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Correspondence: Reply to Deng et al.

Thomas Iv JC, Kersh EN, Gernert KM, Shafer WM, Brian RH.

J Infect Dis. 2019 Oct 3. pii: jiz505. doi: 10.1093/infdis/jiz505. [Epub ahead of print] No abstract available.


Could Dampening Expression of the Neisseria gonorrhoeae mtrCDE-Encoded Efflux Pump Be a Strategy To Preserve Currently or Resurrect Formerly Used Antibiotics To Treat Gonorrhea?

Chen S, Connolly KL, Rouquette-Loughlin C, D'Andrea A, Jerse AE, Shafer WM.

MBio. 2019 Aug 13;10(4). pii: e01576-19. doi: 10.1128/mBio.01576-19.


Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae.

Beggs GA, Zalucki YM, Brown NG, Rastegari S, Phillips RK, Palzkill T, Shafer WM, Kumaraswami M, Brennan RG.

J Bacteriol. 2019 Sep 20;201(20). pii: e00401-19. doi: 10.1128/JB.00401-19. Print 2019 Oct 15.


Evidence of Recent Genomic Evolution in Gonococcal Strains With Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014-2016.

Thomas JC, Seby S, Abrams AJ, Cartee J, Lucking S, Vidyaprakash E, Schmerer M, Pham CD, Hong J, Torrone E, Cyr SS, Shafer WM, Bernstein K, Kersh EN, Gernert KM; Antimicrobial-Resistant Neisseria gonorrhoeae Working Group .

J Infect Dis. 2019 Jun 19;220(2):294-305. doi: 10.1093/infdis/jiz079.


Mechanistic Basis for Decreased Antimicrobial Susceptibility in a Clinical Isolate of Neisseria gonorrhoeae Possessing a Mosaic-Like mtr Efflux Pump Locus.

Rouquette-Loughlin CE, Reimche JL, Balthazar JT, Dhulipala V, Gernert KM, Kersh EN, Pham CD, Pettus K, Abrams AJ, Trees DL, St Cyr S, Shafer WM.

MBio. 2018 Nov 27;9(6). pii: e02281-18. doi: 10.1128/mBio.02281-18.


Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

Cristillo AD, Bristow CC, Torrone E, Dillon JA, Kirkcaldy RD, Dong H, Grad YH, Nicholas RA, Rice PA, Lawrence K, Oldach D, Shafer WM, Zhou P, Wi TE, Morris SR, Klausner JD.

Sex Transm Dis. 2019 Mar;46(3):e18-e25. doi: 10.1097/OLQ.0000000000000929.


Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting.

Kahler CM, Nawrocki KL, Anandan A, Vrielink A, Shafer WM.

Front Microbiol. 2018 Aug 21;9:1922. doi: 10.3389/fmicb.2018.01922. eCollection 2018. Review.


cis- and trans-Acting Factors Influence Expression of the norM-Encoded Efflux Pump of Neisseria gonorrhoeae and Levels of Gonococcal Susceptibility to Substrate Antimicrobials.

Rouquette-Loughlin CE, Dhulipala V, Reimche JL, Raterman E, Begum AA, Jerse AE, Shafer WM.

Antimicrob Agents Chemother. 2018 Jul 27;62(8). pii: e00821-18. doi: 10.1128/AAC.00821-18. Print 2018 Aug.


Copper Ions and Coordination Complexes as Novel Carbapenem Adjuvants.

Djoko KY, Achard MES, Phan MD, Lo AW, Miraula M, Prombhul S, Hancock SJ, Peters KM, Sidjabat HE, Harris PN, Mitić N, Walsh TR, Anderson GJ, Shafer WM, Paterson DL, Schenk G, McEwan AG, Schembri MA.

Antimicrob Agents Chemother. 2018 Jan 25;62(2). pii: e02280-17. doi: 10.1128/AAC.02280-17. Print 2018 Feb.


Neisseria gonorrhoeae: Drug Resistance, Mouse Models, and Vaccine Development.

Rice PA, Shafer WM, Ram S, Jerse AE.

Annu Rev Microbiol. 2017 Sep 8;71:665-686. doi: 10.1146/annurev-micro-090816-093530. Review.


Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines.

Alirol E, Wi TE, Bala M, Bazzo ML, Chen XS, Deal C, Dillon JR, Kularatne R, Heim J, Hooft van Huijsduijnen R, Hook EW, Lahra MM, Lewis DA, Ndowa F, Shafer WM, Tayler L, Workowski K, Unemo M, Balasegaram M.

PLoS Med. 2017 Jul 26;14(7):e1002366. doi: 10.1371/journal.pmed.1002366. eCollection 2017 Jul.


Control of gdhR Expression in Neisseria gonorrhoeae via Autoregulation and a Master Repressor (MtrR) of a Drug Efflux Pump Operon.

Rouquette-Loughlin CE, Zalucki YM, Dhulipala VL, Balthazar JT, Doyle RG, Nicholas RA, Begum AA, Raterman EL, Jerse AE, Shafer WM.

MBio. 2017 Apr 11;8(2). pii: e00449-17. doi: 10.1128/mBio.00449-17.


Whole-Genome Sequencing of a Large Panel of Contemporary Neisseria gonorrhoeae Clinical Isolates Indicates that a Wild-Type mtrA Gene Is Common: Implications for Inducible Antimicrobial Resistance.

Vidyaprakash E, Abrams AJ, Shafer WM, Trees DL.

Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e00262-17. doi: 10.1128/AAC.00262-17. Print 2017 Apr. No abstract available.


The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions.

Kandler JL, Acevedo RV, Dickinson MK, Cash DR, Shafer WM, Cornelissen CN.

Mol Microbiol. 2016 Oct;102(1):137-51. doi: 10.1111/mmi.13450. Epub 2016 Jul 18.


Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century.

Unemo M, Del Rio C, Shafer WM.

Microbiol Spectr. 2016 Jun;4(3). doi: 10.1128/microbiolspec.EI10-0009-2015. Review.


The MisR Response Regulator Is Necessary for Intrinsic Cationic Antimicrobial Peptide and Aminoglycoside Resistance in Neisseria gonorrhoeae.

Kandler JL, Holley CL, Reimche JL, Dhulipala V, Balthazar JT, Muszyński A, Carlson RW, Shafer WM.

Antimicrob Agents Chemother. 2016 Jul 22;60(8):4690-700. doi: 10.1128/AAC.00823-16. Print 2016 Aug.


Genetic Resistance Determinants, In Vitro Time-Kill Curve Analysis and Pharmacodynamic Functions for the Novel Topoisomerase II Inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae.

Foerster S, Golparian D, Jacobsson S, Hathaway LJ, Low N, Shafer WM, Althaus CL, Unemo M.

Front Microbiol. 2015 Dec 10;6:1377. doi: 10.3389/fmicb.2015.01377. eCollection 2015.


Phosphoethanolamine Modification of Neisseria gonorrhoeae Lipid A Reduces Autophagy Flux in Macrophages.

Zughaier SM, Kandler JL, Balthazar JT, Shafer WM.

PLoS One. 2015 Dec 7;10(12):e0144347. doi: 10.1371/journal.pone.0144347. eCollection 2015.


Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

Djoko KY, Goytia MM, Donnelly PS, Schembri MA, Shafer WM, McEwan AG.

Antimicrob Agents Chemother. 2015 Oct;59(10):6444-53. doi: 10.1128/AAC.01289-15. Epub 2015 Aug 3.


Characterization of a spermine/spermidine transport system reveals a novel DNA sequence duplication in Neisseria gonorrhoeae.

Goytia M, Hawel L 3rd, Dhulipala VL, Joseph SJ, Read TD, Shafer WM.

FEMS Microbiol Lett. 2015 Aug;362(16). pii: fnv125. doi: 10.1093/femsle/fnv125. Epub 2015 Jul 30.


Future treatment of gonorrhea--novel emerging drugs are essential and in progress?

Unemo M, Shafer WM.

Expert Opin Emerg Drugs. 2015 Sep;20(3):357-60. doi: 10.1517/14728214.2015.1039981. Epub 2015 Jul 3. No abstract available.


Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps.

