The Relationship between Ciprofloxacin Resistance and Genotypic Changes in S. aureus Ocular Isolates
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Non-Synonymous Variations in the Genes of the Ocular Isolates
3.2. Genetic Variations in Quinolone-Associated Genes
3.3. Mutations in the DNA Mismatch Repair System
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Nucleotide Accession
References
- Lowy, F.D. Staphylococcus aureus infections. N. Engl. J. Med. 1998, 339, 520–532. [Google Scholar] [CrossRef]
- Wertheim, H.F.; Melles, D.C.; Vos, M.C.; van Leeuwen, W.; van Belkum, A.; Verbrugh, H.A.; Nouwen, J.L. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect. Dis. 2005, 5, 751–762. [Google Scholar] [CrossRef]
- Azari, A.A.; Barney, N.P. Conjunctivitis: A systematic review of diagnosis and treatment. JAMA 2013, 310, 1721–1729. [Google Scholar] [CrossRef]
- Snyder, C. Infiltrative keratitis with contact lens wear—A review. J. Am. Optom. Assoc. 1995, 66, 160–177. [Google Scholar]
- Suchecki, J.K.; Ehlers, W.H.; Donshik, P.C. Peripheral corneal infiltrates associated with contact lens wear. CLAO J. 1996, 22, 41–46. [Google Scholar]
- Sweeney, D.F.; Jalbert, I.; Covey, M.; Sankaridurg, P.R.; Vajdic, C.; Holden, B.A.; Sharma, S.; Ramachandran, L.; Willcox, M.D.; Rao, G.N. Clinical characterization of corneal infiltrative events observed with soft contact lens wear. Cornea 2003, 22, 435–442. [Google Scholar] [CrossRef]
- Lowy, F.D. Antimicrobial resistance: The example of Staphylococcus aureus. J. Clin. Investig. 2003, 111, 1265–1273. [Google Scholar] [CrossRef]
- Shrivastava, S.; Shrivastava, P.; Ramasamy, J. World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibioti. J. Med. Soc. 2018, 32, 76–77. [Google Scholar] [CrossRef]
- Guo, Y.; Song, G.; Sun, M.; Wang, J.; Wang, Y. Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus. Front. Cell. Infect. Microbiol. 2020, 10, 107. [Google Scholar] [CrossRef] [Green Version]
- Smith, A.; Pennefather, P.M.; Kaye, S.B.; Hart, C.A. Fluoroquinolones: Place in ocular therapy. Drugs 2001, 61, 747–761. [Google Scholar] [CrossRef]
- Alam, M.; Bastakoti, B. Therapeutic Guidelines: Antibiotics. Aust. Prescr. 2015, 38, 137. [Google Scholar] [CrossRef] [Green Version]
- Acar, J.F.; Goldstein, F.W. Trends in bacterial resistance to fluoroquinolones. Clin. Infect. Dis. 1997, 24 (Suppl. S1), S67–S73. [Google Scholar] [CrossRef]
- Ball, P. Emergent resistance to ciprofloxacin amongst Pseudomonas aeruginosa and Staphylococcus aureus: Clinical significance and therapeutic approaches. J. Antimicrob. Chemother. 1990, 26 (Suppl. F), 165–179. [Google Scholar] [CrossRef]
- Shalit, I.; Berger, S.A.; Gorea, A.; Frimerman, H. Widespread quinolone resistance among methicillin-resistant Staphylococcus aureus isolates in a general hospital. Antimicrob. Agents Chemother. 1989, 33, 593–594. [Google Scholar] [CrossRef] [Green Version]
- Werner, N.L.; Hecker, M.T.; Sethi, A.K.; Donskey, C.J. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients. BMC Infect. Dis. 2011, 11, 187. [Google Scholar] [CrossRef] [Green Version]
