Antibiotic resistance is one of the most pressing threats humanity faces. Describe some
ways that it develops biologically and/or as a result of human activity.
Any substance that prevents the growth and multiplication of bacteria or kills them can
be considered an antibiotic. Waksman’s experiment that lead to the discovery of
streptomycin and other antibiotics involved streptomyces strains taken from soil being tested
for the ability to produce small-molecule inhibitors of microbial growth in the lab (Yim et al,
2006). Waksman's original definition of an antibiotic said that it is a chemical compound of
microbiological origin with antibiotic properties. Subsequent definitions built on this by
defining. them as an organism-produced chemical that is harmful to other organisms
(Davies, 2006). According to the Bisht et al (2009), the use of antibiotic medications causes
bacterial alterations.
As shown in appendix A, the prevalence of methicillin-resistant Staphylococcus aureus
increased significantly between 1992 and 2001, with nearly 45% of the blood isolates
showing antibiotic resistance by that year. Due to the increase in antibiotic resistance in
2001, the Department of Health in England improved antibiotic resistance surveillance by
requiring MRSA bacteraemia cases to be reported by all hospitals in England (Johnson,
2015). This change made it much easier to monitor the rate of antibiotic resistance. With
both biological and human causes being contributing factors, it can be assumed with
confidence that that number has only risen since 2001. In this essay, the focus will be on the
biological contributions to antibiotic resistance.
Developments in different bacterial strains have exacerbated antibiotic resistance. This is
illustrated by the production of enzymes, efflux pumps, and genetic mutations, among other
factors.
One way in which antibiotic resistance can be caused is through the presence of several
enzymes that alter the antibiotic so that it can no longer interact with its target in the cell
(Benveniste and Davies, 1973). The chemical reactions of the amino glycoside via N-
acetylation, O-nucleotidilation, and O-phosphorylation is one of the most prevalent and
significant resistance mechanisms; these methods enable bacterial resistance to spread
more widely (Silva, 1996).
Aminoglycosides are commonly used antibiotics that disrupt mRNA and transfer RNA
transport, impair ribosome recycling, and result in messenger RNA decoding abnormalities
(Borovinskaya et al, 2007). They were some of the first antibacterials to be used in clinical
settings, thus bacteria have developed a wide range of enzymes that alter the structure of
these antibiotics, rendering them ineffective (Azucena et al, 1997). Aminoglycoside-6'-N-
1
, acetyltransferase-lb is one instance of an enzyme that modifies the antibiotic. The
aminoglycoside antibiotics are rendered inactive by this enzyme's addition of an acetyl group
from acetyl-CoA to the antibiotic (Ahmed et al, 2020).
A structural explanation for the amino glycoside suppression of ribosome recycling was
provided by Borovinskaya et al (2007) using Escherichia coli; they demonstrate that
ribosome recycling factor (RRF) binding leads RNA helix H69 of the large ribosomal subunit,
which is essential for subunit association, to swing away from the subunit interface in X-ray
crystal structures of the Escherichia coli 70S ribosome.
The emergence of efflux pumps is a secondary mechanism through which biological
changes result in antibiotic resistance. These are transport proteins found in Gram-positive,
Gram-negative, and eukaryotic bacteria that help harmful chemicals, such as the majority of
therapeutic antibiotics, evacuate cells and enter the surrounding environment (Webber and
Piddock, 2003).
Efflux pumps discharge antibiotics from cells, which reduces drug accumulation and raises
minimum inhibitory concentrations (Abdi et al, 2020). Bacteria can mutate in response to the
decrease in intracellular antibiotic concentration, allowing them to ultimately withstand higher
antibiotic concentrations (Blair et al, 2014). The volume of data on bacterial genetics points
to the existence of several efflux mechanisms in bacteria; multiple efflux transporters from
various families, with overlapping substrate spectra, may even be present in a single cell.
(Lin et al, 2015).
While it has been proposed that drug specific efflux systems evolved from efflux
determinants of self protection in antibiotic producing Actinomycetes, chromosomal
multidrug efflux determinants are recognised as having an intended maintenance function
unrelated to drug resistance, at least in Gram-negative bacteria (Poole, 2009); thus, specific
processes within cells may be able to adapt to have various uses depending on the cell
demand, providing another plausible explanation for how antibiotic resistance arises.
An additional way in which bacteria develop antibiotic resistance is through horizontal gene
transfer, arguably an evolutionary inevitability. Bacterial cells obtain genetic material from
antibiotic-resistant bacteria via genetic transfer, making them antibiotic-resistant as well;
antibiotic exposure kills non-resistant bacteria while allowing antibiotic resistance bacteria to
proliferate (Milken Institute School of Public Health, 2017). Some bacterial strains have a
higher propensity to mutate and pass on resistant genes than others, an idea that is
supported through a study conducted by Bjorkholk et al (2001) who discovered that
approximately one-fourth of Helicobacter Pylori isolates had higher mutation frequencies
2
ways that it develops biologically and/or as a result of human activity.
