Antibiotic Resistance Lab Report

Introduction
Antibiotics are drugs that have been developed to destroy or show interference with the growth of microorganisms. The first antibiotic properties revealed were synthetic chemicals, particularly drugs containing arsenic, which were discovered by Ehrlich at the beginning of the 20th century. Sulphonamide inhibitors of folate metabolism were developed by Domagz in the 1930s which then followed with the development of the first true antibiotic, penicillin in the 1940s.(Wright 2011) Upon this discovery, production and distribution of antibiotic drugs increased and within five years antibiotic resistance was distinguished. Not only do antibiotics help save lives but incorrect use of antibiotics exposes the microbes to the drug where
Multiple mutations may increase the level of resistance while single mutations deliver a high level of resistance. The change in the amino acid sequence modifies the structure of the protein enough to interfere with antibiotic binding and action. Target modification can also occur through highly efficient and region specific modification catalysed by enzymes. An example of this method is ribosome methyltransferase. The ribosomal ribonucleic acid (rRNA) resistance gene, erythromycin-resistant methylase (Erm) transforms the 23S rRNA of the ribosome creating resistance to 3 different classes of antibiotics; macrolides e.g. erythromycin, lincosamides eg. Clindamycin and type B streptogramins e.g. quinupristin. Although these antibiotics differ in molecular structure, they all bind to a specific site on the peptide exit tunnel of the large subunit of the ribosome and block the antibiotic binding site. Another important mechanism is chemical modification, this was first recorded in 1940 with the discovery of penicillin which was found to inactivate β-lactamase activity. β-lactamase enzymes are considered the most important and widespread resistance enzyme. Chemical modifications operate by forming a covalent enzyme intermediate followed by hydrolysis, or metal-activation of a nucleophilic water molecule. (Wright 2011) Gram negative bacteria that produce extended spectrum β-lactamase enzymes (ESBL) have been
The five classes of bacterial efflux systems are the major facilitator (MF) superfamily, the ATP-binding cassette (ABC) family, the resistance-nodulation-division (RND) family, the small multidrug resistance (SMR) family and the multidrug and toxic compound extrusion (MATE) family. RND family transporters are frequently found in Gram-negative bacteria and usually operate as part of a tripartite system that contains a periplasmic membrane fusion protein (MFP) and an outer membrane factor (OMF). This organisation is also seen on occurrence with ABC and MF family exporters. All members but the ABC family function as secondary transporters, catalysing drug-ion antiport. Efflux mediated resistance to biocides exhibit a wide range of substrate specificity. Quaternary ammonium compounds (QAC) have been defined in Gram-positive bacteria majority being in the Staphylococcus spp. Most of the determinants are plasmid-encoded SMR family exporters e.g. QacG, and QacH, although QacA/B is a MF family efflux system, through plasmid acquisition resistance occurs. Chromosomal efflux determinants of QAC resistance although rare in Gram-positive, have been