- Leibovitch, I.; Lai, T.F.; Senarath, L.; Hsuan, J.; Selva, D. Infectious keratitis in South Australia: Emerging resistance to cephazolin. Eur. J. Ophthalmol. 2005, 15, 23–26. [Google Scholar] [CrossRef]
- Ly, C.N.; Pham, J.N.; Badenoch, P.R.; Bell, S.M.; Hawkins, G.; Rafferty, D.L.; McClellan, K.A. Bacteria commonly isolated from keratitis specimens retain antibiotic susceptibility to fluoroquinolones and gentamicin plus cephalothin. Clin. Exp. Ophthalmol. 2006, 34, 44–50. [Google Scholar] [CrossRef]
- Samarawickrama, C.; Chan, E.; Daniell, M. Rising fluoroquinolone resistance rates in corneal isolates: Implications for the wider use of antibiotics within the community. Healthc. Infect. 2015, 20, 128–133. [Google Scholar] [CrossRef]
- Watson, S.; Cabrera-Aguas, M.; Khoo, P.; Pratama, R.; Gatus, B.J.; Gulholm, T.; El-Nasser, J.; Lahra, M.M. Keratitis antimicrobial resistance surveillance program, Sydney, Australia: 2016 Annual Report. Clin. Exp. Ophthalmol. 2019, 47, 20–25. [Google Scholar] [CrossRef] [Green Version]
- Thomas, R.K.; Melton, R.; Asbell, P.A. Antibiotic resistance among ocular pathogens: Current trends from the ARMOR surveillance study (2009–2016). Clin. Optom. 2019, 11, 15–26. [Google Scholar] [CrossRef] [Green Version]
- Afzal, M.; Vijay, A.K.; Stapleton, F.; Willcox, M.D.P. Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions. Antibiotics 2021, 10, 1203. [Google Scholar] [CrossRef]
- Yoshida, H.; Bogaki, M.; Nakamura, M.; Nakamura, S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob. Agents Chemother. 1990, 34, 1271–1272. [Google Scholar] [CrossRef]
- Yoshida, H.; Bogaki, M.; Nakamura, M.; Yamanaka, L.M.; Nakamura, S. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob. Agents Chemother. 1991, 35, 1647–1650. [Google Scholar] [CrossRef] [Green Version]
- Kaatz, G.W.; Seo, S.M. Inducible NorA-mediated multidrug resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 1995, 39, 2650–2655. [Google Scholar] [CrossRef] [Green Version]
- Kaatz, G.W.; Seo, S.M.; Ruble, C.A. Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 1993, 37, 1086–1094. [Google Scholar] [CrossRef] [Green Version]
- Ding, Y.; Onodera, Y.; Lee, J.C.; Hooper, D.C. NorB, an efflux pump in Staphylococcus aureus strain MW2, contributes to bacterial fitness in abscesses. J. Bacteriol. 2008, 190, 7123–7129. [Google Scholar] [CrossRef] [Green Version]
- Truong-Bolduc, Q.C.; Dunman, P.M.; Strahilevitz, J.; Projan, S.J.; Hooper, D.C. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J. Bacteriol. 2005, 187, 2395–2405. [Google Scholar] [CrossRef] [Green Version]
- Truong-Bolduc, Q.C.; Strahilevitz, J.; Hooper, D.C. NorC, a new efflux pump regulated by MgrA of Staphylococcus aureus. Antimicrob. Agents Chemother. 2006, 50, 1104–1107. [Google Scholar] [CrossRef] [Green Version]
- Kaatz, G.W.; Thyagarajan, R.V.; Seo, S.M. Effect of promoter region mutations and mgrA overexpression on transcription of norA, which encodes a Staphylococcus aureus multidrug efflux transporter. Antimicrob. Agents Chemother. 2005, 49, 161–169. [Google Scholar] [CrossRef] [Green Version]
