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Antibiotic resistance in gonorrhea

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to the beta-lactam ring which is a structural characteristic for beta-lactams and hydrolyze the ring. This renders the antibiotic inactive. The spread of the penicillinase resistance was much faster compared to the chromosomal-mediated resistance mechanisms. The plasmids containing TEM-1 could be passed from bacterium to bacterium via conjugation
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component of the bacterial cell wall. PBPs cross-link the amino acid strands of peptidoglycan during synthesis. Normally, beta-lactams bind the PBPs and thereby inhibit the cross-linking of peptidoglycan. When this occurs, the cell wall of the bacterium is compromised and often results in cell death. When
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is mediated by the plasmid borne TEM-1 type beta-lactamase which falls under the third general mechanism for beta-lactam resistance. There have been over 200 beta-lactamases described and some of them are antibiotic specific. TEM-1 is a penicillinase specific for penicillins. This enzyme will bind
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class of antibiotics. These antibiotics bind to the 16s rRNA of the 30S subunit of the bacterial ribosome, thereby inhibiting mRNA translation and protein synthesis. Resistance appears to be acquired through porin-related mechanisms, much like the cephalosporin resistance mechanism. This mechanism
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gene, which encodes for the DNA gyrase, have been seen extensively. DNA gyrase is an enzyme that binds to DNA and introduces negative supercoiling. This helps unwind the DNA for replication. If there is a mutation in the DNA gyrase, then the quinolone will not be able to bind to it resulting in
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gene encodes an alternative penicillin-binding protein, PBP-2. This mechanism falls under the second general mechanism for beta-lactam resistance. PBPs, also known as transpeptidases, are targets for beta-lactams. These enzymes (PBPs) are involved in peptidoglycan synthesis which is a major
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Tetracyclines are a class of antibiotics that inhibit protein synthesis by binding to the 30s ribosomal subunit of bacterial cells, keeping transcription of the bacterial genome from occurring. Tetracyclines are bacteriostatic, which means that the growth of the bacterium will be slowed.
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became available, but by the 1970s resistant strains predominated. Resistance to penicillin has developed through two mechanisms: chromosomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG). CMRNG involves step wise mutation of penA, which codes for the
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Quinolones are a class of synthetic antibiotics that inhibit DNA replication, recombination, and repair by interacting with the bacterial DNA gyrase and/or topoisomerase IV. Second generation quinolones like ciprofloxacin and ofloxacin have been widely used to treat
211:(multiple transferable resistance) gene encodes for an efflux pump. Efflux pumps mediate resistance to a variety of compounds including antibiotics, detergents, and dyes. This mechanism falls under the first general resistance mechanism to beta-lactams. 263:
gene and provides resistance to fluoroquinolones. The NorM efflux pump is a member of the MATE (multidrug and toxic compound extrusion) family and functions by a Na+ antiporter. It is also known that a point mutation upstream of the
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because the treatment regimen requires many doses, which may affect compliance and contribute to resistance. Tetracycline is still used as treatment for this infection in developing countries because the cost for the drug is low
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contains porins which are holes within the cell wall in which some molecules are able to diffuse into or out of the cell membrane. This mechanism falls under the first general mechanism for beta-lactam resistance. The
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Centers for Disease Control Prevention (CDC). (Aug 10, 2012). "Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections".
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would result in the access of the antibiotic to the bacterial cell being inhibited. There is a possibility of future enzymes (made by the bacterium) that will be able to denature and inactivate the aminoglycosides.
219:. MtrD is among the Resistance Nodulation Division (RND) efflux pump superfamily. These pumps are proton antiporters where the antibiotic is pumped out of the cell while a proton is pumped into the cell. 358:(efflux pump formation) mutations mediate chromosomal resistance. These adaptations will also affect the ability of the antibiotic to get into, or stay in the bacterial cell. High level resistance of 79: 271:
High-level resistance to quinolones has been seen through target modification acting on the DNA gyrase and topoisomerase IV. Multiple amino acid substation mutations in the
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have been used to treat gonorrhoea since 2007, but resistant strains have emerged. As of 2010, the recommended treatment is a single 250 mg intramuscular injection of
