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Trimethoprim is a synthetic antimicrobial compound that serves as an antimetabolite within the same folic acid synthesis pathway as sulfonamides. However, trimethoprim is a structural analogue of dihydrofolic acid and inhibits a later step in the metabolic pathway ( [link] ). Trimethoprim is used in combination with the sulfa drug sulfamethoxazole to treat urinary tract infection s, ear infection s, and bronchitis . As discussed, the combination of trimethoprim and sulfamethoxazole is an example of antibacterial synergy. When used alone, each antimetabolite only decreases production of folic acid to a level where bacteriostatic inhibition of growth occurs. However, when used in combination, inhibition of both steps in the metabolic pathway decreases folic acid synthesis to a level that is lethal to the bacterial cell. Because of the importance of folic acid during fetal development, sulfa drugs and trimethoprim use should be carefully considered during early pregnancy.

The drug isoniazid is an antimetabolite with specific toxicity for mycobacteria and has long been used in combination with rifampin or streptomycin in the treatment of tuberculosis . It is administered as a prodrug, requiring activation through the action of an intracellular bacterial peroxidase enzyme, forming isoniazid-nicotinamide adenine dinucleotide (NAD) and isoniazid-nicotinamide adenine dinucleotide phosphate (NADP), ultimately preventing the synthesis of mycolic acid, which is essential for mycobacterial cell walls. Possible side effects of isoniazid use include hepatotoxicity , neurotoxicity , and hematologic toxicity ( anemia ).

PABA binds to an enzyme to produce dihydrofolic acid, which binds to another enzyme to produce tetrahydrofolic acid and nucletides. Trimethoprim, a structural analog of dihydrofolic acid, completely inhibits the synthesis of tetrtahydrofolic acid. Sulfonamide, a structural analog of PABA, competitively inhibits the synthesis of dihydrofolic acid.
Sulfonamides and trimethoprim are examples of antimetabolites that interfere in the bacterial synthesis of folic acid by blocking purine and pyrimidine biosynthesis, thus inhibiting bacterial growth.
Antimetabolite Drugs
Metabolic Pathway Target Mechanism of Action Drug Class Specific Drugs Spectrum of Activity
Folic acid synthesis Inhibits the enzyme involved in production of dihydrofolic acid Sulfonamides Sulfamethoxazole Broad spectrum against gram-positive and gram-negative bacteria
Sulfones Dapsone
Inhibits the enzyme involved in the production of tetrahydrofolic acid Not applicable Trimethoprim Broad spectrum against gram-positive and gram-negative bacteria
Mycolic acid synthesis Interferes with the synthesis of mycolic acid Not applicable Isoniazid Narrow spectrum against Mycobacterium spp., including M. tuberculosis
  • How do sulfonamides and trimethoprim selectively target bacteria?

Inhibitor of atp synthase

Bedaquiline, representing the synthetic antibacterial class of compounds called the diarylquinolones , uses a novel mode of action that specifically inhibits mycobacterial growth. Although the specific mechanism has yet to be elucidated, this compound appears to interfere with the function of ATP synthases, perhaps by interfering with the use of the hydrogen ion gradient for ATP synthesis by oxidative phosphorylation , leading to reduced ATP production. Due to its side effects , including hepatotoxicity and potentially lethal heart arrhythmia, its use is reserved for serious, otherwise untreatable cases of tuberculosis .

Part 2

Reading thorough Marisa’s health history, the doctor noticed that during her hospitalization in Vietnam, she was catheterized and received the antimicrobial drugs ceftazidime and metronidazole . Upon learning this, the doctor ordered a CT scan of Marisa’s abdomen to rule out appendicitis; the doctor also requested blood work to see if she had an elevated white blood cell count, and ordered a urine analysis test and urine culture to look for the presence of white blood cells, red blood cells, and bacteria.

Marisa’s urine sample came back positive for the presence of bacteria, indicating a urinary tract infection (UTI). The doctor prescribed ciprofloxacin. In the meantime, her urine was cultured to grow the bacterium for further testing.

  • What types of antimicrobials are typically prescribed for UTIs?
  • Based upon the antimicrobial drugs she was given in Vietnam, which of the antimicrobials for treatment of a UTI would you predict to be ineffective?