- Truong-Bolduc, Q.C.; Zhang, X.; Hooper, D.C. Characterization of NorR protein, a multifunctional regulator of norA expression in Staphylococcus aureus. J. Bacteriol. 2003, 185, 3127–3138. [Google Scholar] [CrossRef] [Green Version]
- Kaatz, G.W.; McAleese, F.; Seo, S.M. Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein. Antimicrob. Agents Chemother. 2005, 49, 1857–1864. [Google Scholar] [CrossRef] [Green Version]
- McAleese, F.; Petersen, P.; Ruzin, A.; Dunman, P.M.; Murphy, E.; Projan, S.J.; Bradford, P.A. A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob. Agents Chemother. 2005, 49, 1865–1871. [Google Scholar] [CrossRef]
- Huang, J.; O’Toole, P.W.; Shen, W.; Amrine-Madsen, H.; Jiang, X.; Lobo, N.; Palmer, L.M.; Voelker, L.; Fan, F.; Gwynn, M.N.; et al. Novel chromosomally encoded multidrug efflux transporter MdeA in Staphylococcus aureus. Antimicrob. Agents Chemother. 2004, 48, 909–917. [Google Scholar] [CrossRef] [Green Version]
- Yamada, Y.; Shiota, S.; Mizushima, T.; Kuroda, T.; Tsuchiya, T. Functional gene cloning and characterization of MdeA, a multidrug efflux pump from Staphylococcus aureus. Biol. Pharm. Bull. 2006, 29, 801–804. [Google Scholar] [CrossRef] [Green Version]
- Hassanzadeh, S.; Mashhadi, R.; Yousefi, M.; Askari, E.; Saniei, M.; Pourmand, M.R. Frequency of efflux pump genes mediating ciprofloxacin and antiseptic resistance in methicillin-resistant Staphylococcus aureus isolates. Microb. Pathog. 2017, 111, 71–74. [Google Scholar] [CrossRef]
- Yamada, Y.; Hideka, K.; Shiota, S.; Kuroda, T.; Tsuchiya, T. Gene cloning and characterization of SdrM, a chromosomally-encoded multidrug efflux pump, from Staphylococcus aureus. Biol. Pharm. Bull. 2006, 29, 554–556. [Google Scholar] [CrossRef] [Green Version]
- Fàbrega, A.; Madurga, S.; Giralt, E.; Vila, J. Mechanism of action of and resistance to quinolones. Microb. Biotechnol. 2009, 2, 40–61. [Google Scholar] [CrossRef] [Green Version]
- Fournier, B.; Aras, R.; Hooper, D.C. Expression of the multidrug resistance transporter NorA from Staphylococcus aureus is modified by a two-component regulatory system. J. Bacteriol. 2000, 182, 664–671. [Google Scholar] [CrossRef] [Green Version]
- Hooper, D.C. Fluoroquinolone resistance among Gram-positive cocci. Lancet Infect. Dis. 2002, 2, 530–538. [Google Scholar] [CrossRef]
- Ng, E.Y.; Trucksis, M.; Hooper, D.C. Quinolone resistance mutations in topoisomerase IV: Relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus. Antimicrob. Agents Chemother. 1996, 40, 1881–1888. [Google Scholar] [CrossRef] [Green Version]
- Schmitz, F.J.; Higgins, P.G.; Mayer, S.; Fluit, A.C.; Dalhoff, A. Activity of quinolones against gram-positive cocci: Mechanisms of drug action and bacterial resistance. Eur. J. Clin. Microbiol. 2002, 21, 647–659. [Google Scholar] [CrossRef]
- Takenouchi, T.; Ishii, C.; Sugawara, M.; Tokue, Y.; Ohya, S. Incidence of various gyrA mutants in 451 Staphylococcus aureus strains isolated in Japan and their susceptibilities to 10 fluoroquinolones. Antimicrob. Agents Chemother. 1995, 39, 1414–1418. [Google Scholar] [CrossRef]
