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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 z microbiology
Mwelwa Reply
microbiology is all about the scientific study of microorganisms, their life changes, their life span, structural punctuality and their phenomenon.
Ridwan
thanks
micah
Best scope in microbiology
Rahul
wat abut skin
Elyas
whatis scope
Amare
what happened when someone died and what happened to the blood
Franca Reply
nice question
Attari
when you die you have no memory and the blood dry off
Falere
what microorganisms is all about?
Ridwan
And how many does the microorganisms is classified?
Ridwan
How are microbs organized
Saskia
what is endoparasites and exo parasite and their example
OGEDE Reply
Endo : inside the body Exo/ecto : outside or on the body
Paul
examples please
OGEDE
Louse for exo/ecto Helminths (worms) for endo
Paul
what's prokaryotic
mohaiminul Reply
A prokaryotic cell is a cell with no membrane bounds organelles
Paul
what are the main effect of parasite?
yunusa Reply
nutritional group of micro organism
Mana Reply
what are the charateristic bacteria, eukaryotes, and viruses have in commom
Ami Reply
what type of bacteria ismor serious
Amare
D N A ar purno rup ki
Ruba Reply
বাংলায় দেখবো DNA এর পূর্রন্যরুপ কি
Ruba
what's microbiology
micah
micro biology is the study of micro organisms,those being unicellular multicellular or a cellular
aniisha
deoxyribonucleic acid is a long molecule that contains our unique genetic code.
aniisha
Does the parasite/parasitology are under microbiology or not
yunusa
Define bacteria
Kainat
Bacteria are a type of biological cell & they constitute a large domain of prokaryotic microorganisms.
raisa
what kind of microbiology
Mira
hello what is main function of T and B cells
Ishaq Reply
T cells are involved in cell-mediated immunity while B cells are primarily responsible for humoral immunity (relating to antibodies)
Janet
what is hepatitis B
Sunday
it's viral infection that attacks the liver and can cause both acute and chronic diseases. the virus is most commonly transmitted from mother to child during birth and delivery, as well as through contact with blood or other body fluids...
Dejene
What are fundamental experiment of microbiology?
Lucky Reply
study of microscopic organisms, unicellular and multicellular
Falere
what are the characteristics of bacteria, viruses, and eukaryotes
Ami
bacteria-are living organism. contain a peptidoglycan/lipopolysaccharide cell wall. VIRUS-are considered as organic structure which interact with living organism don't have acell wall. they have many differents like bacteria size -large(1000nm) virus size-smaller(20-400nm). bacteria ribosomes presen
Dejene
virus ribosomes absence. bacteria living organism. virus b/n living and non-living things
Dejene
eukaryotic cell has a true membrane bond nucleus and has other membranous organelles that allow for compartmenalization of function
Dejene
This answer is wrong
Jeffrey Reply
who discovered the growth curve
Joy Reply
Example of coccus bacteria
Nweke Reply
staphylococcus aureus
Elton
MRSA any bew information
Satish
pl. read any new information about MRSA
Satish
Any stru tural finding about novel corona virus
Satish
Examples of spiral bacteria
Nweke Reply
Example of Bacillus bacteria
Nweke
pusals
manikanta
another one
Nweke
what is the desifection decontamination or sterilization
Sahra Reply
Is the removal of dangerous substances or germs from an area, objects or person
Florence
It is the removal of any pathogen, including their spores
Paul
removal of all forms of life including endospore
abdulbasid
I think there is a difference between disinfection and sterilization... we should consider those....
Mosimanegape
disinfection deals with removing harmful microbes at the surface level it doesn't destroy or kill spores ( it uses oxidizing agents ,alcohols , phenolic comp ,aldehydes etc) but sterilization deals with total elimination of all forms of lives.(this uses heat, steam, radiation and chemicals)
Onyinye
disinfecting is preventing microorganisms while sterilization is killing of microorganisms completely
Janet
what is the meaning of Papanicolaou smear
John
it's Pap smear A test to check for abnormal cells in the cervix.
Mabel

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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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