1. Possible Substitute for Beta-lactam
Antibiotics Through the Exploration of
and make it inefficient in completing the
Penicillin-binding proteins
disruption of the cell wall synthesis. Altered
Nicolle A. Rosa-Mercado, UPR Cayey PBPs found in bacteria can deform the
bacteria’s shape. PBPs give the antibiotic the
Abstract
ability of preventing the formation of the
Beta-lactam antibiotics are a common bacteria’s cell wall; they are specifically
remedy for most bacterial diseases, but involved in the last stages of peptidoglycan
recently it has been discovered that bacteria synthesis. Peptidoglycan is known to be the
are able to develop a resistance to these major component in the bacteria’s cell wall.
antibiotics through enzymes called beta- These proteins are classified according to
lactamases. Beta-lactam antibiotics work by their molecular weight, for example, PBP1a
inhibiting penicillin-binding proteins (PBPs), has a bigger molecular weight than PBP5.
which are essential for cell wall synthesis, There may be more than one type of
because of a ring called the beta-lactam ring. penicillin-binding proteins found in a bacteria
Beta-lactamases break the ring open and or antibiotic.
inhibit the antibiotic. It is of extreme
Although PBPs may be a major threat to
importance to find a non-beta-lactam
bacteria, the overproduction of PBPs causes
antibiotic that has the same ability of
antibiotic resistance in bacteria; also a
inhibiting penicillin-binding proteins.
formation of PBPs with low affinity for
Introduction penicillin, like PBP5, may create this
resistance. Bacteria can also create resistance
Penicillin-binding proteins are a big group to a beta-lactam antibiotic if they have beta-
of proteins that are characterized by uniting to lactamase or the penicillinase enzyme
beta-lactam antibiotics to reinforce the because it breaks the beta-lactam ring open
antibiotic’s efficiency. Beta-lactam antibiotics making the antibiotic ineffective; this process
are a broad group of antibiotics with a beta- is called the enzymatic hydrolysis of the beta-
lactam nucleus in their molecular structure. lactam ring. The deactivation of some
This binding is possible because these penicillin-binding proteins in bacteria can
proteins have similar chemical structure to lead to its death, meaning that some PBPs are
some components of peptidoglycan. essential for the bacteria’s life. An example of
Penicillin-binding proteins have the ability of bacteria that has a high level of resistance to
making a beta-lactam antibiotic, such as beta-lactam antibiotics is Streptococcus
penicillin, efficient, but an altered PBP, as pneumoniae, which is Gram-positive. This
they are called, can weaken an antibiotic resistance however can be mediated by
making several changes in the molecular

2. structure, and the location of some penicillin- In conclusion, penicillin-binding proteins
binding proteins in the bacteria. Penicillin- can be both an advantage and a disadvantage
binding proteins are essential to all antibiotics for bacteria because, in the absence of an
and are a threat to all bacteria. antibiotic, they complete the bacterial cell
wall, but in the presence of a beta-lactam
Hypothesis and Objectives
antibiotic, they may be used to destroy the
The hypothesis for this investigation would bacteria itself. A non-beta-lactam antibiotic
be that antibiotics that have a similar structure which kills bacteria through the manipulation
to beta-lactams might be used to substitute of PBPs would be extremely beneficial due to
them in bacteria that have developed a the fact that the bacteria would not be able to
resistance to beta-lactams. To do this, the become resistant to it through the use of beta-
antibiotic must be able to bind with a lactamase.
penicillin-binding protein so it can destroy the
References:
bacterial cell wall. The objective of this
proposal is to find a non-beta-lactam •http://www.ncbi.nlm.nih.gov/pmc/articles/
antibiotic so that the bacteria is not able to PMC192226/
create a resistance to it through beta-
•Herzberg O., Moult J. (1987) BActerial
lactamase.
Resistance to Beta-Lactam Antibiotics:
Methodology and Expected Results Crystal Structure of Beta-lactamases from
Staphylococcus aureus PC1 at 2.5A
The methodology would consist of
Resolution. Science/ AAAS Vol.236 no.4802
selecting non-beta-lactam antibiotics that
Pp.694-701
behave similarly to beta-lactams at a
molecular level. The selected antibiotics •Basu J., Chattopadhyay R., Kundu M., and
would be inserted into an Escherichia coli Chakrabarti P. (1992) Purification and partial
colony, a Gram-negative bacteria, and a characterization of a penicillin binding
Streptococcus pneumoniae colony, a Gram- protein from Mycobacterium smegmatis.
positive bacteria, to observe which prove to American Society for Microbiology – Journal
be effective and which do not. Depending on of Bacteriology. Vol. 174, No. 14 pp. 4829–
the previous results, the relation between the 4832
non-beta-lactam antibiotic and the penicillin
binding protein would be studied. The
expected conclusions for this experiment
would be to find a non-beta-lactam antibiotic
that is able to effectively kill bacteria through
penicillin-binding proteins.