- Schmitz, F.J.; Jones, M.E.; Hofmann, B.; Hansen, B.; Scheuring, S.; Lückefahr, M.; Fluit, A.; Verhoef, J.; Hadding, U.; Heinz, H.P.; et al. Characterization of grlA, grlB, gyrA, and gyrB mutations in 116 unrelated isolates of Staphylococcus aureus and effects of mutations on ciprofloxacin MIC. Antimicrob. Agents Chemother. 1998, 42, 1249–1252. [Google Scholar] [CrossRef] [Green Version]
- Ferrero, L.; Cameron, B.; Crouzet, J. Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 1995, 39, 1554–1558. [Google Scholar] [CrossRef] [Green Version]
- Blázquez, J. Hypermutation as a factor contributing to the acquisition of antimicrobial resistance. Clin. Infect. Dis. 2003, 37, 1201–1209. [Google Scholar] [CrossRef] [Green Version]
- Giraud, A.; Matic, I.; Radman, M.; Fons, M.; Taddei, F. Mutator bacteria as a risk factor in treatment of infectious diseases. Antimicrob. Agents Chemother. 2002, 46, 863–865. [Google Scholar] [CrossRef] [Green Version]
- Miller, J.H. Spontaneous mutators in bacteria: Insights into pathways of mutagenesis and repair. Annu. Rev. Microbiol. 1996, 50, 625–643. [Google Scholar] [CrossRef]
- Prunier, A.L.; Malbruny, B.; Laurans, M.; Brouard, J.; Duhamel, J.F.; Leclercq, R. High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. J. Infect. Dis. 2003, 187, 1709–1716. [Google Scholar] [CrossRef] [Green Version]
- Modrich, P. Mechanisms and biological effects of mismatch repair. Annu. Rev. Genet. 1991, 25, 229–253. [Google Scholar] [CrossRef]
- Chopra, I.; O’Neill, A.J.; Miller, K. The role of mutators in the emergence of antibiotic-resistant bacteria. Drug Resist. Updates 2003, 6, 137–145. [Google Scholar] [CrossRef]
- O’Neill, A.J.; Chopra, I. Insertional inactivation of mutS in Staphylococcus aureus reveals potential for elevated mutation frequencies, although the prevalence of mutators in clinical isolates is low. J. Antimicrob. Chemother. 2002, 50, 161–169. [Google Scholar] [CrossRef] [Green Version]
- Cuny, C.; Witte, W. In vitro activity of linezolid against staphylococci. Clin. Microbiol. Infect. 2000, 6, 331–333. [Google Scholar] [CrossRef]
- Schmitz, F.J.; Fluit, A.C.; Hafner, D.; Beeck, A.; Perdikouli, M.; Boos, M.; Scheuring, S.; Verhoef, J.; Kohrer, K.; Von Eiff, C. Development of resistance to ciprofloxacin, rifampin, and mupirocin in methicillin-susceptible and -resistant Staphylococcus aureus isolates. Antimicrob. Agents Chemother. 2000, 44, 3229–3231. [Google Scholar] [CrossRef] [Green Version]
- Hsieh, P. Molecular mechanisms of DNA mismatch repair. Mutat. Res. 2001, 486, 71–87. [Google Scholar] [CrossRef]
- Rayssiguier, C.; Thaler, D.S.; Radman, M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 1989, 342, 396–401. [Google Scholar] [CrossRef]
- Afzal, M.; Vijay, A.K.; Stapleton, F.; Willcox, M. Virulence Genes of Staphylococcus aureus Associated With Keratitis, Conjunctivitis, and Contact Lens-Associated Inflammation. Transl. Vis. Sci. Technol. 2022, 11, 5. [Google Scholar] [CrossRef]
- Afzal, M.; Vijay, A.K.; Stapleton, F.; Willcox, M.D.P. Genomics of Staphylococcus aureus Strains Isolated from Infectious and Non-Infectious Ocular Conditions. Antibiotics 2022, 11, 1011. [Google Scholar] [CrossRef]