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Wilson, Brenda A., Abigail A. Salyers, Dixie D. Whitt, and Malcolm A. Winkler. Bacterial Pathogenesis: A Molecular Approach. 3rd ed. Washington DC: ASM Press, 2011. Print.
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gene that encodes for the bacterial porin. This form of resistance has only been observed with ceftriaxone which is administered through an intramuscular injection.
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developing high resistance to penicillin through two main mechanisms: chromosomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG).
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an alteration of more than four amino acids in the C-terminal end of the PBP-2, which would result in the antibiotic being unable to bind to its target
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gene which encodes for the topoisomerase IV. Topoisomerase IV acts similarly to DNA gyrase and is involved in unwinding DNA for replication.
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Low-level quinolone resistance has been linked to changes in cell permeability and efflux pumps. The NorM efflux pump is encoded by the
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and when this gene undergoes mutations, there is a decrease in permeability of the cell wall to hydrophilic antibiotics like penicillin.
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Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. Medical Microbiology. 6th ed. Philadelphia: Mosby/Elsevier, 2009. Print
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infections. Resistance to these antibiotics has developed over the years with chromosomal resistance being the primary mechanism.
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were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes
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Drlica, Zhao (1997) DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiology and Molecular Biology Reviews 61:377–392
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Mosaic Allele in a Successful International Clone Causes Treatment Failure. Antimicrobial Agents and Chemotherapy 1273–1280
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in the 1940s. There are three general mechanisms that may allow bacteria to become resistant to beta-lactam antibiotics:
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Chromosomally mediated resistance occurred through step-wise changes over many years. Chromosomal mutations in the
307:. The cephalosporins are part of a larger beta-lactam family of antibiotics. The newly discovered H041 strain of 204:, the new PBP-2 that is synthesized is no longer recognized by the beta-lactams rendering the bacterium resistant. 915: 884: 851: 846: 73: 38: 76:, and as a result, the existence of any strain resistant to a given drug could spread easily across strains. 734:
Unemo, Golparian, Nicholas, Ohnishi, Gallay, Sednaoui (2011) High-Level Cefixime- and Ceftriaxone-Resistant
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Cases of Neisseria Gonorrhoeae with decreased susceptibility or resistance to antibiotics (2017-2018).
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Deguchi T, Nakane K, Yasuda M, Maeda S (September 2010). "Emergence and spread of drug resistant
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Basic structures of penicillins(1) and cephalosporins(2) with beta-lactam ring highlighted in red
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the activity of DNA gyrase not being inhibited. Multiple mutations have also been noted in the
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Van Bambeke, Balzi, Tulkens (2000) Antibiotic Efflux Pumps. Biochemical Pharmacology 60:457–470
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mosaic alleles and prediction of reduced susceptibility to expanded-spectrum cephalosorins in
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Ligon BL (2005). "Albert Ludwig Sigesmund Neisser: discoverer of the cause of gonorrhea".
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that removes penicillin from the cell; and penB, which encodes the bacterial cell wall
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Rouquette-Loughlin, Dunham, Kuhn, Balthazar, Shafer (2003) The NorM Efflux Pump of
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can be resistant to antibiotics that are normally used to treat it. These include:
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Recognizes Antimicrobial Cationic Compounds. Journal of Bacteriology 185:1101–1106
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gene will causes overexpression of NorM, and mediate elevated resistance.
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Unemo (2008) Real-time PCR and subsequent pyrosequencing for screeing of
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The possible mechanisms of resistance to this antibiotic are as follows:
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are third generation cephalosporins and are often used as treatments for
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to tetracyclines was first reported in 1986 with the discovering of the
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inability to access/target penicillin-binding protein (PBP) enzyme
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to many antibiotics. The bacteria was first identified in 1879.
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Tetracyclines are not often recommended for the treatment of
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hydrolysis/inactivation of the antibiotic by beta-lactamases.
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determinant. The mechanism of resistance is still unknown.
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inhibition of binding to PBP via modification of the enzyme
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encodes for the protein MtrD which is the efflux pump for
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Beta-lactams like penicillin were widely used to treat
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PPNG involves the acquisition of a 7: 14: 377:has also shown resistance to the 102:, sometimes in combination with 603:Pleininge, Sonja (April 2022). 126:(an injectable cephalosporin), 53:(PBP-2); mtr, which encodes an 906:Antimicrobial pharmacodynamics 110:. However, certain strains of 1: 973:Antibiotic-resistant bacteria 493:. World Health Organization. 487:"Antimicrobial resistance in 231:gene encodes the porins for 932:Antibiotic use in livestock 989: 530:10.1016/j.juro.2010.04.078 433:10.1053/j.spid.2005.07.001 51:penicillin-binding protein 916:Production of antibiotics 885:Antimicrobial stewardship 305:N. gonorrhoeae infections 847:Antimicrobial resistance 421:Semin Pediatr Infect Dis 74:horizontal gene transfer 72:has a high affinity for 524:(3): 851–8, quiz 1235. 859:Antibiotic prophylaxis 842:Antibiotic sensitivity 485:Tapsall, John (2001). 354:(porin formation) and 293: 151: 84: 25: 757:Neisseria gonorrhoeae 736:Neisseria gonorrhoeae 688:Neissera meningitidis 684:Neisseria gonorrhoeae 514:Neisseria gonorrhoeae 489:Neisseria gonorrhoeae 400:Antibiotic resistance 393:Neisseria gonorrhoeae 291: 174:Neisseria gonorrhoeae 149: 82: 39:antibiotic resistance 30:Neisseria gonorrhoeae 22:Neisseria gonorrhoeae 19: 947:Pesticide resistance 911:List of antibiotics 94:. Third-generation 294: 152: 85: 26: 955: 954: 890:Antibiotic misuse 738:in France: Novel 609:Euro Surveillance 328:mutations in the 222:The cell wall of 980: 869:Directed therapy 789: 782: 775: 766: 760: 749: 743: 732: 726: 723: 712: 709: 700: 697: 691: 680: 669: 666: 651: 650: 632: 600: 594: 593: 591: 590: 576: 570: 569: 548: 542: 541: 509: 503: 502: 482: 445: 444: 416: 88:Fluoroquinolones 37:, has developed 988: 987: 983: 982: 981: 979: 978: 977: 958: 957: 956: 951: 920: 894: 873: 864:Empiric therapy 830: 799: 793: 763: 750: 746: 733: 729: 724: 715: 710: 703: 698: 694: 681: 672: 667: 654: 602: 601: 597: 588: 586: 578: 577: 573: 550: 549: 545: 511: 510: 506: 484: 483: 448: 418: 417: 413: 409: 388: 372: 370:Aminoglycosides 339: 286: 249: 144: 132:aminoglycosides 12: 11: 5: 986: 984: 976: 975: 970: 960: 959: 953: 952: 950: 949: 944: 939: 934: 928: 926: 922: 921: 919: 918: 913: 908: 902: 900: 896: 895: 893: 892: 887: 881: 879: 875: 874: 872: 871: 866: 861: 856: 855: 854: 844: 838: 836: 832: 831: 829: 828: 823: 818: 813: 807: 805: 801: 800: 797:antimicrobials 794: 792: 791: 784: 777: 769: 762: 761: 744: 727: 713: 701: 692: 670: 652: 595: 571: 543: 504: 446: 410: 408: 405: 404: 403: 396: 387: 384: 379:aminoglycoside 375:N. gonorrhoeae 371: 368: 360:N. gonorrhoeae 344:N. gonorrhoeae 338: 335: 334: 333: 326: 319: 309:N. gonorrhoeae 285: 284:Cephalosporins 282: 254:N. gonorrhoeae 248: 245: 240:N. gonorrhoeae 233:N. gonorrhoeae 224:N. gonorrhoeae 217:N. gonorrhoeae 198:N. gonorrhoeae 170: 169: 166: 163: 143: 140: 112:N. gonorrhoeae 96:cephalosporins 70:N. gonorrhoeae 66:beta-lactamase 20:Gram stain of 13: 10: 9: 6: 4: 3: 2: 985: 974: 971: 969: 966: 965: 963: 948: 945: 943: 940: 938: 935: 933: 930: 929: 927: 923: 917: 914: 912: 909: 907: 904: 903: 901: 897: 891: 888: 886: 883: 882: 880: 878:Social issues 876: 870: 867: 865: 862: 860: 857: 853: 850: 849: 848: 845: 843: 840: 839: 837: 833: 827: 826:Antiparasitic 824: 822: 819: 817: 814: 812: 811:Antibacterial 809: 808: 806: 802: 798: 790: 785: 783: 778: 776: 771: 770: 767: 758: 754: 748: 745: 741: 737: 731: 728: 722: 720: 718: 714: 708: 706: 702: 696: 693: 689: 685: 679: 677: 675: 671: 665: 663: 661: 659: 657: 653: 648: 644: 640: 636: 631: 626: 622: 618: 614: 610: 606: 599: 596: 585: 581: 575: 572: 567: 563: 560:(31): 590–4. 559: 555: 547: 544: 539: 535: 531: 527: 523: 519: 515: 508: 505: 500: 496: 492: 490: 481: 479: 477: 475: 473: 471: 469: 467: 465: 463: 461: 459: 457: 455: 453: 451: 447: 442: 438: 434: 430: 427:(4): 336–41. 426: 422: 415: 412: 406: 402: 401: 397: 395: 394: 390: 389: 385: 383: 380: 376: 369: 367: 365: 361: 357: 353: 348: 345: 337:Tetracyclines 336: 331: 327: 324: 320: 317: 316: 315: 312: 310: 306: 302: 298: 290: 283: 281: 279: 274: 269: 267: 262: 257: 255: 246: 244: 241: 236: 234: 230: 225: 220: 218: 214: 210: 205: 203: 199: 194: 190: 186: 182: 177: 175: 167: 164: 161: 160: 159: 157: 148: 141: 139: 137: 133: 129: 125: 121: 120:cephalosporin 117: 113: 109: 105: 101: 97: 93: 89: 81: 77: 75: 71: 67: 64: 63:plasmid-borne 60: 56: 52: 47: 42: 40: 36: 32: 31: 23: 18: 899:Pharmacology 756: 752: 747: 739: 735: 730: 695: 687: 683: 612: 608: 598: 587:. 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Index


Neisseria gonorrhoeae
gonorrhea
antibiotic resistance
penicillin
penicillin-binding protein
efflux pump
porins
plasmid-borne
beta-lactamase
horizontal gene transfer

Fluoroquinolones
DNA gyrase
cephalosporins
ceftriaxone
azithromycin
doxycycline
cefixime
cephalosporin
ceftriaxone
azithromycin
aminoglycosides
tetracycline

gonorrhea

Ceftriaxone
cefixime
aminoglycoside

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