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Biomedical subjects

William Eisner

Publications and source records attributed to William Eisner.

6 recordsLinked to original sources

Genetic divergence of Campylobacter fetus strains of mammal and reptile origins.

Campylobacter fetus is a gram-negative bacterial pathogen of both humans and animals. Two subspecies have been identified, Campylobacter fetus subsp. fetus and Campylobacter fetus subsp. venerealis, and there are two serotypes, A and B. To further investigate the genetic diversity among C. fetus strains of different origins, subspecies, and serotypes, we performed multiple genetic analyses by utilizing random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis (PFGE), and DNA-DNA hybridization. All 10 primers used for the RAPD analyses can distinguish C. fetus strains of reptile and mammal origin, five can differentiate between C. fetus subsp. fetus and C. fetus subsp. venerealis strains, and four showed differences between type A and type B isolates from mammals. PFGE with SmaI and SalI digestion showed varied genome patterns among different C. fetus strains, but for mammalian C. fetus isolates, genome size was well conserved (mean, 1.52 +/- 0.06 Mb for SmaI and 1.52 +/- 0.05 Mb for SalI). DNA-DNA hybridization demonstrated substantial genomic-homology differences between strains of mammal and reptile origin. In total, these data suggest that C. fetus subsp fetus strains of reptile and mammal origin have genetic divergence more extensive than that between the two subspecies and that between the type A and type B strains. Combining these studies with sequence data, we conclude that there has been substantial genetic divergence between Campylobacter fetus of reptile and mammal origin. Diagnostic tools have been developed to differentiate among C. fetus isolates for taxonomic and epidemiologic uses.

Animals↗

Differential distribution and expression of Panton-Valentine leucocidin among community-acquired methicillin-resistant Staphylococcus aureus strains.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat worldwide. CA-MRSA strains differ from hospital-acquired MRSA strains in their antibiotic susceptibilities and genetic backgrounds. Using several genotyping methods, we clearly define CA-MRSA at the genetic level and demonstrate that the prototypic CA-MRSA strain, MW2, has spread as a homogeneous clonal strain family that is distinct from other CA-MRSA strains. The Panton-Valentine leucocidin (PVL)-encoding genes, lukF and lukS, are prevalent among CA-MRSA strains and have previously been associated with CA-MRSA infections. To better elucidate the role of PVL in the pathogenesis of CA-MRSA, we first analyzed the distribution and expression of PVL among different CA-MRSA strains. Our data demonstrate that PVL genes are differentially distributed among CA-MRSA strains and, when they are present, are always transcribed, albeit with strain-to-strain variability of transcript levels. To directly test whether PVL is critical for the pathogenesis of CA-MRSA, we evaluated the lysis of human polymorphonuclear leukocytes (PMNs) during phagocytic interaction with PVL-positive and PVL-negative CA-MRSA strains. Unexpectedly, there was no correlation between PVL expression and PMN lysis, suggesting that additional virulence factors underlie leukotoxicity and, thus, the pathogenesis of CA-MRSA.

Bacterial Proteins↗

An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

OBJECTIVE: To describe the epidemiologic and molecular investigations that successfully contained an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU). DESIGN: Isolates of MRSA were typed by pulsed-field gel electrophoresis (PFGE) and S. aureus protein A (spa). SETTING: A level III-IV, 45-bed NICU located in a children's hospital within a medical center. PATIENTS: Incident cases had MRSA isolated from clinical cultures (eg, blood) or surveillance cultures (ie, anterior nares). INTERVENTIONS: Infected and colonized infants were placed on contact precautions, cohorted, and treated with mupirocin. Surveillance cultures were performed for healthcare workers (HCWs). Colonized HCWs were treated with topical mupirocin and hexachlorophene showers. RESULTS: From January to March 2001, the outbreak strain of MRSA, PFGE clone B, was harbored by 13 infants. Three (1.3%) of 235 HCWs were colonized with MRSA. Two HCWs, who rotated between the adult and the pediatric facility, harbored clone C. One HCW, who exclusively worked in the children's hospital, was colonized with clone B. From January 1999 to November 2000, 22 patients hospitalized in the adult facility were infected or colonized with clone B. Spa typing and PFGE yielded concordant results. PFGE clone B was identified as spa type 16, associated with outbreaks in Brazil and Hungary. CONCLUSIONS: A possible route of MRSA transmission was elucidated by molecular typing. MRSA appears to have been transferred from our adult facility to our pediatric facility by a rotating HCW. Spa typing allowed comparison of our institution's MRSA strains with previously characterized outbreak clones.

Cross Infection↗

Evaluation of a multilocus sequence typing system for Staphylococcus epidermidis.

Staphylococcus epidermidis is a significant cause of nosocomial disease. However, the taxonomy of this pathogen, particularly at subspecies level, is unclear. A multilocus sequence typing (MLST) scheme has therefore been investigated as a tool to elucidate taxonomic relationships within this group, based on genetic relatedness. DNA sequences for internal fragments of seven housekeeping genes were compared in 47 geographically and temporally diverse S. epidermidis isolates that were obtained from clinical infections. Twenty-three different allelic profiles were detected; 17 of these were represented by single strains and the largest profile group contained 17 isolates. Diversity of the same collection of isolates was investigated by using PFGE of SmaI-digested genomic DNA to test the discrimination and validity of the MLST approach. Isolates within the largest profile group were resolved into four distinct PFGE clusters on the basis of their SmaI digest patterns. Isolates within other profile groups that contained multiple isolates had matching PFGE SmaI patterns within each group. It appears that MLST is an effective method for grouping S. epidermidis strains at the subspecies level; however, it is not as discriminatory as it has been for other species for which MLST schemes have been established and, used alone, would not be a useful method for epidemiological studies. In addition, it was demonstrated that this method was effective for confirming the identity of S. epidermidis CoNS (coagulase-negative) isolates.

Bacterial Typing Techniques↗

Mutant prevention concentration of garenoxacin (BMS-284756) for ciprofloxacin-susceptible or -resistant Staphylococcus aureus.

The new quinolone garenoxacin (BMS-284756), which lacks a C-6 fluorine, was examined for its ability to block the growth of Staphylococcus aureus. Measurement of the MIC and the mutant prevention concentration (MPC) revealed that garenoxacin was 20-fold more potent than ciprofloxacin for a variety of ciprofloxacin-susceptible isolates, some of which were resistant to methicillin. The MPC for 90% of the isolates (MPC(90)) was below published serum drug concentrations achieved with recommended doses of garenoxacin. These in vitro observations suggest that garenoxacin has a low propensity for selective enrichment of fluoroquinolone-resistant mutants among ciprofloxacin-susceptible isolates of S. aureus. For ciprofloxacin-resistant isolates, the MIC at which 90% of the isolates tested were inhibited was below serum drug concentrations while the MPC(90) was not. Thus, for these strains, garenoxacin concentrations are expected to fall inside the mutant selection window (between the MIC and the MPC) for much of the treatment time. As a result, garenoxacin is expected to selectively enrich mutants with even lower susceptibility.

Anti-Infective Agents↗

mecA-blaZ corepressors in clinical Staphylococcus aureus isolates.

The presence and nucleotide sequences of the two mecA repressors, mecI and blaI, were assessed in 73 clinical Staphylococcus aureus isolates. Isolates with mecI mutations were grouped into unique clonal types based on their spa nucleotide repeat patterns. Forty-three of the 45 (96%) isolates with mutant mecI or with a deletion of mecI contained blaI, while blaI was present in only 21 of 28 (78%) isolates with wild-type mecI (P < 0.05). Among 22 additional isolates that did not contain blaI, all had wild-type mecI sequences. We conclude that oxacillin-resistant S. aureus must have at least one of the two functional mecA regulators.

Bacterial Proteins↗