Any substance that prevents the growth and multiplication of bacteria or kills them can
be considered an antibiotic. Waksman’s experiment that lead to the discovery of
streptomycin and other antibiotics involved streptomyces strains taken from soil being tested
for the ability to produce small-molecule inhibitors of microbial growth in the lab (Yim et al,
2006). Waksman's original definition of an antibiotic said that it is a chemical compound of
microbiological origin with antibiotic properties. Subsequent definitions built on this by
defining. them as an organism-produced chemical that is harmful to other organisms
(Davies, 2006). According to the Bisht et al (2009), the use of antibiotic medications causes
bacterial alterations.
As shown in appendix A, the prevalence of methicillin-resistant Staphylococcus aureus
increased significantly between 1992 and 2001, with nearly 45% of the blood isolates
showing antibiotic resistance by that year. Due to the increase in antibiotic resistance in
2001, the Department of Health in England improved antibiotic resistance surveillance by
requiring MRSA bacteraemia cases to be reported by all hospitals in England (Johnson,
2015). This change made it much easier to monitor the rate of antibiotic resistance. With
both biological and human causes being contributing factors, it can be assumed with
confidence that that number has only risen since 2001. In this essay, the focus will be on the
biological contributions to antibiotic resistance.
Developments in different bacterial strains have exacerbated antibiotic resistance. This is
illustrated by the production of enzymes, efflux pumps, and genetic mutations, among other
factors.
One way in which antibiotic resistance can be caused is through the presence of several
enzymes that alter the antibiotic so that it can no longer interact with its target in the cell
(Benveniste and Davies, 1973). The chemical reactions of the amino glycoside via N-
acetylation, O-nucleotidilation, and O-phosphorylation is one of the most prevalent and
significant resistance mechanisms; these methods enable bacterial resistance to spread
more widely (Silva, 1996).
Aminoglycosides are commonly used antibiotics that disrupt mRNA and transfer RNA
transport, impair ribosome recycling, and result in messenger RNA decoding abnormalities
(Borovinskaya et al, 2007). They were some of the first antibacterials to be used in clinical
settings, thus bacteria have developed a wide range of enzymes that alter the structure of
these antibiotics, rendering them ineffective (Azucena et al, 1997). Aminoglycoside-6'-N-
1
, acetyltransferase-lb is one instance of an enzyme that modifies the antibiotic. The
aminoglycoside antibiotics are rendered inactive by this enzyme's addition of an acetyl group
from acetyl-CoA to the antibiotic (Ahmed et al, 2020).
A structural explanation for the amino glycoside suppression of ribosome recycling was
provided by Borovinskaya et al (2007) using Escherichia coli; they demonstrate that
ribosome recycling factor (RRF) binding leads RNA helix H69 of the large ribosomal subunit,
which is essential for subunit association, to swing away from the subunit interface in X-ray
crystal structures of the Escherichia coli 70S ribosome.
The emergence of efflux pumps is a secondary mechanism through which biological
changes result in antibiotic resistance. These are transport proteins found in Gram-positive,
Gram-negative, and eukaryotic bacteria that help harmful chemicals, such as the majority of
therapeutic antibiotics, evacuate cells and enter the surrounding environment (Webber and
Piddock, 2003).
Efflux pumps discharge antibiotics from cells, which reduces drug accumulation and raises
minimum inhibitory concentrations (Abdi et al, 2020). Bacteria can mutate in response to the
decrease in intracellular antibiotic concentration, allowing them to ultimately withstand higher
antibiotic concentrations (Blair et al, 2014). The volume of data on bacterial genetics points
to the existence of several efflux mechanisms in bacteria; multiple efflux transporters from
various families, with overlapping substrate spectra, may even be present in a single cell.
(Lin et al, 2015).
While it has been proposed that drug specific efflux systems evolved from efflux
determinants of self protection in antibiotic producing Actinomycetes, chromosomal
multidrug efflux determinants are recognised as having an intended maintenance function
unrelated to drug resistance, at least in Gram-negative bacteria (Poole, 2009); thus, specific
processes within cells may be able to adapt to have various uses depending on the cell
demand, providing another plausible explanation for how antibiotic resistance arises.
An additional way in which bacteria develop antibiotic resistance is through horizontal gene
transfer, arguably an evolutionary inevitability. Bacterial cells obtain genetic material from
antibiotic-resistant bacteria via genetic transfer, making them antibiotic-resistant as well;
antibiotic exposure kills non-resistant bacteria while allowing antibiotic resistance bacteria to
proliferate (Milken Institute School of Public Health, 2017). Some bacterial strains have a
higher propensity to mutate and pass on resistant genes than others, an idea that is
supported through a study conducted by Bjorkholk et al (2001) who discovered that
approximately one-fourth of Helicobacter Pylori isolates had higher mutation frequencies
2
