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The Growing Problem of Antibiotic Resistance 张驰 王昳楠 Have we conquered bacteria yet? Why the pharmaceutical industry has cut resources devoted to the development of new antibiotics Lack of financial incentives Short lifetime in the marketplace The most effective antibiotics being held back from widespread use Enzymes involved in the synthesis of the bacterial cell wall Penicillin Vancomycin Components of the system by which bacteria duplicate, transcribe, and translate their genetic information Linezolid Daptomycin 3. Enzymes that catalyze metabolic reactions specifically in bacteria. Take sulfa drugs for example Sulfa drugs, are effective antibiotics because they closely resemble the compound p-aminobenzoic acid (PABA) p-aminobenzoic acid Sulfa Function of PABA PABA is an intermediate in the bacterial synthesis of folate(folic acid). However, humans lack the enzymes to convert PABA to folate,and therefore require a dietary supply of folate anyway,so PABA is considered nonessential and is not recognized as a vitamin for humans. Thus, bacterial growth is limited through folate deficiency without effect on human cells. Function of Sulfa drugs Sulfa drugs are structurally similar to PABA, and their antibacterial activity is due to their ability to interfere with the conversion of PABA to folate by the enzyme dihydropteroate synthetase. Why bacteria become resistant to antibiotics? Take Penicillin for example Penicillin is a β-lactam; that is, it contains a fourmembered β-lactam ring (shown in color). Background By the 1940s, researchers had discovered that certain bacteria possess an enzyme calledβlactamase(or penicillinase). During World War II, none of the major diseasecausing bacteria possessed a gene for β-lactamase. Today, the production of β–lactamase by wide variety of infectious cells is the primary cause of penicillin resistance. How did these species acquire the gene? —— not only among the cells of a given species, but also between species Accessions Conjugation Transduction Transformation Conjugation DNA is passed from one bacterial cell to another Transduction a bacterial gene is carried from cell to cell by a virus Transformation a bacterial cell is able to pick up naked DNA from its surrounding medium Other reasons of bacteria’s resistant Not all penicillin-resistant bacteria have acquired aβ–lactamase gene. possess modifications in their cell walls that block entry of the antibiotic selectively export the antibiotic once it has entered the cell possess modified transpeptidases that fail to bind the antibiotic About AIDS high rate of virus production reverse transcriptase lead to high rate of mutation This problem is being combatted by Taking several different drugs targeted at different viral enzymes designing drugs that interact with the most highly conserved portions of each targeted enzyme Antibiotic abuse Antibiotic resistant bacteria is a growing threat and becoming increasingly common. Antibiotic abuse also places the patient at unnecessary risk of adverse effects of antibiotics. Thank you ~