Su CC, Bolla JR, Kumar N, Radhakrishnan A, Long F, Delmar JA, Chou TH, Rajashankar KR, Shafer WM, Yu EW.

Cell Rep. 2015 Apr 7;11(1):61-70. doi: 10.1016/j.celrep.2015.03.003. Epub 2015 Mar 26.


Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance.

Ezewudo MN, Joseph SJ, Castillo-Ramirez S, Dean D, Del Rio C, Didelot X, Dillon JA, Selden RF, Shafer WM, Turingan RS, Unemo M, Read TD.

PeerJ. 2015 Mar 5;3:e806. doi: 10.7717/peerj.806. eCollection 2015.


On the in vivo significance of bacterial resistance to antimicrobial peptides.

Bauer ME, Shafer WM.

Biochim Biophys Acta. 2015 Nov;1848(11 Pt B):3101-11. doi: 10.1016/j.bbamem.2015.02.012. Epub 2015 Feb 18. Review.


Overproduction of the MtrCDE efflux pump in Neisseria gonorrhoeae produces unexpected changes in cellular transcription patterns.

Ohneck EA, Goytia M, Rouquette-Loughlin CE, Joseph SJ, Read TD, Jerse AE, Shafer WM.

Antimicrob Agents Chemother. 2015 Jan;59(1):724-6. doi: 10.1128/AAC.04148-14. Epub 2014 Nov 3.


Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future.

Unemo M, Shafer WM.

Clin Microbiol Rev. 2014 Jul;27(3):587-613. doi: 10.1128/CMR.00010-14. Review.


Crystal structure of the Neisseria gonorrhoeae MtrD inner membrane multidrug efflux pump.

Bolla JR, Su CC, Do SV, Radhakrishnan A, Kumar N, Long F, Chou TH, Delmar JA, Lei HT, Rajashankar KR, Shafer WM, Yu EW.

PLoS One. 2014 Jun 5;9(6):e97903. doi: 10.1371/journal.pone.0097903. eCollection 2014.


Crystal structure of the open state of the Neisseria gonorrhoeae MtrE outer membrane channel.

Lei HT, Chou TH, Su CC, Bolla JR, Kumar N, Radhakrishnan A, Long F, Delmar JA, Do SV, Rajashankar KR, Shafer WM, Yu EW.

PLoS One. 2014 Jun 5;9(6):e97475. doi: 10.1371/journal.pone.0097475. eCollection 2014.


Identification of regulatory elements that control expression of the tbpBA operon in Neisseria gonorrhoeae.

Vélez Acevedo RN, Ronpirin C, Kandler JL, Shafer WM, Cornelissen CN.

J Bacteriol. 2014 Aug;196(15):2762-74. doi: 10.1128/JB.01693-14. Epub 2014 May 16.


Phase-variable expression of lptA modulates the resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides.

Kandler JL, Joseph SJ, Balthazar JT, Dhulipala V, Read TD, Jerse AE, Shafer WM.

Antimicrob Agents Chemother. 2014 Jul;58(7):4230-3. doi: 10.1128/AAC.03108-14. Epub 2014 May 12.


Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae.

Golparian D, Shafer WM, Ohnishi M, Unemo M.

Antimicrob Agents Chemother. 2014 Jun;58(6):3556-9. doi: 10.1128/AAC.00038-14. Epub 2014 Apr 14.


Challenges with gonorrhea in the era of multi-drug and extensively drug resistance - are we on the right track?

Unemo M, Golparian D, Shafer WM.

Expert Rev Anti Infect Ther. 2014 Jun;12(6):653-6. doi: 10.1586/14787210.2014.906902. Epub 2014 Apr 4.


Phosphoethanolamine decoration of Neisseria gonorrhoeae lipid A plays a dual immunostimulatory and protective role during experimental genital tract infection.

Packiam M, Yedery RD, Begum AA, Carlson RW, Ganguly J, Sempowski GD, Ventevogel MS, Shafer WM, Jerse AE.

Infect Immun. 2014 Jun;82(6):2170-9. doi: 10.1128/IAI.01504-14. Epub 2014 Mar 31.