- Weinstein, M.P.; Lewis, J.S. The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: 30th ed CLSI supplement M100 Clinical and Labortary Stranadrads Institute. J. Clin. Microbiol. 2020, 58, e01864-19. [Google Scholar] [CrossRef]
- Bolger, A.M.; Lohse, M.; Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014, 30, 2114–2120. [Google Scholar] [CrossRef] [Green Version]
- Nurk, S.; Bankevich, A.; Antipov, D.; Gurevich, A.; Korobeynikov, A.; Lapidus, A.; Prjibelsky, A.; Pyshkin, A.; Sirotkin, A.; Sirotkin, Y.; et al. Assembling Genomes and Mini-Metagenomes from Highly Chimeric Reads; Springer: Berlin/Heidelberg, Germany, 2013; Volume 7821. [Google Scholar]
- Seemann, T. Prokka: Rapid prokaryotic genome annotation. Bioinformatics 2014, 30, 2068–2069. [Google Scholar] [CrossRef] [Green Version]
- Ng, P.C.; Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 2001, 11, 863–874. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sanfilippo, C.M.; Hesje, C.K.; Haas, W.; Morris, T.W. Topoisomerase mutations that are associated with high-level resistance to earlier fluoroquinolones in Staphylococcus aureus have less effect on the antibacterial activity of besifloxacin. Chemotherapy 2011, 57, 363–371. [Google Scholar] [CrossRef] [PubMed]
- Blanche, F.; Cameron, B.; Bernard, F.X.; Maton, L.; Manse, B.; Ferrero, L.; Ratet, N.; Lecoq, C.; Goniot, A.; Bisch, D.; et al. Differential behaviors of Staphylococcus aureus and Escherichia coli type II DNA topoisomerases. Antimicrob. Agents Chemother. 1996, 40, 2714–2720. [Google Scholar] [CrossRef] [Green Version]
- de Oliveira, T.L.R.; Cavalcante, F.S.; Chamon, R.C.; Ferreira, R.B.R.; Dos Santos, K.R.N. Genetic mutations in the quinolone resistance-determining region are related to changes in the epidemiological profile of methicillin-resistant Staphylococcus aureus isolates. J. Glob. Antimicrob. Resist. 2019, 19, 236–240. [Google Scholar] [CrossRef] [PubMed]
- Ferrero, L.; Cameron, B.; Manse, B.; Lagneaux, D.; Crouzet, J.; Famechon, A.; Blanche, F. Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: A primary target of fluoroquinolones. Mol. Microbiol. 1994, 13, 641–653. [Google Scholar] [CrossRef]
- Yamagishi, J.; Kojima, T.; Oyamada, Y.; Fujimoto, K.; Hattori, H.; Nakamura, S.; Inoue, M. Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 1996, 40, 1157–1163. [Google Scholar] [CrossRef] [Green Version]
- Costa, S.S.; Junqueira, E.; Palma, C.; Viveiros, M.; Melo-Cristino, J.; Amaral, L.; Couto, I. Resistance to antimicrobials mediated by efflux pumps in Staphylococcus aureus. Antibiotics 2013, 2, 83–99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hardy, K.; Sunnucks, K.; Gil, H.; Shabir, S.; Trampari, E.; Hawkey, P.; Webber, M. Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus. mBio 2018, 9, e00894-18. [Google Scholar] [CrossRef] [Green Version]
- Smits, T.H.M. The importance of genome sequence quality to microbial comparative genomics. BMC Genom. 2019, 20, 662. [Google Scholar] [CrossRef]
Strain | Ocular Condition | Ciprofloxacin Sensitivity | MIC (μg/mL) [21] | gyrA | parC | norB | mgrA |
