Bacterial cells have an extra layer beyond the plasma
membrane known as the cell wall that is composed of peptidoglycans (Williamson,
Collatz, & Gutmann, 1986). This wall provides stability by regulating the
cell's osmolarity (Williamson, Collatz, & Gutmann, 1986). Beta-lactam
antibiotics are a group of antibiotics including Penicillins and Cephalosporins
that attack the cell wall to kill bacteria (Williamson, Collatz, & Gutmann,
1986). The first beta-lactam
antibiotic was discovered in 1928 and since then these antibiotics have
effectively been used to treat a wide variety of diseases (Kong, Schneper,
& Mathee, 2010). However, as society has learned, bacteria are highly adaptable
and have started to become resistant to certain antibiotics (Kong, Schneper,
& Mathee, 2010).
A recent study examining elderly patients with urinary tract
infections was able to show that some bacteria switched from the walled-form to
the L-form, in which bacteria no longer have a cell wall, when in the presence of
beta-lactam
antibiotics (Mickiewicz et al., 2019). While many of the cells died once they lost
their cell wall, some of the cells continued to grow and divide after this occurred
(Mickiewicz et al., 2019). Additionally, these L-form bacteria were eventually
able to regain their cell wall to provide a source of infection (Mickiewicz et
al., 2019).
This research could have many implications in how we treat
infections going forward. This phenomenon might partially explain why diseases
such as urinary tract infections have recurrences (Mickiewicz et al., 2019). If the bacteria lose their cell wall and go
into the L-form, beta-lactam
antibiotics will no longer be able to attack the cell wall and therefore be an
ineffective treatment. Additional antibiotics that attack the inside of the
bacteria might need to be given closely after the beta-lactams to prevent
further incidence of the disease.
Kong, K.-F.,
Schneper, L., & Mathee, K. (2010). Beta-lactam Antibiotics: From Antibiosis
to Resistance and Bacteriology. APMIS : Acta Pathologica, Microbiologica, et
Immunologica Scandinavica, 118(1), 1–36. https://doi.org/10.1111/j.1600-0463.2009.02563.x
Mickiewicz,
K. M., Kawai, Y., Drage, L., Gomes, M. C., Davison, F., Pickard, R., Errington,
J. (2019). Possible role of L-form switching in recurrent urinary tract
infection. Nature Communications, 10(1), 4379. https://doi.org/10.1038/s41467-019-12359-3
Williamson, R., Collatz, E., & Gutmann, L. (1986). Mechanisms
of action of beta-lactam antibiotics and mechanisms of non-enzymatic resistance.
Presse Medicale (Paris, France: 1983), 15(46), 2282–2289.
With the prevalence of antibiotic resistant bacteria, I am curious as to the best way to treat urinary tract infections. As mentioned above, antibiotics are available that attack internal components of bacteria. One such class of drugs, tetracyclines, act by inhibiting tRNA from attaching to the A site in prokaryotic 70s ribosomes (Chopra & Roberts, 2001). Since some bacteria are able to adapt and live without their cell walls, it makes sense to me to use something like a tetracycline since no bacteria can live without being able to synthesize protein. However, I am sure there are other reasons why a tetracycline would not be administered as the first treatment option. I personally will do more research into why peptidoglycan attacking antibiotics would be administered before a tetracycline if the possibility of creating resistant bacteria exists.
ReplyDeleteChopra, I., & Roberts, M. (2001). Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance. Microbiology and Molecular Biology Reviews, 65(2), 232–260. https://doi.org/10.1128/MMBR.65.2.232-260.2001