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#drug resistance

5 public questions tagged with this topic.

What is the function of ABC transporters?

ATP-binding cassette superfamily includes hundreds of members across all domains of life encoded by 49 human genes divided into ABCA to ABCG subfamilies. Core architecture comprises two transmembrane domains forming substrate path and specificity filter, and two cytosolic nucleotide-binding domains containing Walker A P-loop GXXGXGKS/T for phosphate binding, Walker B hhhhDE coordinating Mg2+ and catalytic glutamate, and signature LSGGQ hallmark. ATP binding drives NBD dimerization sandwiching two ATPs, converting TMDs to outward-facing conformation; hydrolysis and release of ADP and Pi resets inward-facing state enabling vectorial translocation against gradient. In bacteria they primarily serve as high-affinity importers for sugars, amino acids, phosphate, vitamins and siderophores using periplasmic binding proteins. In eukaryotes they act as exporters moving phospholipids, sterols, bile acids, retinoids, heme, xenobiotics, and immunologically TAP1/TAP2 transport peptides for MHC I presentation. CFTR ABCC7 even evolved into chloride channel gated by ATP binding, illustrating diversification of same ATP-switch engine for varied functions.

Ref: Dean et al., Genome Res 2001, Human ABC family; Rees et al., Nat Rev Mol Cell Biol 2009.

Which bacterial enzyme hydrolyzes β-lactam antibiotics, leading to resistance?

Resistance to beta-lactam antibiotics including penicillins, cephalosporins, monobactams and carbapenems frequently arises through enzymatic destruction rather than target alteration. Beta-lactamases are hydrolases classified into Ambler molecular classes A to D based on amino acid sequence homology and catalytic mechanism. Serine beta-lactamases, including plasmid-encoded TEM-1, SHV-1, extended-spectrum beta-lactamases CTX-M and serine carbapenemases KPC, employ an active-site serine residue that performs nucleophilic attack on carbonyl carbon of the strained beta-lactam ring, forming a transient covalent acyl-enzyme intermediate that is rapidly hydrolyzed by activated water molecule, opening the ring irreversibly and rendering drug unable to acylate PBPs. Metallo-beta-lactamases like NDM, VIM and IMP are class B enzymes that use one or two Zn2+ ions to polarize water for direct nucleophilic attack, capable of hydrolyzing almost all beta-lactams except aztreonam. Production can be chromosomally encoded or plasmid-encoded, inducible or constitutive, often associated with porin loss compounding resistance. DNA gyrase is target of fluoroquinolones, catalase detoxifies hydrogen peroxide, transpeptidase is the drug target rather than resistance enzyme, distinguishing beta-lactamase as the specific deactivating enzyme responsible for clinical failure of beta-lactams.

Ref: Prescott's Microbiology, 11th ed., Chapter 36: Beta-Lactamase Enzymes and Antibiotic Resistance.

Drug resistance in bacteria is an example of

Natural selection reflects key principle in quiz on theory of evolution, where evolutionary mechanisms shape genetic variation and adaptation. In this context, Natural selection aligns with experimental and theoretical evidence from population genetics, behavioral ecology and molecular phylogeny. Textbooks like Campbell Biology, Futuyma Evolution and Hartl Principles illustrate supporting data. Understanding why Natural selection fits helps integrate natural selection, environment.

Ref: Campbell Biology, 12th ed., Chapter 22: Descent with Modification.

One mechanism of chemotherapy resistance is

Defective apoptotic machinery, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

MDR1 gene encodes

Over-expression of ATP-binding cassette transporters such as P-glycoprotein (encoded by MDR1) actively effluxes a wide range of hydrophobic drugs from the cytoplasm, reducing their intracellular concentration below the therapeutic threshold. This mechanism is a major cause of multidrug resistance in cancer chemotherapy. Inhibition of these pumps is therefore an active area of pharmacological research aimed at restoring drug sensitivity.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)