5.7 Concluding Remarks
181
the alkaline/radon soil was investigated because of its ethnopharmacological use as
a cure for infections. Other hints are very likely to come from, amongst other areas,
extensions to work on how the gut microbiome is modulated (Elgart and Soen 2018),
and the identification of new antibacterial compounds from nature using screening
methods which employ antibiotic resisistance as a possible filtering criterion. This
is seemingly contradictory but it can yield higher hit rates (Thaker et al. 2013).
It will be increasingly important to try and be fundamentally different in future
antibacterial research, and not so much more of the same. This will not be easy
to do. Is it possible to make a quantum leap rather than progressive small jumps
as largely suggested in this book, although some attempts have been made to try
and include some more radical suggestions for research. Quantum leaps, though,
will hinge on new chemistry and new biology using compounds not considered
today and which might engender new interactions with biological targets and be
multiply and selectively active. One will still be limited in a sense by nature since the
targets available will be those in the natural world like proteins, nucleic acids, fatty
acids, or polysaccharides. But perhaps in future therapies these can first be made
‘unnatural’ to allow for radically new interactions with other small molecules? Also
one wonders if new ways of destroying pathogenic bacterial cells from within can be
devised possibly using light-mediated in-cell free radical polymerisation to produce
toxic polymeric assemblages. Recent work has established that light-mediated free
radical polymerisation was possible in HeLa cells using a biocompatible initiator
and various monomers while maintaining cell viability (Geng et al. 2019). With
pathogenic bacteria though the goal would be ultimate non-viability.
In the realisation and translation of any new or radical proposals multidisciplinary
participation and collaboration will continue to be vital including collaborations
between academia, research institutions and pharma (large, medium and small). It is
unfortunate, however, that a number of big pharma have withdrawn from this antibacterial field like Novartis in 2018 (Megget 2018) or are showing declining interest.
Another company Allergan is also divesting antibiotic assets and biotechs are not
doing too well in this space (Shlaes 2018). Clear monetary reward incentives for
antibiotic development are needed and continuing support through WHO, and international Trusts, Funds, Alliances, and Foundations will be increasingly important in
the future (Wanted: a reward for antibiotic development 2018).
Much will always remain to be done and new avenues followed. The challenges
of drug-resistant bacterial infections are great but the likely health benefits for the
global community will hopefully provide the stimulus to never give up in the search
for counter measures.
References
Abdeen S, Salim N, Mammadova N et al. (2016) GroEL/ES inhibitors as potential antibiotics.
Bioorg Med Chem Lett 26(13):3127–3134
181
the alkaline/radon soil was investigated because of its ethnopharmacological use as
a cure for infections. Other hints are very likely to come from, amongst other areas,
extensions to work on how the gut microbiome is modulated (Elgart and Soen 2018),
and the identification of new antibacterial compounds from nature using screening
methods which employ antibiotic resisistance as a possible filtering criterion. This
is seemingly contradictory but it can yield higher hit rates (Thaker et al. 2013).
It will be increasingly important to try and be fundamentally different in future
antibacterial research, and not so much more of the same. This will not be easy
to do. Is it possible to make a quantum leap rather than progressive small jumps
as largely suggested in this book, although some attempts have been made to try
and include some more radical suggestions for research. Quantum leaps, though,
will hinge on new chemistry and new biology using compounds not considered
today and which might engender new interactions with biological targets and be
multiply and selectively active. One will still be limited in a sense by nature since the
targets available will be those in the natural world like proteins, nucleic acids, fatty
acids, or polysaccharides. But perhaps in future therapies these can first be made
‘unnatural’ to allow for radically new interactions with other small molecules? Also
one wonders if new ways of destroying pathogenic bacterial cells from within can be
devised possibly using light-mediated in-cell free radical polymerisation to produce
toxic polymeric assemblages. Recent work has established that light-mediated free
radical polymerisation was possible in HeLa cells using a biocompatible initiator
and various monomers while maintaining cell viability (Geng et al. 2019). With
pathogenic bacteria though the goal would be ultimate non-viability.
In the realisation and translation of any new or radical proposals multidisciplinary
participation and collaboration will continue to be vital including collaborations
between academia, research institutions and pharma (large, medium and small). It is
unfortunate, however, that a number of big pharma have withdrawn from this antibacterial field like Novartis in 2018 (Megget 2018) or are showing declining interest.
Another company Allergan is also divesting antibiotic assets and biotechs are not
doing too well in this space (Shlaes 2018). Clear monetary reward incentives for
antibiotic development are needed and continuing support through WHO, and international Trusts, Funds, Alliances, and Foundations will be increasingly important in
the future (Wanted: a reward for antibiotic development 2018).
Much will always remain to be done and new avenues followed. The challenges
of drug-resistant bacterial infections are great but the likely health benefits for the
global community will hopefully provide the stimulus to never give up in the search
for counter measures.
References
Abdeen S, Salim N, Mammadova N et al. (2016) GroEL/ES inhibitors as potential antibiotics.
Bioorg Med Chem Lett 26(13):3127–3134