title: Hypervariability of biofilm formation and oxacillin resistance in a Staphylococcus epidermidis strain causing persistent severe infection in an immunocompromised patient.
abstract: We report on a leukemic patient who suffered from a persistent, generalized, and eventually fatal Staphylococcus epidermidis infection during prolonged aplasia. Over a 6-week period, we isolated a genetically and phenotypically unstable S. epidermidis strain related to an epidemic clone associated with hospital infections worldwide. Strikingly, the strain showed a remarkable degree of variability, with evidence of selection and increasing predominance of biofilm-producing and oxacillin-resistant variants over time. Thus, in the early stages of the infection, the strain was found to generate subpopulations which had spontaneously lost the biofilm-mediating ica locus along with the oxacillin resistance-conferring mecA gene. These deletion mutants were obviously outcompeted by the ica- and mecA-positive wild-type genotype, with the selection and predominance of strongly biofilm-forming and oxacillin-resistant variants in the later stages of the infection. Also, a switch from protein- to polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG)-mediated-biofilm production was detected among ica-positive variants in the course of the infection. The data highlight the impact of distinct S. epidermidis clonal lineages as serious nosocomial pathogens that, through the generation and selection of highly pathogenic variants, may critically determine disease progression and outcome.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Weisser
authors.forename: Sonja M K
authors.initials: SM
authors.lastname: Schoenfelder
authors.forename: Christina
authors.initials: C
authors.lastname: Orasch
authors.forename: Caroline
authors.initials: C
authors.lastname: Arber
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Reno
authors.initials: R
authors.lastname: Frei
authors.forename: Martin
authors.initials: M
authors.lastname: Eckart
authors.forename: Ursula
authors.initials: U
authors.lastname: Flückiger
authors.forename: Wilma
authors.initials: W
authors.lastname: Ziebuhr
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000382:microbiology; D018441:Biofilms / Q000254:growth & development*; D017809:Fatal Outcome; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology* / Q000627:therapeutic use; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000472:pathogenicity; D033581:Stem Cell Transplantation; D055815:Young Adult; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D010068:Oxacillin