteria (9). The developed method enables naked eye analysis of S. pneumoniae in
clinical samples and demonstrates excellent assay versatility (Figure 1).
Figure 1:- DNA transducer-triggered signal switch for visual colorimetric bioanalysis (9)
In both the above, aptamers are shown to be reagents capable of detecting S. pneumoniae sensitively
and in a user-friendly way. However, the limited number of examples highlights the need to exploit
the favourable properties of aptamers in point-of-care diagnostics further. Relatively small size, lack
of immunogenicity, rock-solid reproducibility in oligonucleotide production and ease of chemical
modification make aptamers ideal components in diagnostic devices (6). This is reflected by an everincreasing interest for incorporating aptamers into diagnostics, working in conjunction with, or
replacing, traditionally used antibodies.
To learn more about Aptamer Group’s diagnostic arm, please visit Aptadx.
References
1)
2)
3)
4)
5)
6)
7)
http://www.nature.com/nrmicro/journal/v6/n4/full/nrmicro1871.html
https://www.nhlbi.nih.gov/health/health-topics/topics/pnu/atrisk
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902818/
https://www.ncbi.nlm.nih.gov/pubmed/19959577/
http://synapse.koreamed.org/DOIx.php?id=10.3947/ic.2013.45.4.351
http://journals.plos.org/plosone/article/asset?id=10.1371/journal.pone.0153637.PDF
http://new.dhh.louisiana.gov/assets/oph/Center-PHCH/Center-CH/infectiousepi/EpiManual/KlebsiellaManual.pdf
8) https://www.google.ch/patents/US20150141270
9) http://www.nature.com/articles/srep11190