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Key concepts and summary

  • Antibacterial compounds exhibit selective toxicity , largely due to differences between prokaryotic and eukaryotic cell structure.
  • Cell wall synthesis inhibitors, including the β-lactams , the glycopeptides , and bacitracin , interfere with peptidoglycan synthesis, making bacterial cells more prone to osmotic lysis.
  • There are a variety of broad-spectrum, bacterial protein synthesis inhibitors that selectively target the prokaryotic 70S ribosome, including those that bind to the 30S subunit ( aminoglycosides and tetracyclines ) and others that bind to the 50S subunit ( macrolides , lincosamides , chloramphenicol , and oxazolidinones ).
  • Polymyxins are lipophilic polypeptide antibiotics that target the lipopolysaccharide component of gram-negative bacteria and ultimately disrupt the integrity of the outer and inner membranes of these bacteria.
  • The nucleic acid synthesis inhibitors rifamycins and fluoroquinolones target bacterial RNA transcription and DNA replication, respectively.
  • Some antibacterial drugs are antimetabolites , acting as competitive inhibitors for bacterial metabolic enzymes. Sulfonamides and trimethoprim are antimetabolites that interfere with bacterial folic acid synthesis. Isoniazid is an antimetabolite that interferes with mycolic acid synthesis in mycobacteria.

Fill in the blank

Selective toxicity antimicrobials are easier to develop against bacteria because they are ________ cells, whereas human cells are eukaryotic.

prokaryotic

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True/false

β-lactamases can degrade vancomycin.

false

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Short answer

If human cells and bacterial cells perform transcription, how are the rifamycins specific for bacterial infections?

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What bacterial structural target would make an antibacterial drug selective for gram-negative bacteria? Provide one example of an antimicrobial compound that targets this structure.

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Questions & Answers

what is the size of virus
Beatrice Reply
What is the difference between TVC and Bioburden test
Mohamed
?
Mohamed
structure of bacteria and 10 types
Jennifer Reply
what is accidental host?
Domingo Reply
what is endomembrane system
Ikpi Reply
what is human anatomy
Ikpi
okay. Go ahead and ask
Blessing Reply
Industrial microbiology mcq
mohamed
Okay. What's your question?
Blessing
life arises from living matter or live organism.
Swami Reply
yes
sildra
I think live matter arises from non living matter
sildra
I dont think so...can u explain with an example
Manya
living maters made by non living matters
sildra
non living matters like stones? rocks?
Manya
eno
sildra
no
sildra
then?
Manya
cells are made by C N O minerals etc
sildra
I mentioned these as non living maters
sildra
that's all
sildra
cells are made up of those things but they originate from living things..
Manya
ok
sildra
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Manya
where are you from
sildra
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sildra
India...u?
Manya
Tamil nadu
sildra
I am from Maharashtra
Manya
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sildra
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Manya
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sildra
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sildra
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Manya
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sildra
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Manya
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sildra
have to give an entrance exam for every college here...so lets c
Manya
food industries, medical lab, vaccine industries ,etc
sildra
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Manya
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Manya
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sildra
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sildra
hello
Udhaya
Hi
Maruf
Family kindly help me with this question? 1) Shortlist the configurative measurements of the following human anatomical ranges of÷ - Blood ( haemeglobin) in both male and female - Haematocytes in both male and female - Hepatocytes in both male and female - Lymphocyte / T. Lymphocytes in both male
Gifted
My names are Gift Mwale and am a Zambian. Kindly help me with this research which goes like this... 1) Shortlist the configurative measurements of the following human anatomical ranges of ÷ - Blood ( haemeglobin) in both male and female - Hepatocytes in both male and female - Haematocytes in both
Gifted
please what is the full meaning for TCDS
UDEME
from a single cell
Freedom
tcds means transcranial direct current stimulation...in this small electric currents are given to brain( specific parts) to help increase brain performance or to help with depression.. current should be in range 0.5-2.0mA
Manya
what's underlying disease relating unsanitary diet microorganism with the highest rate of epidemology solution and efficacy leading molecules elucidated structural solutions
feven
please can anybody talk about brain tumour and its cure.
BELLO Reply
enlargement of the thyroid gland resulting in over production of hormone.
Kamal Reply
What can u say on Thyroid Cancer?
Abdulkareem
Please, talk about the thyroid cancer.
BELLO
explain the Grave's disease
John Reply
what is cell
Avi Reply
is unit of life
Kamaluddeen
Ok
mohamed
who is an industrial microbiologist
Cynthia Reply
I want to know the biochemical composition of bacteria
Josh Reply
It contains peptidoglcon, DNA nd RNA
Asiya
what are Carrier protein
Ikpi
bacteriophage disadvantage
Momina Reply
disease due to __________ abnormalities are termed primary immunodeficiencies
Tayee Reply
Some primary immunodeficiencies are due to a defect of a single cellular or humoral component of the immune system.
Prince
Examples of primary immunodeficiencies include: chronic granulomatous disease, X-linked agammaglobulinemia, selective IgA deficiency etc
Prince
thank you
Nana
explain microbial mutation
Emerald
what is mutation
Cynthia Reply
alteration in genetic makeup
UDEME

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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