Neisseria gonorrhoeae modulates iron-limiting innate immune defenses in macrophages.

Zughaier SM, Kandler JL, Shafer WM.

PLoS One. 2014 Jan 28;9(1):e87688. doi: 10.1371/journal.pone.0087688. eCollection 2014.


Lipid A's structure mediates Neisseria gonorrhoeae fitness during experimental infection of mice and men.

Hobbs MM, Anderson JE, Balthazar JT, Kandler JL, Carlson RW, Ganguly J, Begum AA, Duncan JA, Lin JT, Sparling PF, Jerse AE, Shafer WM.

MBio. 2013 Nov 19;4(6):e00892-13. doi: 10.1128/mBio.00892-13.


Spermine impairs biofilm formation by Neisseria gonorrhoeae.

Goytia M, Dhulipala VL, Shafer WM.

FEMS Microbiol Lett. 2013 Jun;343(1):64-9. doi: 10.1111/1574-6968.12130. Epub 2013 Apr 4.


Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing.

Lewis LA, Shafer WM, Dutta Ray T, Ram S, Rice PA.

Infect Immun. 2013 Jan;81(1):33-42. doi: 10.1128/IAI.00751-12. Epub 2012 Oct 15.


Impact of fluoroquinolone resistance mutations on gonococcal fitness and in vivo selection for compensatory mutations.

Kunz AN, Begum AA, Wu H, D'Ambrozio JA, Robinson JM, Shafer WM, Bash MC, Jerse AE.

J Infect Dis. 2012 Jun 15;205(12):1821-9. doi: 10.1093/infdis/jis277. Epub 2012 Apr 5.


Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future.

Unemo M, Shafer WM.

Ann N Y Acad Sci. 2011 Aug;1230:E19-28. doi: 10.1111/j.1749-6632.2011.06215.x. Review.


MpeR regulates the mtr efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance by an iron-responsive mechanism.

Mercante AD, Jackson L, Johnson PJ, Stringer VA, Dyer DW, Shafer WM.

Antimicrob Agents Chemother. 2012 Mar;56(3):1491-501. doi: 10.1128/AAC.06112-11. Epub 2012 Jan 3.


The iron-repressed, AraC-like regulator MpeR activates expression of fetA in Neisseria gonorrhoeae.

Hollander A, Mercante AD, Shafer WM, Cornelissen CN.

Infect Immun. 2011 Dec;79(12):4764-76. doi: 10.1128/IAI.05806-11. Epub 2011 Sep 26.


A novel mechanism of high-level, broad-spectrum antibiotic resistance caused by a single base pair change in Neisseria gonorrhoeae.

Ohneck EA, Zalucki YM, Johnson PJ, Dhulipala V, Golparian D, Unemo M, Jerse AE, Shafer WM.

MBio. 2011 Sep 20;2(5). pii: e00187-11. doi: 10.1128/mBio.00187-11. Print 2011.


The evolution of infectious agents in relation to sex in animals and humans: brief discussions of some individual organisms.

Reed DL, Currier RW, Walton SF, Conrad M, Sullivan SA, Carlton JM, Read TD, Severini A, Tyler S, Eberle R, Johnson WE, Silvestri G, Clarke IN, Lagergård T, Lukehart SA, Unemo M, Shafer WM, Beasley RP, Bergström T, Norberg P, Davison AJ, Sharp PM, Hahn BH, Blomberg J.

Ann N Y Acad Sci. 2011 Aug;1230:74-107. doi: 10.1111/j.1749-6632.2011.06133.x. Review.


Lipooligosaccharide Structure is an Important Determinant in the Resistance of Neisseria Gonorrhoeae to Antimicrobial Agents of Innate Host Defense.

Balthazar JT, Gusa A, Martin LE, Choudhury B, Carlson R, Shafer WM.

Front Microbiol. 2011 Feb 18;2:30. doi: 10.3389/fmicb.2011.00030. eCollection 2011.


Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC.

Hobbs MM, Sparling PF, Cohen MS, Shafer WM, Deal CD, Jerse AE.

Front Microbiol. 2011 May 31;2:123. doi: 10.3389/fmicb.2011.00123. eCollection 2011.

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