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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

write the life cycle of HIV
Firomsa Reply
describe the internal and external structure of prokaryotic cell in terms of there appearance and functions
Lenia Reply
compare and contrast similar structures found in prokaryotic and eukaryotic cells
Lenia
control of microorganisms
ISTEFAZUL Reply
how can a doctor treat a person affected by endospore forming bacteria in his/her wound?
Mambo Reply
a 28 years old woman come to your clinic with complain of fever painful genital blisters which express clear fluid when ruptured burning sensation around the bristers what is the diagnosis?
Ramadhani Reply
genital herpes caused by a virus called herpe simplex virus
Doris
what is the reference between selective medium and differential medium?
Tony Reply
the micro flora of air is transient why
Princess
Hello.... Am new here
essien Reply
welcome essien
Muhammad
welcome essien
Beka
classification of gram positive
lissa Reply
classify gram positive
lissa
catalase test is done to differentiate between staph and strep. as staph is catalase positive while strep is catalase negative then staph is differentiate further on coagulase positive and coagulase negative. staph aureus is coagulase positive while staph epidermidis is coagulase negative.
Muhammad
gram positive staph is further differentiated on sensitivity test and manitol salt fermentation test while gram positive strep is differentiated on hemolysis pattern
Muhammad
more about gramm positive
lissa
please
lissa
ok
Blessing
am back any gist
Blessing
taxonomy
Rahul
can i use the graph of bacterial growth for my master's thesis?
Christoph Reply
facultative anaerobic bavteria gives uniform turdibity in nutrient broth why?
Princess Reply
oils and waxes are not sterilized in autoclave
Princess
what is the function of paraffin
Muhammad
@ MAHI because they can grow all over the media from surface to the bottom as they can utilize oxygen or conduct fermentation in its absence.
Online
2.@MAHI Autoclave uses steam under pressure. The steam cannot penetrate through oil and wax. Thus, dry heat sterilization is preferred than autoclave .
Online
thnku
Nadiya
how nutirent agar can converted into blood agar
Princess
thank you
Princess
take a nutrient agar ........and add 5ml blood and put in it ...........!
Nadiya
nutrient agar +blood 5ml+ distilled water =blood agar .
Nadiya
mixed wellllll
Nadiya
hi
Rahul
why agar is not a neutrient source?
Shimul
because it's a general purpose agar only use for growing bacteria
Richa
way is antigen
opaleye
what is antigen
opaleye
antigen is a foreign body that cause activation of antibody?
ASNAKE
Antigen is a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies.
Shimul
thanks for that
opaleye
what is pharmacology
Luyenu
a science that studies about the drug
ASNAKE
hello ever one
Sayid
y
Abdul
Work hard
Anigor
y
Abdul
thanks alot
Luyenu
What is the major different between gram positive and gram negative bacteria.
Asikur
bacteria kya hai
Mala
content of their cell wall
Doris
koi mujhse basic microbiology ki study k Lea book suggest kro .
Richa
Harley prescott
Vikas
what are the five predisposing factors of opportunistic infections
Asher Reply
1. long term exposure to diseases, that the body immunity weakens.
prosper
2. Nature Of some diseases to weaken body immunity such as, AIDS.
prosper
3. Use of immuno-suppresive drugs.
prosper
anyone... need a hand here 🙋😞
prosper
Low immune is the major cause eg for kaposis sarcoma
Davismith
suitable conditions e.g temp,
Muhammad
what os gnormal flora
kifayat Reply
morphological and genetic classification of bacteria
Potter Reply
what is the morphogical
Bupe
h
Sudhir
morphologycal is defined as relating to the branch of biology that deals with the form of living organisms,and with relationship between their structures.
Nadiya
relating to the form or structure of things .
Nadiya
what is the meaning of lessions
oluwa
i am frim Afghanistan.
wahidullah Reply
iam from iraq
Haidar
and i'm from pakistan
Muhammad
Nice
Amina
what's about the qualification
Muhammad
Hlo
Asiya
Hmm
Number
Almustafa Muhammad from Nigeria
Mujtafa
am ustaz Abdulsalam from Ghana
ustaz
am Bupe Chifita from Zambia
Bupe
what is microbiology
Bupe
is the study of invisible micro organism
Mujtafa
microbiology is the study of very too small organisms which we can't see with naked eyes ......in other words ....study of microorganism is called microbiology.
Nadiya
Hello! How Can Microorganisms Be Isolated From The Skin?.. 5 ways if possible. (briefly)
prosper
from skin swabbing is the prefer method worldwide
Muhammad
thanks Muhammad Nauman very much!
prosper
hi
Meek
hi Meek
prosper
are there any other ways pals?
prosper
hi prosper
Meek
hello Meek Mild.
prosper
Any question or ideas, Meek?😊
prosper
and if a patient have any blister or abscess on the skin then first cut the blister or abscess. inside material is taking by syringe.
Muhammad
in case of fingernail or toenails simply cut a small piece of nail and culture on the appropriate media at a required temperature and time
Muhammad
Again, thanks Mr. Muhammad! I appreciate the help.
prosper
you welcom prosper 😊
Muhammad
what are the media use for skin swab?
Sieh-Mlanwin
blood and macckonkey mostly usededia for skin bacteria
Muhammad
used media*
Muhammad
@ SIEH mostly fungal infection occurs in skin so SDA ( Sabouraud Dextrose Agar) or MEA ( Malt extract agar) are common.
Online
thanks
Sieh-Mlanwin
Microbiologicam source of vitamins
Bachi Reply
what do you mean?
Md
that's example?
Md
hi everyone
Muhammad
such as. c/s media
Md
hmm hlw
Md
just tell me about that ?
Md
where are u from
Muhammad

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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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