title: Novel Phagocytosis-Resistant Extended-Spectrum β-Lactamase-Producing Escherichia coli From Keratitis.
abstract: OBJECTIVE
  Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are highly antibiotic resistant, and primary ocular infection by ESBL E coli has rarely been reported. A novel mutation conferring phagocytosis resistance would position a strain well to infect the cornea.
  
  
  METHODS
  A woman with recurrent keratitis presented with a corneal ulcer, which was culture positive for ESBL E coli. Resistant to nearly all other antimicrobials, the infection was treated with amikacin and polymyxin B-trimethoprim, and the ulcer resolved over 3 weeks. Analysis of the E coli genome showed it to belong to multilocus sequence type 131 (ST131). This isolate was found to possess a novel deletion in yrfF, an essential regulator of bacterial capsule synthesis. Disruption of yrfF, which confers mucoidy and increased virulence, has not been previously observed in ESBL E coli from any infection site. This novel variant was experimentally proven to cause the mucoid phenotype, and corresponding resistance to phagocytic killing.
  
  
  CONCLUSIONS
  Increased resistance to immune clearance in an ESBL E coli lineage already known for its virulence is an unsettling development. This phenotype, which likely positioned it as an unusual cause of corneal ulcer, can be easily recognized in the laboratory, which should help limit its spread.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts2Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daria
authors.initials: D
authors.lastname: Van Tyne
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Ciolino
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Jay
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts3Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts4Infectious Disease Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marlene L
authors.initials: ML
authors.lastname: Durand
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts2Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D015818:Eye Infections, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D006801:Humans; D007634:Keratitis / Q000188:drug therapy / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects; D014774:Virulence; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases