{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T13:44:25Z","timestamp":1774791865500,"version":"3.50.1"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p><jats:italic>Neisseria gonorrhoeae<\/jats:italic> (gonococcus) infection is one of the most commonly reported nationally notifiable conditions in the United States. Gonococcus has developed antimicrobial resistance to each previously used antibiotic for gonorrhea therapy. However, some isolates may be still susceptible to no longer recommended, yet still effective antibiotics. This in turn suggests that targeted therapy could slow resistance development to currently recommended empirical treatments. We curated a gonococcal Ciprofloxacin Antibiotic Resistance Isolate Bank panel (Cipro-panel) as a tool for validating or developing new tests to determine ciprofloxacin susceptibility.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>The Cipro-panel was selected using whole genome sequencing, bioinformatic tools, and antimicrobial susceptibility testing (AST) data. Isolates were further selected based on nucleotide variations in <jats:italic>gyrA<\/jats:italic> and <jats:italic>parC<\/jats:italic> genes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We selected 14 unique <jats:italic>N<\/jats:italic>. <jats:italic>gonorrhoeae<\/jats:italic> isolates from the 2006\u20132012 Gonococcal Isolate Surveillance Project (GISP) collection. They represented a wide range of antimicrobial susceptibility to ciprofloxacin and commonly observed nucleotide variations of <jats:italic>gyrA<\/jats:italic> and <jats:italic>parC<\/jats:italic> genes. This Cipro-panel consists of 5 isolates with resistant phenotypes (MIC &gt; = 1 \u03bcg\/mL), 8 isolates with susceptible phenotypes (MIC &lt; = 0.06 \u03bcg\/mL), and 1 isolate falling in the Clinical and Laboratory Standards Institute defined intermediate range. Among the <jats:italic>gyrA<\/jats:italic> variations we observed a total of 18 SNPs. Four positions had nonsynonymous changes (nucleotide positions 272, 284, 1093, and 1783). The first two positions (272 and 284) have been linked previously with resistance to ciprofloxacin (i.e. amino acid positions 91 and 95). For the <jats:italic>parC<\/jats:italic> gene, we observed a total of 21 possible SNPs. Eight of those SNPs resulted in non-synonymous amino acid changes. One location (amino acid 87) has been previously reported to be associated with ciprofloxacin resistance.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This Cipro-Panel is useful for researchers interested in developing clinical tests related to ciprofloxacin. It could also provide additional choices for validation, quality assurance purposes and improve antibiotic usage.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0264149","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T18:29:21Z","timestamp":1646936961000},"page":"e0264149","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of a Neisseria gonorrhoeae Ciprofloxacin panel for an antimicrobial resistant Isolate Bank"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4270-3017","authenticated-orcid":true,"given":"Hsi","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cau D.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-1756","authenticated-orcid":true,"given":"Matthew","family":"Schmerer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen N.","family":"Kersh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian H.","family":"Raphael","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"pone.0264149.ref001","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"J Rowley","year":"2019","journal-title":"Bull World Health Organ"},{"key":"pone.0264149.ref002","unstructured":"Centers for Disease Control and Prevention (CDC). 2021. Gonorrhea. Sexually Transmitted Disease Surveillance 2019. https:\/\/www.cdc.gov\/std\/statistics\/2019\/default.htm (Accessed August 6, 2020)."},{"key":"pone.0264149.ref003","first-page":"335","article-title":"Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with men\u2014United States, 2003, and revised recommendations for gonorrhea treatment, 2004","volume":"53","author":"Centers for Disease Control and Prevention","year":"2004","journal-title":"MMWR"},{"issue":"14","key":"pone.0264149.ref004","first-page":"332","article-title":"Update to CDC\u2019s Sexually Transmitted Diseases Treatment Guidelines, 2006: Fluoroquinolones no longer recommended for treatment of gonococcal infection","volume":"56","author":"Centers for Disease Control and Prevention","year":"2007","journal-title":"MMWR"},{"key":"pone.0264149.ref005","first-page":"1911","article-title":"Update to CDC\u2019s treatment guidelines for gonococcal infection, 2020","volume":"50","author":"Centers for Disease Control and Prevention","year":"2020","journal-title":"MMWR"},{"key":"pone.0264149.ref006","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3201\/eid0301.970104","article-title":"Fluoroquinolone resistance in Neisseria gonorrhoeae","volume":"3","author":"JS Knapp","year":"1997","journal-title":"Emerg Infect Dis"},{"key":"pone.0264149.ref007","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/OLQ.0000000000000591","article-title":"Wild-type gyrase A genotype of Neisseria gonorrhoeae predicts in vitro susceptibility to ciprofloxacin: A systematic review of the literature and meta-analysis","volume":"44","author":"LR Allan-Blitz","year":"2017","journal-title":"Sex Transm Dis"},{"key":"pone.0264149.ref008","unstructured":"Tapsall JW. Antimicrobial resistance in Neisseria gonorrhoeae. 2001. World Health Organization. WHO Collaborative Center for STD and HIV publication. Accessed May 6, 2020. http:\/\/www.who.int\/drugresistance\/Antimicrobial_resistance_in_Neisseria_gonorrhoeae.pdf."},{"key":"pone.0264149.ref009","unstructured":"Centers for Disease Control and Prevention (CDC). 2019. Antibiotic Resistance Threats in the United States. Accessed: Feb 23, 2021. https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf."},{"key":"pone.0264149.ref010","unstructured":"World Health Organization (WHO). 2012. Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva: WHO. Accessed January 19, 2022. https:\/\/www.who.int\/reproductivehealth\/publications\/rtis\/9789241503501\/en\/."},{"key":"pone.0264149.ref011","unstructured":"Joint United Nations Programme on HIV\/AIDS (UNAIDS), World Health Organization (WHO). 1999. Sexually transmitted diseases: policies and principles for prevention and care. Geneva; UNAIDS, WHO: UNAIDS\/01.11e. Accessed January 19, 2022. https:\/\/data.unaids.org\/publications\/irc-pub04\/una97-6_en.pdf."},{"key":"pone.0264149.ref012","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3201\/eid2004.131288","article-title":"Ciprofloxacin resistance and gonorrhea incidence rates in 17 cities, United States, 1991\u20132006","volume":"20","author":"HW Chesson","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"pone.0264149.ref013","unstructured":"Centers for Disease Control and Prevention. CDC & FDA AR Bank. Accessed Jan 6, 2021. https:\/\/wwwn.cdc.gov\/ARIsolateBank\/Panel\/PanelDetail?ID=1156."},{"key":"pone.0264149.ref014","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1093\/jac\/dkaa303","article-title":"Utility of MALDI-TOF MS for differentiation of Neisseria gonorrhoeae isolates with dissimilar azithromycin susceptibility profiles","volume":"75","author":"CD Pham","year":"2020","journal-title":"J Antimicro Chemotherpy"},{"key":"pone.0264149.ref015","unstructured":"CLSI. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically\u2014Eleventh Edition: CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute, 2018."},{"key":"pone.0264149.ref016","unstructured":"CLSI. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. CLSI Supplement M100. 31th ed. Wayne, PA: CLSI, 2021."},{"issue":"5","key":"pone.0264149.ref017","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1128\/JCM.02131-13","article-title":"Assessment of Etest\u00ae as an alternative to agar dilution for antimicrobial susceptibility testing of Neisseria gonorrhoeae","volume":"52","author":"H Liu","year":"2014","journal-title":"J Clin Microbiol"},{"key":"pone.0264149.ref018","unstructured":"Centers for Disease Control and Prevention. Laboratory Standard Operating Procedure For Pulsenet Nextera Xt Library Prep And Run Setup For The Illumina Miseq. https:\/\/www.cdc.gov\/pulsenet\/pdf\/PNL32-MiSeq-Nextera-XT.pdf (Accessed May 1, 2020)."},{"key":"pone.0264149.ref019","unstructured":"Centers for Disease Control and Prevention. Profiler version 2.9.2. (Accessed May 7, 2020). https:\/\/amdportal-sams.cdc.gov\/portal\/#\/dashboard."},{"key":"pone.0264149.ref020","unstructured":"Krueger F. 2016. Trim Galore: a wrapper tool around Cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files, with some extra functionality for MspI-digested RRBS-type (Reduced Representation Bisufite-Seq) libraries. http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/trim_galore."},{"key":"pone.0264149.ref021","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"A Bankevich","year":"2012","journal-title":"J Comput Biol"},{"key":"pone.0264149.ref022","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/bioinformatics\/btt086","article-title":"QUAST: quality assessment tool for genome assemblies","volume":"29","author":"A Gurevich","year":"2013","journal-title":"Bioinformatics"},{"key":"pone.0264149.ref023","unstructured":"NCBI. Prokaryotic Genome Annotation Pipeline. https:\/\/www.ncbi.nlm.nih.gov\/genome\/annotation_prok."},{"key":"pone.0264149.ref024","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"T. Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0264149.ref025","doi-asserted-by":"crossref","unstructured":"Kirkcaldy RD, Harvey A, Papp J, del Rio C, Soge OO, Holmes KK, et al. 2016. Neisseria gonorrhoeae antimicrobial susceptibility surveillance- The Gonococcal Isolate Surveillance Project, 27 sites, United States, 2014. https:\/\/www.cdc.gov\/mmwr\/volumes\/65\/ss\/ss6507a1.htm?s_cid=ss6507_w (Accessed Jan 6, 2021).","DOI":"10.15585\/mmwr.ss6507a1"},{"key":"pone.0264149.ref026","unstructured":"Centers for Disease Control and Prevention. Gonococcal Isolate Surveillance Project (GISP). https:\/\/www.cdc.gov\/std\/gisp\/default.htm (Accessed May 8, 2020)."},{"issue":"7","key":"pone.0264149.ref027","doi-asserted-by":"crossref","first-page":"e1002366","DOI":"10.1371\/journal.pmed.1002366","article-title":"Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicine","volume":"14","author":"E Alirol","year":"2017","journal-title":"PLoS Med"},{"key":"pone.0264149.ref028","first-page":"1","article-title":"Reflex detection of ciprofloxacin resistance in Neisseria gonorrhoeae by use of the SpeeDx ResistancePlus GC assay","volume":"59","author":"DYJ Lee","year":"2021","journal-title":"J Clin Microbiol"},{"key":"pone.0264149.ref029","article-title":"Resistance-guided treatment of gonorrhea: A perspective clinical study","author":"JD Klausner","year":"2020","journal-title":"Clin Infect Dis"},{"key":"pone.0264149.ref030","first-page":"1019","article-title":"Ciprofloxacin. An undated review of its pharmacology, therapeutic efficacy, and tolerability","volume":"51","author":"R Davis","year":"1996","journal-title":"Drugs"},{"key":"pone.0264149.ref031","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0924-8579(00)00192-8","article-title":"The fluoroquinolone antibacterials: past, present and future perspectives","volume":"16","author":"PC Appelbaum","year":"2000","journal-title":"Int J Antimicrob Agents"},{"key":"pone.0264149.ref032","doi-asserted-by":"crossref","first-page":"a025320","DOI":"10.1101\/cshperspect.a025320","article-title":"Topoisomerase inhibitors: fluoroquinolone mechanism of action and resistance","volume":"6","author":"DC Hooper","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"pone.0264149.ref033","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/jac\/dkv366","article-title":"A real-time PCR assay for direct characterization of the Neisseria gonorrhoeae GyrA 91 locus associated with ciprofloxacin susceptibility","volume":"71","author":"C Buckley","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"pone.0264149.ref034","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1128\/JCM.01909-06","article-title":"Real-time PCR assay for detection of quinolone-resistant Neisseria gonorrhoeae in urine samples","volume":"45","author":"MJ Siedner","year":"2007","journal-title":"J Clin Microbe"},{"key":"pone.0264149.ref035","unstructured":"Centers for Disease Control and Prevention. (CDC). 2021. Sexually Transmitted Infections Treatment Guidelines, 2021. https:\/\/www.cdc.gov\/std\/treatment-guidelines\/STI-Guidelines-2021.pdf. https:\/\/www.cdc.gov\/std\/treatment-guidelines\/default.htm (Accessed August 16, 2021)."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T18:29:53Z","timestamp":1646936993000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264149"}},"subtitle":[],"editor":[{"given":"Yung-Fu","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264149","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]}}}