Antibiotics are used in a wealth of health conditions, from treating infectious diseases like pneumonia, to safeguarding patients against common infections following surgery and organ transplantation.
Antibiotic resistance is fast becoming a reality, however, with a rise in hard-to-treat infections, including drug-resistant gonorrhoea and MRSA.
This problem is not helped by the over-use of antibiotics, and, with limited product approvals, medicine is thought by many to be returning to the dark ages.
To revitalise the stagnant antibiotic pipeline, research in the area has become increasingly creative, investigating everything from antibiotic nanotechnologies to compounds found deep within the ocean all in an attempt to identify novel classes of drugs.
Fighting the resistance
Some researchers are taking a more simple approach and, instead of looking to the future, are examining the forgotten therapies of the past.
A team at the University of Leeds have been trawling through data from the 1970s to identify overlooked compounds that exhibit promising antibiotic characteristics.
Their search led to the re-discovery of pentyl pantothenamide, a previously discarded therapy targeting E-coli.
Using 21st-century techniques, the team of researchers under Dr Michael Webb were able to identify the PanDZ complex as the molecular target for pentyl pantothenamide.
The PanDZ complex is involved in the bacteria-specific synthesis of vitamin B5, which is used as an energy source.
The group is now using this finding to design new drugs targeting the PanDZ complex to attack E-coli in an effective way.
A global effort
Other groups are focusing on synthesising structurally related replacements for widely used antibiotics.
The University of Queensland, in collaboration with Monash University, has been investigating appropriate replacements for the widely used colistin, an effective antibiotic under threat from resistant bacteria.
Through in toto chemical synthesis the team created octapeptin c4, which was later modified to improve specificity to multi-drug-resistant and extensively drug-resistant bacteria.
Preclinical efficacy was later demonstrated in vivo using a murine bacteremia model with a colistin-resistant P. aeruginosa.
These two examples are representative of the global drive within this research area and how the disregarded therapies of the past may yet become the life-saving drugs of tomorrow.