---|---|---|---|---|---|---|---|
SA112 | USA keratitis | Resistant | 2560 | Ser-84-Leu, Glu-88-Leu | Ser-80-Tyr, Glu-84-Lys | - | - |
SA111 | USA keratitis | 1280 | Ser-84-Leu | Ser-80-Tyr | Leu-140-IIe | - | |
SA113 | USA keratitis | 1280 | Ser-84-Leu | Ser-80-Tyr | Leu-140-IIe | Leu-64-Pro | |
SA101 | USA conjunctivitis | 128 | Ser-84-Leu | Ser-80-Tyr | - | - | |
M43-01 | Australia keratitis | 128 | Ser-84-Leu, Thr-845-Ala, IIe-855-Met | Ser-80-Phe | - | - | |
SA107 | USA keratitis | 64 | Asn-860-Thr | - | Leu-412-IIe Tyr-289-Phe | - | |
M5-01 | Australia keratitis | 64 | - | - | IIe-12-Thr, Ser-331-Thr, Ala-186-Thr | - | |
SA90 | USA conjunctivitis | 64 | Ser-84-Leu | Ser-80-Tyr Glu-84-Lys | - | - | |
SA102 | USA conjunctivitis | 32 | Ser-84-Leu | Ser-80-Phe | - | - | |
SA103 | USA conjunctivitis | 32 | Ser-84-Leu | Ser-80-Tyr | - | - | |
SA114 | USA keratitis | 8 | - | - | Agr-168-Cys | - | |
M71-01 | Australia keratitis | 4 | - | - | - | - | |
SA136 | Australia conjunctivitis | 4 | - | - | IIe-12-Thr, Ser-331-Thr, Ala-186-Thr | - | |
SA31 | niCIE | 4 | - | - | - | - | |
SA86 | USA conjunctivitis | Susceptible | 1 | ||||
SA34 | Australia keratitis | 1 | |||||
SA129 | Australia keratitis | 1 | |||||
M19-01 | Australia keratitis | 1 | |||||
M28-01 | Australia keratitis | 1 | |||||
SA46 | Australia conjunctivitis | 1 | |||||
SA20 | niCIE | 1 | |||||
SA25 | niCIE | 1 | |||||
SA27 | niCIE | 1 | |||||
SA32 | niCIE | 1 | |||||
SA48 | niCIE | 1 |
S. aureus Isolates | Ciprofloxacin Sensitivity | CIP MIC (μg/mL) | MMR Genes and Sites of Mutations | |
---|---|---|---|---|
mutL | mutS | |||
SA112 | Resistant | 2560 | His-347-Tyr | - |
SA111 | 1280 | His-347-Tyr | - | |
SA113 | 1280 | His-347-Tyr | - | |
SA101 | 128 | - | - | |
M43-01 | 128 | - | - | |
SA107 | 64 | - | - | |
M5-01 | 64 | - | - | |
SA90 | 64 | His-347-Tyr | - | |
SA102 | 32 | - | - | |
SA103 | 32 | - | - | |
SA114 | 8 | - | Gln-531-His | |
M71-01 | 4 | His-347-Tyr | - | |
SA136 | 4 | - | - | |
SA31 | 4 | - | Gln-531-His | |
SA86 | Susceptible | 1 | His-347-Tyr | - |
SA34 | 1 | - | Ala-172-Val | |
SA129 | 1 | - | Gln-531-His | |
M19-01 | 1 | Val-583-IIe | - | |
M28-01 | 1 | Val-583-IIe | - | |
SA46 | 1 | - | - | |
SA20 | 1 | - | - | |
SA25 | 1 | His-347-Tyr | - | |
SA27 | 1 | - | Gln-531-His | |
SA32 | 1 | - | - | |
SA48 | 1 | His-347-Tyr | - |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Afzal, M.; Vijay, A.K.; Stapleton, F.; Willcox, M. The Relationship between Ciprofloxacin Resistance and Genotypic Changes in S. aureus Ocular Isolates. Pathogens 2022, 11, 1354. https://doi.org/10.3390/pathogens11111354
Afzal M, Vijay AK, Stapleton F, Willcox M. The Relationship between Ciprofloxacin Resistance and Genotypic Changes in S. aureus Ocular Isolates. Pathogens. 2022; 11(11):1354. https://doi.org/10.3390/pathogens11111354
Chicago/Turabian StyleAfzal, Madeeha, Ajay Kumar Vijay, Fiona Stapleton, and Mark Willcox. 2022. "The Relationship between Ciprofloxacin Resistance and Genotypic Changes in S. aureus Ocular Isolates" Pathogens 11, no. 11: 1354. https://doi.org/10.3390/pathogens11111354