16
1 Antibacterials
Care 2018). Also resistance to the last-resort antibiotic ceftriaxone (Vincent et al.
2018) has been reported in which the bacterium can maintain a good growth rate
via ‘compensatory’ mutations to counter the growth-slowing effect of the resistance
mutations. This is a real concern and highlights again the need for new antibacterials
for this bacterium.
1.6 Bacterial Over Host Selectivity
Selective toxicity for bacterial cells over host mammalian cells in vivo is a key issue
for both combination and single molecule approaches with the antibacterials being
launched into a sea of other small molecules, together with many macromolecules
both soluble and membrane bound. Important factors include the mode of administration followed by the selective targeting of bacterial cells (intracellular) or contiguous
areas (extra-cellular), as well as considering interactions with bacterially specific
targets for the mediation of the antibacterial activity. Intracellular targeting can be
achieved by passive targeting and passive uptake, passive targeting and selective
uptake (compared with host cells), or by intentional or deliberate targeting and then
uptake. Following this the molecule may then be released with intact antibacterial
activity (Single molecule non-cleavable multiply active antibacterials; Chap. 3) or
be transformed or cleaved (Prodrugs for multiply active antibacterials; Chap. 4).
Similar considerations apply with extra-cellular agents and combinations (Chap. 2)
with either or both intra- and extra-cellular modalities. In Chap. 5 future perspectives
are considered to conclude the book.
References
Almeida A, Mitchell AL, Boland M et al. (2019) A new genomic blueprint of the human gut
microbiota. Nature 568 (7753):499–504
An Q, Li C, Chen Y et al. (2020) Repurposed drug candidates for antituberculosis therapy. Eur J
Med Chem 192: Article 112175
Australian Commission on Safety and Quality in Health Care (2018) Antibiotic resistant gonorrhoea
drives bulk of rise in alerts. https://www.safetyandquality.gov.au/media_releases/antibiotic-resist
ant-gonorrhoea-drives-bulk-of-rise-in-alerts. Accessed 29 Nov 2020
Bansal Y, Silakari O (2014) Multifunctional compounds: smart molecules for multifactorial
diseases. Eur J Med Chem 76:31–42
Blair JMA (2018) A climate for antibiotic resistance. Nature Clim Change 8:458–461
Blair JMA, Webber MA, Baylay AJ et al. (2015) Molecular mechanisms of antibiotic resistance.
Nat Rev Microbiol 13:42–51
Blaskovich M (2016) Keeping up with the microbes. Chem Aust April:16–19
Bolourian A, Mojtahedi Z (2018) Streptomyces, shared microbiome member of soil and gut, as “old
friends” against colon cancer. FEMS Microbiol Ecol 94(8): fiy120, doi:https://doi.org/10.1093/
femsec/fiy120
Bolognesi M L (2013) Polypharmacology in a single drug: Multitarget drugs. Curr Med Chem 20:
1639–1645.
1 Antibacterials
Care 2018). Also resistance to the last-resort antibiotic ceftriaxone (Vincent et al.
2018) has been reported in which the bacterium can maintain a good growth rate
via ‘compensatory’ mutations to counter the growth-slowing effect of the resistance
mutations. This is a real concern and highlights again the need for new antibacterials
for this bacterium.
1.6 Bacterial Over Host Selectivity
Selective toxicity for bacterial cells over host mammalian cells in vivo is a key issue
for both combination and single molecule approaches with the antibacterials being
launched into a sea of other small molecules, together with many macromolecules
both soluble and membrane bound. Important factors include the mode of administration followed by the selective targeting of bacterial cells (intracellular) or contiguous
areas (extra-cellular), as well as considering interactions with bacterially specific
targets for the mediation of the antibacterial activity. Intracellular targeting can be
achieved by passive targeting and passive uptake, passive targeting and selective
uptake (compared with host cells), or by intentional or deliberate targeting and then
uptake. Following this the molecule may then be released with intact antibacterial
activity (Single molecule non-cleavable multiply active antibacterials; Chap. 3) or
be transformed or cleaved (Prodrugs for multiply active antibacterials; Chap. 4).
Similar considerations apply with extra-cellular agents and combinations (Chap. 2)
with either or both intra- and extra-cellular modalities. In Chap. 5 future perspectives
are considered to conclude the book.
References
Almeida A, Mitchell AL, Boland M et al. (2019) A new genomic blueprint of the human gut
microbiota. Nature 568 (7753):499–504
An Q, Li C, Chen Y et al. (2020) Repurposed drug candidates for antituberculosis therapy. Eur J
Med Chem 192: Article 112175
Australian Commission on Safety and Quality in Health Care (2018) Antibiotic resistant gonorrhoea
drives bulk of rise in alerts. https://www.safetyandquality.gov.au/media_releases/antibiotic-resist
ant-gonorrhoea-drives-bulk-of-rise-in-alerts. Accessed 29 Nov 2020
Bansal Y, Silakari O (2014) Multifunctional compounds: smart molecules for multifactorial
diseases. Eur J Med Chem 76:31–42
Blair JMA (2018) A climate for antibiotic resistance. Nature Clim Change 8:458–461
Blair JMA, Webber MA, Baylay AJ et al. (2015) Molecular mechanisms of antibiotic resistance.
Nat Rev Microbiol 13:42–51
Blaskovich M (2016) Keeping up with the microbes. Chem Aust April:16–19
Bolourian A, Mojtahedi Z (2018) Streptomyces, shared microbiome member of soil and gut, as “old
friends” against colon cancer. FEMS Microbiol Ecol 94(8): fiy120, doi:https://doi.org/10.1093/
femsec/fiy120
Bolognesi M L (2013) Polypharmacology in a single drug: Multitarget drugs. Curr Med Chem 20:
1639–1645.